Attorney Docket No. 35327-522001 WO UREA BIOSENSORS AND USES THEREOF

RELATED APPLICATIONS

This application claims benefit of priority to U.S. Provisional Application No.

62/257,834, filed November 20, 2015 and U.S. Provisional Application No. 62/257,796, filed November 20, 2015, the entire contents of each of which are incorporated herein by reference.

INCORPORATION-BY-REFERENCE OF SEQUENCE LISTING

The contents of the text file named "35327-522001WO_Sequence_Listing.txt", which was created on November 19, 2016 and is 650 KB in size, is hereby incorporated by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates to compositions and methods for detecting and determining the concentration of urea.

BACKGROUND

Urea concentrations are typically measured enzymatically with a urease. Enzyme activity is determined by measuring reaction product (protons, ammonium, and bicarbonate), either colorimetrically in coupled enzyme assays, with ion-selective electrodes, or with another physical technique. Although these assays can perform well, all are sensitive to inhibition of urease activity or alternative sources of product (e.g. pH fluctuations, dissolved C0 ₂ ). Some of these assays require multiple reagents (e.g. coupled enzymes) or multi- component detectors (e.g. membranes and compartments of ion-selective electrodes).

Improved sensors for urea are needed.

SUMMARY OF THE INVENTION

The compositions and methods described herein provide a solution to these and other disadvantages associated with earlier urea sensors.

Provided herein are improved biosensors that rapidly, reliably, and accurately detect and quantify urea with significant advantages over previous systems. The present disclosure Attorney Docket No. 35327-522001 WO provides a biosensor for urea, comprising repoter group that is attached to a urea-binding protein. The ligand comprises urea:

and the ligand-binding protein includes a domain or region(s) of the protein that binds the urea. The domain or region involved in ligand binding is comprised of a plurality of residues, e.g., non-contiguous amino acids of the ligand-binding protein, which are contact points or sites of contact between the ligand and its cognate ligand-binding protein. The binding of urea to the urea-binding domain of the urea-binding protein causes a change in signaling by the reporter group. In various implementations, the biosensor may produce a signal when a urea is bound to the urea binding domain that is not produced (and/or that is different from a signal that is produced) when the urea is absent from the urea binding domain. These biosensors have widespread utility including in clinical, industrial, food and beverage production and storage, and environmental settings.

A reporter group that transduces a detectable signal may be attached to the urea- binding proteins (biosensors) described herein. As used herein, "transduce" means the conversion of ligand occupancy in the binding site of a ligand-binding protein to a detectable signal. Occupancy refers to the state of ligand being bound or not bound to a cognate ligand- binding protein. In embodiments, detectable signal comprises a fluorescent, electrochemical, nuclear magnetic resonance (NMR), or electron paramagnetic resonance (EPR) signal. The reporter group is attached to the urea-binding protein so that a signal transduced by the reporter group when the urea-binding protein is bound to urea differs from a signal transduced by the reporter group when the urea-binding protein is not bound to urea. The proteins may be engineered to include a single cysteine to which the detectable label, e.g., a fluorophore is covalently attached. The biosensors are reagentless in that their monitoring mechanism requires neither additional substrates for a signal to develop, nor measurement of substrate consumption or product generation rates to determine urea concentrations.

In some embodiments, the biosensor proteins include a second fluorophore, thereby permitting ratiometric sensing/detection of an analyte using establishing non-geometrically modulated Forster resonance energy transfer (ngmFRET). Attorney Docket No. 35327-522001 WO

Among the advantages of these fluorophore-containing protein constructs is their high durability. The constructs retain their ability to bind urea, change shape and thus detect the analyte, urea, (a) even when immobilized (directly or indirectly)onto a solid surface such as a bead, plate, or sheet; (b) even after desiccation (and subsequent reconstitution in a physiological buffer solution); (c) even when subjected to ambient conditions, e.g.,

conditions that can be encountered in storage and/or transportation; and (d) even when aged/stored for extended periods of time, e.g., weeks, months, or even years. Thus, the biosensors do not require refrigeration or a cold chain for distribution, permitting a wider range of applicability such as in-the-field use and reducing the cost of the sensor product.

For clinical applications, microliter volumes (e.g., less than 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, or less than 10 μΐ) of a bodily fluid such as blood may be used. Moreover compared to conventional enzyme-based or antibody based assay systems, the results are achieved virtually instantaneously, e.g., 0.1-5 minutes, e.g., 0.1-1 minutes, or within 30-60 seconds. A further advantage is that the sensors consistently and reliably bind to and detect the analyte (urea) in complex fluids such as whole blood, plasma, serum, saliva, urine, and environmental fluids. Thus in a clinical setting, whole blood need not be processed, thereby reducing time and cost of the diagnostic procedure. Alternatively or in addition, the biosensors provided herein may be used to monitor urea levels continuously. In a non- limiting example, one or more biosensors is immobilized at the tip of a thin optical fiber to construct a urea-responsive optode. Such an optode can be introduced into the body (e.g., subcutaneously). The sensor may be in continuous contact with the sample, and excitation and emission light are passed to and from the immobilized sensor, respectively. Fluctuations in the urea sample alter the dynamic equilibrium between the open and closed states of the urea-binding protein, which is transduced into fluctuations of the fluorescent emission signal, by virtue of the sensing mechanism of the conjugated fluorophore. The emitted light intensities may be read by a reader connected to the optode.

In non-clinical situations, e.g., food and beverage composition (e.g, meat, canned food, dairy, nondairy, a fermented food, a fruit, a vegetable, a tuber, a starch, a grain, pasta, yogurt, soup, ice cream, a broth, a puree, a shake, a smoothie, a batter, a condiment, a sauce, a soft drink, a fountain beverage, water, coffee, tea, milk, a dairy-based beverages, soy-based beverage, an almond-based beverage, vegetable juice, fruit juice, a fruit juice-flavored drink, an energy drink, or an alcoholic beverage) production and/or storage, industrial,

environmental (e.g., wetlands, rivers, streams, ponds, marine environments, wells, aquariums, Attorney Docket No. 35327-522001 WO pools, lakes, rivers, brooks, reservoirs, ground water, residential land, commercial/industrial land, agricultural land, or land abutting agricultural land), or commercial settings such as analysis of waste water, food or beverage production, or bioreactor/fermentation monitoring, the samples to be analyzed can be used directly upon sampling without further purification or processing, similarly reducing time and expense of the test. Moreover, the immobilized sensors need not be washed to remove unbound material following contacting the test sample with the sensors, because the unbound material ("contaminants") do not materially affect the production of a precise, reliable detectable assay signal.

Included herein are urea biosensors that produce a dichromatic, ratiometric signal, i.e., the signal is defined as the quotient of the intensities at two independent wavelengths. The advantage of such a signal is that it provides an internally consistent reference. The self- calibrating nature of a ratiometric measurement removes the necessity for carrying out onboard calibration tests prior to each measurement.

Thus, reagentless, fluorescently responsive urea sensors present a number of advantages over enzyme-based biosensors, including elimination of chemical

transformations, elimination of substrate requirements, and self-calibration, which together lead to rapid response times, continuous monitoring capabilities, simple sample-handling, and lower cost due to simplified manufacturing and distribution processes.

Urea-Binding Proteins

Aspects of the present subject matter provide biosensors comprising a ligand-binding protein that binds urea (i.e., a urea-binding protein). Typically, a natural urea-binding protein has a urea dissociation constant (K _d ) of about ΙΟμΜ or less at room temperature. However, urea-binding proteins may be selected, designed, or engineered (e.g., via mutation) to have a different affinity for urea (e.g., to detect higher or lower levels of urea). In various embodiments, a urea-binding protein has a K _d for urea in the millimolar, micromolar, nanomolar, picomolar, or femtomolar range. For example, a urea-binding protein may have a K _d for urea of at least about 0.00001 mM, 0.0001 mM, 0.001 mM, 0.1 mM, 0.5 mM, 1 mM, 2 mM, 3 mM, 4 mM, 5 mM, 6 mM, 7 mM, 8 mM, 9 mM, 10 mM, 15 mM, 20 mM, 25 mM, 50 mM, 75 mM, 100 mM, 125 mM, 150 mM, 175mM, or 200mM, and/or less than about 0.00001 mM, 0.0001 mM, 0.001 mM, 0.1 mM, 0.5 mM, 1 mM, 2 mM, 3 mM, 4 mM, 5 mM, 6 mM, 7 mM, 8 mM, 9 mM, 10 mM, 15 mM, 20 mM, 25 mM, 50 mM, 75 mM, 100 mM, 125 mM, 150 mM, 175mM, or 200mM. In some embodiments, a urea-binding protein has a K _d Attorney Docket No. 35327-522001 WO for urea below (less than about 2 mM), within (about 2 mM to about 7 mM), or above (greater than about 7 mM) the normal range of urea in human blood. See, e.g., Deepak A. Rao; Le, Tao; Bhushan, Vikas (2007). First Aid for the USMLE Step 1 2008 (First Aid for the Usmle Step 1). McGraw-Hill Medical, as well as, Normal Lab Results from Marshal University School of Medicine, the entire content of each of which is incorporated herein by reference.

In various embodiments, the urea-binding protein has a higher affinity (lower Kd) for urea than for acetamide. In various embodiments, the affinity of the urea-binding protein for urea is at least about 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, or 100-fold higher than the affinity of the urea-binding protein for acetamide.

With respect to the present subject matter, Kd is the equilibrium dissociation constant between a ligand-binding protein and its ligand. Kd decreases with increasing affinity, and Kd may be used as an expression of affinity (the lower the value, the higher the affinity). The Kd value relates to the concentration of ligand required for detectable ligand-binding to occur and so the lower the Kd value (lower concentration required), the higher the affinity of the ligand-binding protem for the ligand. The Kd value corresponds to the ligand concentration at which the binding protein is 50% saturated.

Attorney Docket No. 35327-522001 WO

The ligand-binding proteins (as well as biosensors comprising the ligand-binding proteins) provided herein lack enzymatic activity and are not enzymes. As used herein, an "enzyme" is a protein that catalyzes a specific biochemical reaction. The ligand is not chemically altered (i.e., no chemical bond or atom of the ligand is added or removed) by the ligand-binding protein. Thus, when a ligand dissociates from a ligand-binding protein described herein, the ligand contains the same chemical structure it had before it became bound to the ligand-binding protein.

The ligand-binding protein may comprise a naturally occurring protein or a protein that is modified compared to a naturally occurring protein. For example, the ligand-binding protein may comprise one or more mutations compared to a naturally occurring protein. In some embodiments, the naturally occurring protein is a naturally occurring counterpart of the ligand-binding protein (e.g., the ligand-binding protein is a mutant of the naturally occurring counterpart).

A "naturally occurring counterpart" of a mutant polypeptide is a polypeptide produced in nature from which the mutant polypeptide has been or may be derived (e.g., by one or more mutations). For example, the naturally occurring counterpart is an endogenous polypeptide produced by an organism in nature, wherein the endogenous polypeptide typically does not have one or more of the mutations present in the mutant polypeptide. For convenience and depending on context, a naturally occurring counterpart may be referred to herein for the purpose of comparison and to illustrate the location and/or presence of one or more mutations, binding activities, and/or structural features.

As used herein, a "mutation" is a difference between the amino acid sequence of a modified polypeptide/protein and a naturally occurring counterpart. A polypeptide having a mutation may be referred to as a "mutant." Non-limiting examples of mutations include insertions, deletions, and substitutions. However, the term "mutation" excludes (i) the addition of amino acids to the N-teiminus or C-terminus of a polypeptide, and (ii) the omission/deletion/replacement of a polypeptide's signal peptide (e.g., replacement with another signal peptide or with a methionine).

The addition of amino acids to the N-terminus or C-terminus of a protein via a peptide bond may be referred to herein as a "fusion" of the amino acids to the protein. Similarly, an exogenous protein fused to amino acids (e.g., another protein, a fragment, a tag, or a polypeptide moiety) at its N-terminus or C-terminus may be referred to as a "fusion protein." The added amino acids may comprise a non-native polypeptide, e.g., a polypeptide reporter Attorney Docket No. 35327-522001 WO group such as a fluorescent protein, a moiety that facilitates the isolation or modification of a polypeptide, or a moiety that facilitates the attachment of a polypeptide to a substrate or surface. As used herein, "non-native" when referring to the added amino acids (e.g., a

"polypeptide") of a fusion protein indicates that the polypeptide is not naturally part of the protein to which it is fused in the fusion protein. For example, the sequence of a non-native polypeptide ("added amino acids") that is fused to a protein is encoded by an organism other than the organism from which the protein is derived, is not known to be naturally encoded by any organism, or is encoded by a gene other than the wild-type gene that encodes an endogenous version of the protein.

As used herein the term "signal peptide" refers to a short (e.g., 5-30 or 10-100 amino acids long) stretch of amino acids at the N-terminus of a protein that directs the transport of the protein. In various embodiments, the signal peptide is cleaved off during the post- translational modification of a protein by a cell. Signal peptides may also be referred to as "targeting signals," "leader sequences," "signal sequences," "transit peptides," or

"localization signals." In instances where a signal peptide is not defined for a urea-binding protein discussed herein, the signal peptide may optionally be considered to be, e.g., the first 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 40, 50, 60, 70, 80, 90, 100, 5-15, 5-20, 5-25, 5-100, 10-15, 10-20, 10-25, 10-50, 10-100, 25- 50, 25-75, or 25-100 amino acids from the N-terminus of the translated protein (compared to a protein that has not had the signal peptide removed, e.g., compared to a naturally occurring protein).

In some embodiments, the ligand-binding protein comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 1-10, 1-15, 1-20, 5-15, 5-20, 10-25, 10-50, 20-50, 25-75, 25-100 or more mutations compared to a naturally occurring protein while retaining at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5%, or about 100% of the activity of the naturally occurring protein. Mutations include but are not limited to substitutions, insertions, and deletions. Non-limiting examples of ligand-binding proteins may have 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 1-10, 1-15, 1-20, 5-15, 5-20, 10-25, 10-50, 20-50, 25-75, 25-100, or more substitution mutations compared to a naturally occurring protein while retaining at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5%, or about 100% of the activity of the naturally occurring protein. In embodiments, at least one Attorney Docket No. 35327-522001 WO amino acid of the ligand-binding protein has been substituted with a cysteine. Alternatively or in addition, a ligand-binding protein may include one or more mutations that remove a cysteine, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more substitutions or deletions of a cysteine compared to a naturally occurring protein.

Alternatively, the ligand-binding protein is not a mutant. For example, a reporter group is fused to the N-terminus or the C-terminus of the ligand-binding protein.

In some embodiments, the reporter group is conjugated to an amino acid that is no more than about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 40, 50, 60, 70, 80, 90, 100, 5-15, 5-20, 5-25, 5-100, 10-15, 10-20, 10-25, 10- 50, 10-100, 25-50, 25-75, or 25-100 amino acids from the N-terminus or the C-terminus of the ligand-binding protein. In some embodiments, the reporter group is conjugated to an amino acid that is at least about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 40, 50, 60, 70, 80, 90, 100, 5-15, 5-20, 5-25, 5-100, 10-15, 10- 20, 10-25, 10-50, 10-100, 25-50, 25-75, or 25-100 amino acids from the N-terminus or the C- terminus of the ligand-binding protein. In some embodiments, about 5, 6, 7, 8, 9, 10, 11, 12,

13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 40, 50, 60, 70, 80, 90, 100, 5-15, 5-20, 5-25, 5-100, 10-15, 10-20, 10-25, 10-50, 10-100, 25-50, 25-75, or 25-100 amino acids (including or not including the signal peptide) have been deleted (e.g. are absent) from the N-terminus of the protein compared to its naturally occurring counterpart. In some embodiments, less than 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 40, 50, 60, 70, 80, 90, 100, 5-15, 5-20, 5-25, 5-100, 10-15, 10-20, 10- 25, 10-50, 10-100, 25-50, 25-75, or 25-100 amino acids (including or not including the signal peptide) have been deleted (e.g. are absent) from the N-terminus of the protein compared to its naturally occurring counterpart. In some embodiments, about 5, 6, 7, 8, 9, 10, 11, 12, 13,

14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 40, 50, 60, 70, 80, 90, 100, 5-

15, 5-20, 5-25, 5-100, 10-15, 10-20, 10-25, 10-50, 10-100, 25-50, 25-75, or 25-100 amino acids have been deleted (e.g. are absent) from the C-terminus of the protein compared to its naturally occurring counterpart. In some embodiments, less than 5, 6, 7, 8, 9, 10, 11, 12, 13,

14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 40, 50, 60, 70, 80, 90, 100, 5-

15, 5-20, 5-25, 5-100, 10-15, 10-20, 10-25, 10-50, 10-100, 25-50, 25-75, or 25-100 amino acids have been deleted (e.g. are absent) from the C-terminus of the protein compared to its naturally occurring counterpart. Attorney Docket No. 35327-522001 WO

In various embodiments, a ligand-binding protein may comprise a stretch of amino acids (e.g., the entire length of the ligand-binding protein or a portion comprising at least about 50, 100, 200, 250, 300, 350, or 400 amino acids) in a sequence that is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, or 99.5% identical to an amino acid sequence of a naturally occurring protein.

In some embodiments, the mutations are conservative, and the present subject matter includes many ligand-binding proteins in which the only mutations are substitution mutations. In non-limiting examples, a ligand-binding protein has no deletions or insertions compared to a naturally occurring protein (e.g., a naturally occurring counterpart). In non- limiting examples, the urea-binding protein does not comprise a deletion or insertion compared to paAmiC, avUBP, cgUBP, mpUBPl, mhUBP2, bsUBP3, dcUBP4, gtUBP5, ctUBP6, csUBP7, taUBP8, gkUBPIO, psUBPl 1, or teUBP12. Alternatively, a ligand- binding protein may have (i) less than about 5, 4, 3, 2, or 1 inserted amino acids, and/or (ii) less than about 5, 4, 3, 2, or 1 deleted amino acids compared to a naturally occurring protein.

In various embodiments, a naturally occurring protein to which a ligand-binding protein is compared or has been derived (e.g., by mutation, fusion, or other modification) from a prokaryotic ligand-binding protein such as a bacterial ligand-binding protein. For example, the prokaryotic ligand-binding protein is a mutant, fragment, or variant of a natural (i.e., wild-type) bacterial protein. In various embodiments, the bacterial ligand-binding protein is from a thermophilic, mesophilic, or cryophilic prokaryotic microorganism (e.g., a thermophilic, mesophilic, or cryophilic bacterium).

A microorganism is "thermophilic" if it is capable of surviving, growing, and reproducing at temperatures between 41 and 140 °C (106 and 284 °F), inclusive. In various embodiments, a thermophilic organism has an optimal growth temperature between 41 and 140°C, or that is at least about 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, or 140°C. Many thermophiles are archaea. Thermophilic eubacteria are suggested to have been among the earliest bacteria. Thermophiles are found in various geothermally heated regions of the Earth, such as hot springs and deep sea hydrothermal vents, as well as decaying plant matter, such as peat bogs and compost. Unlike other types of microorganisms, thermophiles can survive at much hotter temperatures, whereas other bacteria would be damaged and sometimes killed if exposed to the same temperatures.

Thermophiles maybe classified into three groups: (1) obligate thermophiles; (2) facultative thermophiles; and (3) hyperthermophiles. Obligate thermophiles (also called extreme Attorney Docket No. 35327-522001 WO theimophiles) require such high temperatures for growth, whereas facultative thermophiles (also called moderate thermophiles) can thrive at high temperatures, but also at lower temperatures (e.g. below 50°C). Hyperthermophiles are particularly extreme thermophiles for which the optimal temperatures are above 80°C. Some microorganisms can live at temperatures higher than 100°C at large depths in the ocean where water does not boil because of high pressure. Many hyperthermophiles are also able to withstand other environmental extremes such as high acidity or radiation levels. A compound (e.g., a protein or biosensor) is "thermotolerant" if it is capable of surviving exposure to temperatures above 41°C. For example, in some embodiments a thermotolerant biosensor retains its function and does not become denatured when exposed to a temperature of about 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, or 140°C for at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30 or more minutes. In some embodiments, the thermotolerant compound survives exposure to 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, or 140°C under pressure.

A microorganism is "mesophilic" if it is capable of surviving, growing, and reproducing at temperatures between 20 and 40°C (68 and 104°F), inclusive.

"Psychrophiles" or "cryophiles" are microorganisms that are capable of growth and reproduction in cold temperatures. In various embodiments, a psychrophile is capable of growth and reproduction at a temperature of 10°C or less, e.g., between -20 °C and +10 °C.

In some embodiments, the microbial protein is produced by a bacterial

microorganism, an archaean microorganism, an algal microorganism, a protozoan microorganism, or a fungal microorganism. In non-limiting examples, the microbial protein is produced by a Gram-positive bacterium or a Gram-negative bacterium. In various embodiments, a biosensor comprises a modified (e.g., mutated, fused, and/or conjugated) periplasmic binding protein or a cytoplasmic binding protein.

Aspects of the present subject matter provide a ligand-binding protein with a mutation that alters the interaction of the ligand-binding protein with a ligand (i.e. urea). For example, the ligand-binding protein comprises a mutation that alters the interaction of the ligand- binding protein with the ligand compared to a naturally occurring counterpart. In some embodiments, the ligand-binding protein comprises a mutation that alters the interaction of an amino acid of the ligand-binding protein with a water molecule compared to a naturally occurring counterpart. Attorney Docket No. 35327-522001 WO

In some embodiments, the ligand-binding protein does not comprise a signal peptide. For example, the signal peptide (e.g., that is present in a naturally occurring counterpart) may be replaced with a methionine.

Exemplary implementations relate to a ligand such as urea, wherein the ligand- binding protein comprises a urea-binding protein. For example, the urea-binding protein may comprise a mutant of, a fragment of, or a fusion protein comprising a microbial urea-binding protein. In embodiments, the urea-binding protein is not a mutant or fragment to which a non-native polypeptide has been attached or added. In some embodiments, the ligand- binding protein has an affinity (Kj) for urea within the concentration range of urea in a subject. In certain embodiments, the ligand-binding protein has an affinity (Kj) for urea in the range of about 0.01 mM to about 50 mM, about 0.01 mM to about 25 mM, about 0.01 mM to about 10 mM, about 0.01 mM to about 5 mM, about 0.1 mM to about 50 mM, about 0.1 mM to about 25 mM, about 0.1 mM to about 10 mM, about 0.1 mM to about 5 mM, about 1 mM to about 50 mM, about 1 mM to about 25 mM, about 1 mM to about 10 mM, or about 1 mM to about 5 mM. In various embodiments, the biosensor is capable of detecting urea when urea is present at a concentration of at least about 0.001 mM, 0.1 mM, 0.5 mM, 1 mM, 2 mM, 3 mM, 4 mM, 5 mM, 6 mM, 7 mM, 8 mM, 9 mM, 10 mM, 15 mM, 20 mM, 25 mM, 50 mM, 75 mM, 100 mM, 125 mM, 150 mM, 175mM, or 200mM,. The ratiometric reagentless urea biosensors produce precise measurements over an extended concentration ranges, as noted above, as well as in sample volumes of less than about, e.g., 10 μΐ, 9 μΐ, 8 μΐ, 7 μΐ, 6 μΐ, 5 μΐ, 4 μΐ, 3 μΐ, 2 μΐ, or 1 μΐ. In some embodiments, the volume of sample that is applied to a biosensor or a device comprising a biosensor is less than 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 25, 50, 75, 100, 150, 300, 500, or 1000 μΐ. In some embodiments, the volume is about 0.1 μΐ to about 1000 μΐ, about 0.1 μΐ to about 100 μΐ, about 1 μΐ to about 1000 μΐ, about 1 μΐ to about 10 μΐ, about 1 μΐ to about 100 μΐ, about 1 μΐ to about 50 μΐ, about 10 μΐ to about 50 μΐ, or about 5 μΐ to about 50 μΐ. In some embodiments, the ligand-binding protein comprises a mutation that alters (e.g., increases or decreases) the interaction of the mutant with bound urea compared to a naturally occurring protein (e.g., a microbial urea-binding protein), wherein the interaction is with a portion of the urea selected from the group consisting of a first -NH ₂ group, a second -NH ₂ group, a carbonyl group, or any combination thereof. In non-limiting examples, the ligand-binding protein comprises a mutation that alters (e.g., increases or decreases) the mutant's affinity and/or specificity for urea compared to an unmutated ligand-binding protein (e.g., a microbial urea-binding protein). In non-limiting Attorney Docket No. 35327-522001 WO examples, the mutant's Kd for the ligand is at least 0.001 , 0.01 , 0.1, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 1 10, 120, 130, 140, 150, 160, 170, 180, 190, or 200 mM higher or lower than the unmutated ligand-binding protein. In certain embodiments, the ligand-binding protein comprises a mutation that alters the interaction between the protein and bound urea, a mutation that alters the equilibrium between the open and closed states of the ligand-binding protein, a mutation that alters the interaction between the ligand-binding protein and a reporter group (such as a fluorescent conjugate, e.g., the interaction with Alexa532, or a carbonyl group or a naphthalene ring of a prodan-derived fluorophore such as Acrylodan or Badan), and/or a mutation that impacts indirect interactions that alter the geometry of the ligand binding site. In various embodiments, the mutation does not reduce, or negligibly impacts, the thermostability of the ligand-binding protein. In some

embodiments, the mutation alters the thermostability of the ligand-binding protein by less than about 1 , 2, 3, 4, 5, or 10°C. In some embodiments, the naturally occurring counterpart of the ligand-binding protein is from a Gram-positive bacterium or a Gram-negative bacterium. Non-limiting examples of Gram-negative bacteria include Marinomonas sp., Marinobacter sp., Thermocrinis sp., Synechoccus sp., and Thermosynechococcus sp. Non-limiting examples of Gram-positive bacteria include Bacillus sp., Desulfotomaculum sp., Geobacillus sp., Clostridium sp., Caldicellulosiruptor sp., and Paenibacillus sp.

In various embodiments, the urea-binding protein is purified.

The present subject matter provides a urea-binding protein that is or is a mutant of: an Marinomonas sp. {e.g., M. posidonica ) urea-binding protein; a Marinobacter sp. {e.g., M. adhaerens, M. algicola, M. alkaliphilus, M. antarcticus, M. arcticus, M.aromaticivorans, M. bryozoorum, M. daepoensis, M. daqiaonensis, M. excellens, M.flavimaris, M. gudaonensis, M. guineae, M. halophilus, M. gudaonensis, M. hydrocarbonoclasticus, M. koreensis, M. lacisalsi, M. lipolyticus, M. litoralis, M. lutaoensis, M. maritimus, M. mobilis, M.

nitratireducens, M. oulmenensis, M. pelagius, M. persicus, M. psychrophilus, M. nanhaiticus, M. salarius, M. salicampi, M. salsuginis, M. santoriniensis, M. sediminum, M. segnicrescens, M. shengliensis, M. squalenivorans, M. similis, M. szutsaonensis, M. vinifirmus, M.

xestospongiae, M. zhanjiangensis, or M. zhejiangensis) urea-binding protein; a Bacillus sp. {e.g., B. acidiceler, B. acidicola, B. acidiproducens, B. acidocaldarius, B. acidoterrestris, B. aeolius, B. aerius, B. aerophilus, B. agar adhaerens, B. agri, B. aidingensis, B. akibai, B. alcalophilus, B. algicola, B. alginolyticus, B. alkalidiazotrophicus, B. alkalinitrilicus, B. alkalisediminis, B. alkalitelluris, B. altitudinis, B. alveayuensis, B. alvei, B. Attorney Docket No. 35327-522001 WO amyloliquefaciens, B. a. subsp. amyloliquefaciens, B. a. subsp. plantarum, B. amylolyticus, B. andreesenii, B. aneurinilyticus, B. anthracis, B. aquimaris, B. arenosi, B. arseniciselenatis, B. arsenicus, B. aurantiacus, B. arvi, B. aryabhattai, B. asahii, B. atrophaeus, B.

axarquiensis, B. azotofixans, B. azotoformans, B. badius, B. barbaricus, B. bataviensis, B. beijingensis, B. benzoevorans, B. beringensis, B. berkeleyi, B. beveridgei, B. bogoriensis, B. boroniphilus, B. borstelensis, B. brevis, B. butanolivorans, B. canaveralius, B. carboniphilus, B. cecembensis, B. cellulosilyticus, B. centrosporus, B. cereus, B. chagannorensis, B.

chitinolyticus, B. chondroitinus, B. choshinensis, B. chungangensis, B. cibi, B. circulans, B. clarkii, B. clausii, B. coagulans, B. coahuilensis, B. cohnii, B. composti, B. curdlanolyticus, B. cycloheptanicus, B. cytotoxicus, B. daliensis, B. decisifrondis, B. decolor ationis, B. deserti, B. dipsosauri, B. drentensis, B. edaphicus, B. ehimensis, B. eiseniae, B. enclensis, B.

endophyticus, B. endoradicis, B.farraginis, B.fastidiosus, B.fengqiuensis, B.firmus, B. flexus, B.foraminis, B.fordii, B.formosus, B.fortis, B.fumarioli, B. funiculus, B.fusiformis, B. galactophilus, B. galactosidilyticus, B. galliciensis, B. gelatini, B. gibsonii, B. ginsengi, B. ginsengihumi, B. ginsengisoli, B. globisporus, B. g. subsp. globisporus, B. g. subsp. marinus, B. glucanolyticus, B. gordonae, B. gottheilii, B. graminis, B. halmapalus, B. haloalkaliphilus, B. halochares, B. halodenitrificans, B. halodurans, B. halophilus, B. halosaccharovorans, B. hemicellulosilyticus, B. hemicentroti, B. herbersteinensis, B. horikoshii, B. horneckiae, B. horti, B. huizhouensis, B. humi, B. hwajinpoensis, B. idriensis, B. indicus, B. infantis, B. infernus, B. insolitus, B. invictae, B. iranensis, B. isabeliae, B. isronensis, B.jeotgali, B. kaustophilus, B. kobensis, B. kochii, B. kokeshiiformis, B. koreensis, B. korlensis, B.

kribbensis, B. krulwichiae, B. laevolacticus, B. larvae, B. laterosporus, B. lautus, B. lehensis, B. lentimorbus, B. lentus, B. licheniformis, B. ligniniphilus, B. litoralis, B. locisalis, B.

luciferensis, B. luteolus, B. luteus, B. macauensis, B. macerans, B. macquariensis, B. macyae, B. malacitensis, B. mannanilyticus, B. marisflavi, B. marismortui, B. marmarensis, B.

massiliensis, B. megaterium, B. mesonae, B. methanolicus, B. methylotrophicus, B.

migulanus, B. mojavensis, B. mucilaginosus, B. muralis, B. murimartini, B. mycoides, B. naganoensis, B. nanhaiensis, B. nanhaiisediminis, B. nealsonii, B. neidei, B. neizhouensis, B. niabensis, B. niacini, B. novalis, B. oceanisediminis, B. odysseyi, B. okhensis, B. okuhidensis, B. oleronius, B. oryzaecorticis, B. oshimensis, B. pabuli, B. pakistanensis, B. pallidus, B. pallidus, B. panacisoli, B. panaciterrae, B. pantothenticus, B. parabrevis, B. paraflexus, B. pasteurii, B. patagoniensis, B. peoriae, B. persepolensis, B. persicus, B. pervagus, B.

plakortidis, B. pocheonensis, B. polygoni, B. polymyxa, B. popilliae, B. pseudalcalophilus, B. Attorney Docket No. 35327-522001 WO pseudofirmus, B. pseudomycoides, B. psychrodurans, B. psychrophilus, B.

psychrosaccharolyticus, B. psychrotolerans, B. pulvifaciens, B. pumilus, B.

purgationiresistens, B. pycnus, B. qingdaonensis, B. qingshengii, B. reuszeri, B.

rhizosphaerae, B. rigui, B. runs, B. safensis, B. salarius, B. salexigens, B. saliphilus, B. schlegelii, B. sediminis, B. selenatarsenatis, B. selenitireducens, B. seohaeanensis, B.

shacheensis, B. shackletonii, B. siamensis, B. silvestris, B. simplex, B. siralis, B. smithii, B. soli, B. solimangrovi, B. solisalsi, B. songklensis, B. sonorensis, B. sphaericus, B.

sporothermodurans, B. stearothermophilus, B. stratosphericus, B. subterraneus, B. subtilis, B. s. subsp. inaquosorum, B. s. subsp. spizizenii, B. s. subsp. subtilis, B. taeanensis, B.

tequilensis, B. thermantarcticus, B. thermoaerophilus, B. thermoamylovorans, B.

thermocatenulatus, B. thermocloacae, B. thermocopriae, B. thermodenitrificans, B.

thermoglucosidasius, B. thermolactis, B. thermoleovorans, B. thermophilus, B. thermoruber, B. thermosphaericus, B. thiaminolyticus, B. thioparans, B. thuringiensis, B. tianshenii, B. trypoxylicola, B. tusciae, B. validus, B. vallismortis, B. vedderi, B. velezensis, B.

vietnamensis, B. vireti, B. vulcani, B. wakoensis, B. weihenstephanensis, B. xiamenensis, B. xiaoxiensis, or B. zhanjiangensis) urea-binding protein; a Desulfotomaculum sp. {e.g., D. ruminis, D. nigrificans, D. australicum, D. thermobenzoicum, D. geothermicum, D.

thermocistemum, D. aeronauticum, D. halophilum, D. kuznetsovii, D. thermoacetoxidans, D. thermosapovorans, D. acetoxidans, D. reducens, D. putei, D. luciae, D. gibsoniae, D.

sapomandens, D. alkaliphilum, D. sp. FSB6, D. sp. ASRB-Zg, D. sp. 175, D. sp. 176, D. sp. 171, D. sp. C40-3, D. sp. TPOSR, D. sp. WW1, D. sp. SRB-M, D. sp. Mechichi-2001, D. solfataricum, D. sp. ECP-C5, D. sp. MPNegl, D. sp. Ox39, D. sp. RL50L1, D. alcoholivorax, D. sp. NC402, D. sp. NB401, D. sp. NA401, D. salinum, D. carboxydivorans, D. arcticum, D. thermosubterraneum, D. indicum, D. sp. Lac2, D. sp. CYPl, D. sp. CYP9, D. sp. IS3205, D. sp. Srb55, D. sp. Iso-W2, D. sp. 2, D. hydrothermale, D. sp. ADR22, D. sp. Hbr7, D. sp. JD175, D. sp. JD176, D. sp. DSM 7440, D. sp. DSM 7474, D. sp. DSM 7475, D. sp. DSM 7476, D. sp. DSM 8775, D. sp. csl-2, or D. sp. MJ1) urea-binding protein; a Geobacillus sp. {e.g., G. thermoglucosidasius, G. stearothermophilus, G. jurassicus, G. toebii) urea-binding protein; a Clostridium sp. {e.g., C. absonum, C. aceticum, C. acetireducens, C.

acetobutylicum, C. acidisoli, C. aciditolerans, C. aciduria, C. aerotolerans, C. aestuarii, C. akagii, C. aldenense, C. aldrichii, C. algidicarni, C. algidixylanolyticum, C. algifaecis, C. algoriphilum, C. alkalicellulosi, C. aminophilum, C. aminovalericum, C. amygdalinum, C. amylolyticum, C. arbusti, C. arcticum, C. argentinense, C. asparagiforme, C. Attorney Docket No. 35327-522001 WO aurantibutyricum, C. autoethanogenum, C. baratii, C. barkeri, C. bartlettii, C. beijerinckii, C. bifermentans, C. bolteae, C. bornimense, C. botulinum, C. bowmanii, C. bryantii, C. butyricum, C. cadaveris, C. caenicola, C. caminithermale, C. carboxidivorans, C. carnis, C. cavendishii, C. celatum, C. celerecrescens, C. cellobioparum, C. cellulofermentans, C.

cellulolyticum, C. cellulosi, C. cellulovorans, C. chartatabidum, C. chauvoei, C.

chromiireducens, C. citroniae, C. clariflavum, C. clostridioforme, C. coccoides, C.

cochlearium, C. colletant, C. colicanis, C. colinum, C. collagenovorans, C. cylindrosporum, C. difficile, C. diolis, C. disporicum, C. drakei, C. durum, C. estertheticum, C. estertheticum estertheticum, C. estertheticum laramiense, C. fallax, C. felsineum, C. fervidum, C.

fimetarium, C. formicaceticum, C.frigidicarnis, C.frigoris, C. ganghwense, C. gasigenes, C. ghonii, C. glycolicum, C. glycyrrhizinilyticum, C. grantii, C. haemolyticum, C. halophilum, C. hastiforme, C. hathewayi, C. herbivorans, C. hiranonis, C. histolyticum, C.

homopropionicum, C. huakuii, C. hungatei, C. hydrogeniformans, C. hydroxybenzoicum, C. hylemonae, C.jejuense, C. indolis, C. innocuum, C. intestinale, C. irregulare, C. isatidis, C. josui, C. kluyveri, C. lactatifermentans, C. lacusfryxellense, C. laramiense, C. lavalense, C. lentocellum, C. lentoputrescens, C. leptum, C. limosum, C. litorale, C. lituseburense, C. ljungdahlii, C. lortetii, C. lundense, C. magnum, C. malenominatum, C. mangenotii, C. mayombei, C. methoxybenzovorans, C. methylpentosum, C. neopropionicum, C. nexile, C. nitrophenolicum, C. novyi, C. oceanicum, C. orbiscindens, C. oroticum, C. oxalicum, C. papyrosolvens, C. paradoxum, C. paraperfringens, C. paraputrificum, C. pascui, C.

pasteurianum, C. peptidivorans, C. perenne, C. perfringens, C. pfennigii, C.

phytofermentans, C. piliforme, C. polysaccharolyticum, C. populeti, C. propionicum, C. proteoclasticum, C. proteolyticum, C. psychrophilum, C. puniceum, C. purinilyticum, C. putrefaciens, C. putrificum, C. quercicolum, C. quinii, C. ramosum, C. rectum, C. roseum, C. saccharobutylicum, C. saccharogumia, C. saccharolyticum, C. saccharoperbutylacetonicum, C. sardiniense, C. sartagoforme, C. scatologenes, C. schirmacherense, C. scindens, C.

septicum, C. sordellii, C. sphenoides, C. spiroforme, C. sporogenes, C. sporosphaeroides, C. stercorarium, C. stercorarium leptospartum, C. stercorarium stercorarium, C. stercorarium thermolacticum, C. sticklandii, C. straminisolvens, C. subterminale, C. sufflavum, C.

sulfidigenes, C. symbiosum, C. tagluense, C. tepidiprofundi, C. termitidis, C. tertium, C. tetani, Clostridium tetanomorphum, C. thermaceticum, C. thermautotrophicum, C.

thermoalcaliphilum, C. thermobutyricum, C. thermocellum, C. thermocopriae, C.

thermohydrosulfuricum, C. thermolacticum, C. thermopalmarium, C. thermopapyrolyticum, Attorney Docket No. 35327-522001 WO

C. thermosaccharolyticum, C. thermosuccinogenes, C. thermosulfurigenes, C.

thiosulfatireducens, C. tyrobutyricum, C. uliginosum, C. ultunense, C. villosum, C. vincentii, C. viride, C. xylanolyticum, or C. xylanovorans) urea-binding protein; a Caldicellulosiruptor sp. {e.g., C. acetigenus, C. bescii, C. changbaiensis, C. hydrothermalis, C. kristjanssonii, C. kronotsky ensis, C. lactoaceticus, C. owensensis, or C. saccharolyticus) urea-binding protein; a Thermocrinis sp. (e.g., T. ruber, T. albus, or T. minervae) urea-binding protein; a

Synechoccus sp. (e.g., S. ambiguus, S. arcuatus var. calcicolus, S. bigranulatus, S.

brunneolus S. caldarius, S. capitatus, S. carcerarius, S. elongatus, S. endogloeicus, S.

epigloeicus, S. ferrunginosus, S. intermedins, S. koidzumii, S. lividus, S. marinus, S.

minutissimus, S. mundulus, S. nidulans, S. rayssae, S. rhodobaktron, S. roseo-persicinus, S. roseo-purpureus, S. salinarum, S. salinus, S. sciophilus, S. sigmoideus, S. spongiarum, S. subsalsus, S. sulphuricus, S. vantieghemii, S. violaceus, S. viridissimus, or S. vulcanus) urea- binding protein; a Paenibacillus sp. (e.g., P. agarexedens, P. agaridevorans, P. alginolyticus, P. alkaliterrae, P. alvei, P. amylolyticus, P. anaericanus, P. antarcticus, P. assamensis, P. azoreducens, P. azotofixans, P. barcinonensis, P. borealis, P. brasilensis, P. brassicae, P. campinasensis, P. chinjuensis, P. chitinolyticus, P. chondroitinus, P. cineris, P. cookii, P. curdlanolyticus, P. daejeonensis, P. dendritiformis, P. durum, P. ehimensis, P. elgii, P.

favisporus, P. glucanolyticus, P. glycanilyticus, P. gordonae, P. graminis, P. granivorans, P. hodogayensis, P. illinoisensis, P. jamilae, P. kobensis, P. koleovorans, P. koreensis, P.

kribbensis, P. lactis, P. larvae, P. lautus, P. lentimorbus, P. macerans, P. macquariensis, P. massiliensis, P. mendelii, P. motobuensis, P. naphthalenovorans, P. nematophilus, P.

odorifer, P. pabuli, P. peoriae, P. phoenicis, P. phyllosphaerae, P. polymyxa, P. popilliae, P. pulvifaciens, P. rhizosphaerae, P. sanguinis, P. stellifer, P. terrae, P. thiaminolyticus, P. timonensis, P. tylopili, P. turicensis, P. validus, P. vortex, P. vulneris, P. wynnii, P.

xylanilyticus) urea-binding protein; or a Thermosynechococcus sp. (e.g., T. elongatus or T. vulcanus) urea-binding protein.

In various embodiments, a biosensor comprises a urea-binding protein that is or is a mutant of: a urea-binding protein from Marinomonas posidonica (mpUBPl ; SEQ ID NO: 1 , 12, or 212); a urea-binding protein from Marinobacter hydrocarbanoclasticus (mhUBP2; SEQ ID NO: 2, 13, or 213); a urea-binding protein from Bacillus sp. (bsUBP3; SEQ ID NO: 3, 14, or 214); a urea-binding protein from Desulfotomaculum carboxydivorans (dcUBP4; SEQ ID NO: 4, 15, or 215); a urea-binding protein from Geobacillus thermoglucosidasius (gtUBP5; SEQ ID NO: 5, 16, or 216); a urea-binding protein from Clostridium thermocellum Attorney Docket No. 35327-522001 WO

(ctUBP6; SEQ ID NO: 6, 17, or 217); a urea-binding protein from Caldicellulosiruptor saccharolyticus (csUBP7; SEQ ID NO: 7, 18, or 218); a urea-binding protein from

Thermocrinis albus (taUBP8; SEQ ID NO: 8, 19, or 219); a urea-binding protein from

Geobacillus kaustophilus (gkUBPIO; SEQ ID NO: 9, 20, or 220); a urea-binding protein from Paenibacillus sp. (psUBPl 1 ; SEQ ID NO: 10, 21, or 221); or a urea-binding protein from Thermosynechococcus elongatus (teUBP12; SEQ ID NO: 11, 22, or 222).

Aspects of the present subject matter include a urea-binding protein that is or is a mutant of a protein listed in Table 6, e.g., the protein numbered 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349 in Table 6.

With regard to a defined polypeptide, % identity figures higher or lower than those provided herein will encompass various embodiments. Thus, where applicable, in light of a minimum % identity figure, a polypeptide may comprise an amino acid sequence which is at least 60%, 65%, 70%, 75%, 76%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, or 99.9% identical to the reference SEQ ID NO or to each of the reference SEQ ID NOs. In embodiments, the polypeptide comprises an amino acid sequence that is 100% identical to the reference SEQ ID NO. Where applicable, in light of a maximum % identity to a reference sequence, a Attorney Docket No. 35327-522001 WO polypeptide may comprise an amino acid sequence which is less than 75%, 70%, 65%, 60%, 59%, 58%, 57%, 56%, 55%, 54%, 53%, 52%, 51%, 50%, 49%, 48%, 47%, 46%, 45%, 44%, 43%, 42%, 41%, 40%, 39%, 38%, 37%, 36%, 35%, 34%, 33%, 32%, 31%, 30%, 29%, 28%, 27%, 26%, 25%, 24%, 23%, 22%, 21%, 20%, 19%, 18%, 17%, 16%, or 15% identical to the reference SEQ ID NO or to each of the reference SEQ ID NOs. In certain embodiments, a polypeptide comprises amino acids in a sequence that is preferably at least about 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, or 30% and less than about 75%, 70%, 65%, 60%, 55%, 50%, 45%, 44%, 43%, 42%, 41%, 40%, 39%, 38%, 37%, 36%, 35%, 34%, 33%, 32%, 31%, or 30% identical to the reference SEQ ID NO or to each of the reference SEQ ID NOs. In certain embodiments, a polypeptide comprises amino acids in a sequence that is between about 10% and about 60%, 11% and about 60%, 12% and about 60%, 13% and about 60%, 14% and about 60%, 15% and about 60%, 16% and about 60%, 17% and about 60%, 18% and about 60%, 19% and about 60%, 20% and about 60%, 21% and about 60%, 22% and about 60%, 23% and about 60%, 24% and about 60%, 25% and about 60%, 26% and about 60%, 27% and about 60%, 28% and about 60%, 29% and about 60%, 30% and about 60%, about 25% and about 100%, about 25% and about 95%, about 25% and about 85%, about 25% and about 75%, about 25% and about 70%, about 25% and about 65%, 60%, about 25% and about 55%, about 25% and about 50%, about 25% and about 45%, about 25% and about 44%, about 25% and about 43%, about 25% and about 42%, about 25% and about 41%, about 25% and about 40%, about 25% and about 39%, about 25% and about 38%, about 25% and about 37%, about 25% and about 36%, about 25% and about 35%, about 25% and about 34%, about 25% and about 33%, about 25% and about 32%, about 25% and about 31%, or about 25% and about 30% identical to the reference SEQ ID NO or to each of the reference SEQ ID NOs. Non-limiting examples of reference proteins and amino acid sequences disclosed herein include:

(i) a urea-binding protein from Marinomonas posidonica (mpUBP 1 ; genome, NC_015559, protein, YP_004483096.1 ; SEQ ID NO: 1);

(ii) a urea-binding protein from Marinobacter hydrocarbanoclasticus (mhUBP2; genome, NC_017067, protein, YP_005430828.1 ; SEQ ID NO: 2);

(iii) a urea-binding protein from Bacillus sp. (bsUBP3; genome, NC 017743, protein, YP_006233530.1; SEQ ID NO: 3);

(iv) a urea-binding protein from Desulfotomaculum carboxydivorans (dcUBP4; genome, NC_015565, protein, YP_004496535.1 ; SEQ ID NO: 4); Attorney Docket No. 35327-522001 WO

(v) a urea-binding protein from Geobacillus thermoglucosidasius (gtUBP5; genome, NC_015660, protein, YP_004588319.1; SEQ ID NO: 5);

(vi) a urea-binding protein from Clostridium thermocellum (ctUBP6; genome, NC_009012, protein, YP_001038237.1; SEQ ID NO: 6);

(vii) a urea-binding protein from Caldicellulosiruptor saccharolyticus (csUBP7; genome, NC_009437, protein, YP_001181243.1; SEQ ID NO: 7);

(viii) a urea-binding protein from Thermocrinis albus (taUBP8; genome,

NC_013894, protein, YP_003473480.1; SEQ ID NO: 8);

(ix) a urea-binding protein from Geobacillus kaustophilus (gkUBPIO; genome, NC_006510, protein, YP_147790.1; SEQ ID NO: 9);

(x) a urea-binding protein from Paenibacillus sp. (psUBP 11 ; genome,

NC_013406, protein, YP_003241723.1; SEQ ID NO: 10); and

(xi) a urea-binding protein from Thermosynechococcus elongatus (teUBP12; genome, NC_004113, protein, NP_681910.1; SEQ ID NO: 11).

In some embodiments, the urea-binding protein comprises an amino acid sequence with at least 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 60, 70, 80, 90, or 100% identity to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more urea-binding proteins disclosed herein. In certain embodiments, the urea-binding protein comprises an amino acid sequence with at least 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 60, 70, 80, 90, or 100% identity to Pseudomonas aeruginosa AmiC negative regulator of the amiEBCDRS amidase operon (paAmiC; SEQ ID NO: 202), Anabaena sp. urea-binding protein (avUBP; SEQ ID NO: 226), and/or

Corynebacterium glutamicum urea-binding protein (cgUBP; SEQ ID NO: 227).

The urea-binding proteins disclosed herein may optionally be fused {e.g., at their N- terminal and/or C-terminal ends) to a motif comprising a stretch of amino acids that facilitates the isolation or other manipulation such as conjugation to a moiety or

immobilization on a substrate such as a plastic, a cellulose product such as paper, polymer, metal, noble metal, semi-conductor, or quantum dot {e.g., a fluorescent quantum dot) . A non-limiting example of such a stretch of amino acids has the sequence: GGSHHHHHH (SEQ ID NO: 223). This motif is not required for, is not believed to influence or affect ligand-binding activity or signal transduction, and may be omitted from any ligand-binding protein or biosensor disclosed herein. Additionally, for every sequence disclosed herein that Attorney Docket No. 35327-522001 WO includes GGSHHHHHH (SEQ ID NO: 223), a corresponding sequence that is identical except that it lacks GGSHHHHHH (SEQ ID NO: 223) is also provided and intended to be disclosed. For example, each of SEQ ID NOs: 12-104 (and the non-limiting examples of other proteins used in the experiments disclosed herein) comprises this motif (SEQ ID NO: 223). Alternatively or in addition, a ligand-binding protein may be fused to a non-native polypeptide or "added amino acids" that facilitates the attachment thereof to a surface, such as the surface of a device. In some embodiments, a ligand-binding protein may be fused to a FATT hyperacidic region (SEQ ID NO: 224) and/or a sequence fragment for C3 protease (SEQ ID NO: 228). For every sequence disclosed herein that includes FATT hyperacidic region (SEQ ID NO: 224) and/or a sequence fragment for C3 protease (SEQ ID NO: 228), a corresponding sequence that is identical except that it lacks one or both of these sequences is also provided and intended to be disclosed. For example, SEQ ID NOS: 20-22 comprise these sequences.

In some embodiments, a polypeptide comprises 1, 2, 3, 4, 5, or more substitutions or deletions of a cysteine compared to the naturally occurring counterpart of the polypeptide (i.e., 1, 2, 3, 4, 5, or more native cysteines have been removed), e.g., 1, 2, 3, 4, 5, or more cysteine to alanine substitutions compared to the naturally occurring counterpart of the polypeptide. In some embodiments, all of the cysteines of a polypeptide have been deleted and/or substituted compared to its natural counterpart. In some embodiments, one or more cysteines of a polypeptide have been substituted with an alanine, a serine, or a threonine.

In embodiments, the amino acid sequence of a protein comprises no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, or 50 mutations compared to its naturally occurring counterpart. In some embodiments, less than 50, 45, 40, 35, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, or 2 of the mutations is a deletion or insertion of 1, 2, 3, 4, or 5 or no more than 1, 2, 3, 4, or 5 amino acids. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50 or more of the mutations is a substitution mutation. In certain

embodiments, every mutation to a protein compared to its naturally occurring counterpart is a substitution mutation. In various embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50 or more or all of the mutations to a protein compared to its naturally occurring counterpart is a conservative substitution mutation.

In various embodiments, a polypeptide does not have any insertion or deletion compared to its natural counterpart, other than (optionally) the removal of the signal peptide Attorney Docket No. 35327-522001 WO and/or the fusion of compounds such as another polypeptide at the N-teiminus or C-terminus thereof.

Ligand-Binding Proteins Comprising a Primary Complementary Surface (PCS)

The following BLAST parameters are used to identify sequence homologues of a ligand-binding protein [such as the Pseudomonas aeruginosa AmiC negative regulator of the amiEBCDRS amidase operon (paAmiC) or csUBP7]: (1) Expect threshold is 10.0; (2) Gap cost is Existence: 11 and Extension: 1 ; (3) The Matrix employed is BLOSUM62; (4) The filter for low complexity regions is "on." Such an alignment may be generated using the

ProteinHunter program. The ProteinHunter package always executes BLAST searches, with the following command

"blastall -p blastp -m 8 -b 50000 -d %s -i <INPUT FILE> -o OUTPUT FILE>" where <INPUT FILE> and OUTPUT FILE> specify the input and output files, respectively for a given calculation. This command executes the BLAST alignment program for protein sequences with default parameters, intrinsically set by the program. The BLAST program version is 2.2.24.

Sequence homologues of paAmiC or csUBP7 identified using BLAST may be aligned with paAmiC or csUBP7 using ClustalW to identify homologues that share a PCS with paAmiC or csUBP7 as discussed below.

Aspects of the present subject matter provide ligand-binding proteins that share a PCS with a urea-binding protein disclosed herein. In embodiments, the PCS comprises at least about 5, 6, 7, or 8 amino acid positions used to identify a urea-binding protein.

For example, the PCS of csUBP7 may comprise positions 92, 111, 113, 114, 157, 159, 211, and 238, wherein each position is counted as in csUBP7 (SEQ ID NO: 18 or 218; in which the signal peptide has been replaced with a methionine).

In various embodiments, a protein shares a PCS with csUBP7 if the amino acid sequence of the protein has

(i) S at the position that aligns with position 92 of csUBP7;

(ii) Y at the position that aligns with position 111 of csUBP7;

(iii) V, I, or L at the position that aligns with position 113 of csUBP7; and

(iv) Q at the position that aligns with position 114 of csUBP7,

(v) Y at the position that aligns with position 157 of csUBP7,

(vi) Y or F at the position that aligns with position 159 of csUBP7, Attorney Docket No. 35327-522001 WO

(vii) N at the position that aligns with position 211 of csUBP7, and

(viii) S at the position that aligns with position 238 of csUBP7,

wherein the alignment between csUBP7 (SEQ ID NO: 18 or 218) and the protein is constructed using the ClustalW alignment program.

In another non-limiting example, the PCS of paAmiC may comprise positions 85, 104, 106, 107, 150, 152, 206, and 233, wherein each position is counted as in SEQ ID NO: 202.

In some embodiments, a protein shares a PCS with paAmiC if the amino acid sequence of the protein has

(i) S or T at the position that aligns with position 85 of paAmiC;

(ii) W, Y, or T at the position that aligns with position 104 of paAmiC;

(iii) T, I, Q, V, or S at the position that aligns with position 106 of paAmiC; and

(iv) P, Q, E, F, L, Y, C, or W at the position that aligns with position 107 of

paAmiC,

(v) Y at the position that aligns with position 150 of paAmiC,

(vi) Y, F, V, or W at the position that aligns with position 152 of paAmiC,

(vii) V, N, G, or L at the position that aligns with position 206 of paAmiC, and

(viii) T, S, E, M, A, or C at the position that aligns with position 233 of paAmiC, wherein the alignment between paAmiC (SEQ ID NO: 202) and the protein is constructed using the ClustalW alignment program.

In certain embodiments, a protein shares a PCS with paAmiC if the amino acid sequence of the protein has

(i) S at the position that aligns with position 85 of paAmiC;

(ii) Y at the position that aligns with position 104 of paAmiC;

(iii) T or V at the position that aligns with position 106 of paAmiC; and

(iv) P or Q at the position that aligns with position 107 of paAmiC,

(v) Y at the position that aligns with position 150 of paAmiC,

(vi) Y or F at the position that aligns with position 152 of paAmiC,

(vii) V or N at the position that aligns with position 206 of paAmiC, and

(viii) T or S at the position that aligns with position 233 of paAmiC,

wherein the alignment between paAmiC (SEQ ID NO: 202) and the protein is constructed using the ClustalW alignment program. Attorney Docket No. 35327-522001 WO

In various embodiments, a protein shares a PCS with paAmiC if the amino acid sequence of the protein has

(i) S at the position that aligns with position 85 of paAmiC;

(ii) Y at the position that aligns with position 104 of paAmiC;

(iii) V at the position that aligns with position 106 of paAmiC; and

(iv) Q at the position that aligns with position 107 of paAmiC,

(v) Y at the position that aligns with position 150 of paAmiC,

(vi) Y or F at the position that aligns with position 152 of paAmiC,

(vii) N at the position that aligns with position 206 of paAmiC, and

(viii) S at the position that aligns with position 233 of paAmiC,

wherein the alignment between paAmiC (SEQ ID NO: 202) and the protein is constructed using the ClustalW alignment program.

The ProteinHunter package always executes multiple sequence alignments with the following command

"clustalw -infile=<INPUT FILE> -outfile=<OUTPUTFILE> -align -quiet"

This command executes the CLUSTALW multi-sequence alignment program for protein sequences. There are no user-specified parameter settings that alter the alignment behavior of the program. The CLUSTALW program version is 2.1.

For convenience and depending on context, a position that aligns with a stated position of paAmiC or csUBP7 may be referred to herein as "equivalent" to the stated position.

Exemplary Ligand-Binding Proteins

Various biosensors provided herein comprise urea-binding proteins, such as urea- binding proteins that have altered amino acid sequences compared to their naturally occurring counterparts. In embodiments, such proteins are conjugated to reporter groups. mpUBPl, mhUBP2, bsUBP3, dcUBP4, gtUBP5, ctUBP6, csUBP7, taUBP8, gkUBPlO, psUBPl 1, and teUBP12 are non-limiting reference proteins with respect to urea-binding proteins. An alignment of mpUBPl, mhUBP2, bsUBP3, dcUBP4, gtUBP5, ctUBP6, csUBP7, taUBP8, gkUBPlO, psUBPl 1, and teUBP12 is provided in FIG. 6.

In various embodiments, a urea-binding protein (or its naturally occurring counterpart) comprises Attorney Docket No. 35327-522001 WO

(a) an amino acid sequence that is preferably (i) at least about 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, or 30%, and (ii) less than about 100%, 99%, 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 44%, 43%, 42%, 41%, 40%, 39%, 38%, 37%, 36%, or 35% identical to paAmiC, avUBP, cgUBP, mpUBPl, mhUBP2, bsUBP3, dcUBP4, gtUBP5, ctUBP6, csUBP7, taUBP8, gkUBPIO, psUBPl l, and/or teUBP12;

(b) a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%, 60%, 65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 27 of csUBP7;

(c) a cysteine substitution (compared to a naturally occurring counterpart) within a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%, 60%, 65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 27 of csUBP7;

(d) a stretch of amino acids in the sequence TMXIS (where X is any amino acid, or where X is A) (SEQ ID NO: 203);

(e) a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%, 60%, 65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 43 of csUBP7;

(f) a cysteine substitution (compared to a naturally occurring counterpart) within a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%, 60%, 65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 43 of csUBP7;

(g) a stretch of amino acids in the sequence X^XsX+N (where X] is any amino acid, or where X] is I or V; where X ₂ is any amino acid, or where X ₂ is E or Q; where X ₃ is any amino acid, or where X ₃ is E, Q, or K; and where X4 is any amino acid, or where ¾ is I or Q) (SEQ ID NO: 204);

(h) a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%, 60%, 65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 66 of csUBP7;

(i) a cysteine substitution (compared to a naturally occurring counterpart) within a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%, 60%, Attorney Docket No. 35327-522001 WO

65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 66 of csUBP7;

(j) a stretch of amino acids in the sequence ASX]X ₂ X3X4 (where X] is any amino acid, or where X] is N or D; where X ₂ is any amino acid, or where X ₂ is W or P; where X ₃ is any amino acid, or where X ₃ is P or A; and where X4 is any amino acid, or where X ₃ is T or L) (SEQ ID NO: 205);

(k) a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%, 60%,

65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 92 of csUBP7;

(1) a cysteine substitution (compared to a naturally occurring counterpart) within a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%, 60%,

65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 92 of csUBP7;

(m)a stretch of amino acids in the sequence WTSXSR (where X is any amino acid, or where X is A or V) (SEQ ID NO: 206);

(n) a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%, 60%,

65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 114 of csUBP7;

(o) a cysteine substitution (compared to a naturally occurring counterpart) within a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%, 60%,

65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 114 of csUBP7;

(p) a stretch of amino acids in the sequence YPVQXEG (where X is any amino acid, or where X is F or Y) (SEQ ID NO: 207);

(q) a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%, 60%,

65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 158 of csUBP7;

(r) a cysteine substitution (compared to a naturally occurring counterpart) within a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%, 60%,

65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 158 of csUBP7; Attorney Docket No. 35327-522001 WO

(s) a stretch of amino acids in the sequence YVX ₁ PRTAX ₂ (where X] is any amino acid, or where X] is F or Y; and where X ₂ is any amino acid, or where X ₂ is A or

T) (SEQ ID NO: 208);

(t) a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%, 60%,

65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 186 of csUBP7;

(u) a cysteine substitution (compared to a naturally occurring counterpart) within a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%, 60%,

65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 186 of csUBP7;

(v) a stretch of amino acids in the sequence PX]GX ₂ (where X] is any amino acid, or where X] is L or F; and where X ₂ is any amino acid, or where X ₂ is H, N, or G)

(SEQ ID NO: 209);

(w)a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%, 60%,

65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 211 of csUBP7;

(x) a cysteine substitution (compared to a naturally occurring counterpart) within a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%, 60%,

65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 211 of csUBP7;

(y) a stretch of amino acids in the sequence TX _! NGDX ₂ NV (where X] is any amino acid, or where X] is L or I; and where X ₂ is any amino acid, or where X ₂ is S or

A) (SEQ ID NO: 210);

(z) a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%, 60%,

65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 239 of csUBP7;

(aa) a cysteine substitution (compared to a naturally occurring counterpart) within a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%, 60%,

65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 239 of csUBP7;

(bb) a stretch of amino acids in the sequence SX _! X ₂ EX ₃ E (where X] is any amino acid, or where X] is I or V; where X ₂ is any amino acid, or where X ₂ is A or G; and where X ₃ is any amino acid, or where X ₃ is E or Q) (SEQ ID NO: 211); Attorney Docket No. 35327-522001 WO

(cc) a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%,

60%, 65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 278 of csUBP7;

(dd) a cysteine substitution (compared to a naturally occurring counterpart) within a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%, 60%,

65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 278 of csUBP7;

(ee) a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%,

60%, 65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 288 of csUBP7;

(ff) a cysteine substitution (compared to a naturally occurring counterpart) within a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%, 60%,

65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 288 of csUBP7;

(gg) a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%,

60%, 65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 329 of csUBP7;

(hh) a cysteine substitution (compared to a naturally occurring counterpart) within a stretch of at least 5, 10, or 20 amino acids having at least about 50%, 55%, 60%,

65%, 75%, 80%, 85%, 90%, or 95% identity to a stretch of consecutive amino acids including position 329 of csUBP7;

(ii) no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 15 deleted or inserted amino acids compared to csUBP7, not including amino acids added to the N-terminus or C- terminus of the polypeptide compared to its natural counterpart, and including or not including the signal peptide of the natural counterpart of the polypeptide; (jj) at least 5, 6, 7, 8, 9, 10, or 11, or exactly 5, 6, 7, 8, 9, 10, or 11 a-helices; and/or (kk) at least 10, 11, 12, 13, or 14 β-strands or exactly 10, 11, 12, 13, or 14 β- strands.

In embodiments, two or more or each of features (a)-(kk) above occurs in the polypeptide in the order listed above as the amino acid sequence of the polypeptide is viewed or read from the N-terminus to the C-terminus (with additional features and/or amino acid sequences therebetween). For example, the polypeptide may have an N-terminus, followed by feature (b), (c), or (d), followed by feature (e), (f), or (g), followed by feature (h), (i), or Attorney Docket No. 35327-522001 WO

(j), followed by feature (k), (1), or (m), followed by feature (n), (o), or (p), followed by feature (q), (r), or (s), followed by feature (t), (u), or (v), followed by feature (w), (x), or (y), followed by feature (z), (aa), or (bb), followed by feature (cc) or (dd), followed by feature (ee) or (ff), followed by feature (gg) or (hh), followed by the C-terminus.

As used herein when referring to the order of features in an amino acid read from the N terminus to the C-terminus, a first feature is "followed by" a second feature when the second feature occurs after the first feature in the amino acid sequence. The words "followed by" do not require that the second feature immediately follow or be close to the first feature. For example, the N-terminus is followed by the C-terminus.

The features listed above are not limiting and may be combined with any other relevant features disclosed herein, including those listed below.

In some embodiments the polypeptide comprises the following sequence:

T IKVG ! LHSLSGTMAI SEVSLK#AE $ $A ! EE INXXGGVLGKKIEP ! ! EDGAS #WPTFA#K AXKLLQX#KVAX ! FGGWT S AS RKAML P WEXNNGL $ F Y PVQ % EGXE S S PN ! FYTGAXPNQ QIVPAVXWLLX#XGXKXFFLXGSDYV% PRTANKI IKAQLKAXGGXXXXXGE#YT PLGHT # YST ! ! XKIKXXXXKPDXXV ! FNTLNGDSNVAF%K# $KDAGIXXXDXPVMSVS ! AE#E IXG I GXXXLXGHLAXWNY %QSX# TPENKEF ! XKYKXKYGXDXRVTXDP IEAX%XXVX$WAXAV XKAGSXDXVDKVKXAAXGXEFXAPXGXVKIXGXNQHLXKTVRIGE I QX#GQFKEVWXSGX P ! XP# PYLKXYXWAKGL

wherein each

X is, individually, any amino acid or is absent,

! is, individually, I or V,

$ is, individually, L or M,

% is, individually, F or Y, and

# is, individually, N, D, Q, or E.

In a non-limiting example, the urea-binding polypeptide comprises an N-teiminal domain and a C-terminal domain connected by a flexible hinge, with the urea-binding site (the urea-binding domain) located in the cleft between the N-terminal and the C-terminal domain.

In some embodiments, the urea-binding polypeptide comprises, from the N-terminus to the C-terminus, a first β-strand (βΐ), followed by a first a-helix (al), followed by a second β-strand (β2), followed by a second a-helix (a2), followed by a third β-strand (β3), followed by a third a-helix (a3), followed by a fourth β-strand (β4), followed by a fifth β-strand (β5), Attorney Docket No. 35327-522001 WO followed by a fourth a-helix (a4), followed by a sixth β-strand (β6), followed by a fifth a- helix (a5), followed by a seventh β-strand (β7), followed by a sixth a-helix (a6), followed by an eighth β-strand (β8), followed by a seventh a-helix (a7), followed by a ninth β-strand (β9), followed by an eighth a-helix (a8), followed by a tenth β-strand (βΐθ), followed by a ninth a- helix (a9), followed by a tenth a-helix (alO), followed by an eleventh a-helix (al 1), followed by an eleventh β-strand (βΐ 1), followed by a twelfth β-strand (β12), followed by a thirteenth β-strand (β13) followed by a fourteenth β-strand (β14). In some embodiments, the polypeptide comprises (i) 1, 2, or 3 amino acid substitutions between βΐ and al; (ii) 1, 2, or 3 amino acid substitutions between β2 and a2; (iii) 1, 2, or 3 amino acid substitutions in a2; (iv) 1, 2, or 3 amino acid substitutions between β3 and a3; (v) 1, 2, or 3 amino acid substitutions in a3; (vi) 1, 2, or 3 amino acid substitutions between β7 and a6; (vii) 1, 2, or 3 amino acid substitutions in β6; (viii) 1, 2, or 3 amino acid substitutions in β4; (ix) 1, 2, or 3 amino acid substitutions between the β4 and β5; (x) 1, 2, or 3 amino acid substitutions in a5; (xi) 1, 2, or 3 amino acid substitutions between β8 and a7; and/or (xii) 1, 2, or 3 amino acid substitutions between β9 and a8. In some embodiments, the substitutions are conservative substitutions. In various embodiments, one or more amino acids is substituted to cysteine compared to a naturally occurring protein.

Beta sheets consist of beta strands (also β-strand) connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet. A β-strand is a stretch of polypeptide chain, e.g. 3 to 20 amino acids long, with backbone in an extended conformation.

Alpha-helical and β-strand segments assignments are calculated from a three- dimensional protein structure as follows, and as described in C.A.F. Andersen, B. Rost, 2003, Structural Bioinformatics, 341-363, P.E. Bourne, ed., Wiley, the entire content of which is incorporated herein by reference. First for a given residue, i, the backbone trace angle, r, is calculated, defined as the dihedral angle between the four successive C _a atom positions of residues in the linear protein sequence i, i+2, i+3. These values are calculated for all residues. Second, the residues that form backbone hydrogen bonds with each other are recorded. A hydrogen bond is scored if the distance between the backbone amide nitrogen and carbonyl oxygen of two different residues in the protein is calculated to be 2.5A or less, and if the calculated angle between the nitrogen, its amide proton, and the carbonyl is greater than 120°. A residue is deemed to be in an a-helix, if 35 < τ < 65 , and it makes a backbone hydrogen bond with its ί ^' +4 ^Λ neighbor in the linear amino acid sequence. It is deemed to be Attorney Docket No. 35327-522001 WO in a β-strand, if the absolute t value falls in the interval 120 < |r| < 180 and if it makes at least one hydrogen bond with another residue with the same rvalue range. Alpha-helical segments comprise at least four residues; β-strand residues comprise at least three residues.

In various embodiments, the C _a root-mean-square deviation (RMSD) between the backbone of the urea-binding polypeptide and paAmiC, avUBP, cgUBP, mpUBPl, mhUBP2, bsUBP3, dcUBP4, gtUBP5, ctUBP6, csUBP7, taUBP8, gkUBPlO, psUBPl l, and/or teUBP12 is, e.g., between about 0-3 A, 0-1 A, 0-1.5 A, 0-2 A, 0.1-3 A, 0.5-1 A, 0.5-1.5 A, or 0.5-2 A, or less than about 0.1 A, 0.2 A, 0.3 A, 0.4 A, 0.5 A, 0.6 A, 0.7 A, 0.8 A, 0.9 A, 1.0 A, 1.5 A, 1.6 A, 1.7 A, 1.8 A, 1.9 A, 2.0 A, 2.5 A, or 3 A. In some embodiments, the C„ RMSD between the N-terminal domain (i.e., the portion of the protein at the N-terminal side of the binding domain hinge) backbone of the urea-binding polypeptide and the

corresponding domain of paAmiC, avUBP, cgUBP, mpUBPl, mhUBP2, bsUBP3, dcUBP4, gtUBP5, ctUBP6, csUBP7, taUBP8, gkUBPlO, psUBPl 1, and/or teUBP12 is, e.g., between about 0-3 A, 0-1 A, 0-1.5 A, 0-2 A, 0.1-3 A, 0.5-1 A, 0.5-1.5 A, or 0.5-2 A, or less than about 0.1 A, 0.2 A, 0.3 A, 0.4 A, 0.5 A, 0.6 A, 0.7 A, 0.8 A, 0.9 A, 1.0 A, 1.5 A, 1.6 A, 1.7 A, 1.8 A, 1.9 A, 2.0 A, 2.5 A, or 3 A. In certain embodiments, the C„ RMSD between the C- terminal domain (i.e., the portion of the protein at the C-terminal side of the binding domain hinge) backbone of the urea-binding polypeptide and the corresponding domain of paAmiC, avUBP, cgUBP, mpUBPl, mhUBP2, bsUBP3, dcUBP4, gtUBP5, ctUBP6, csUBP7, taUBP8, gkUBPlO, psUBPl 1, and/or teUBP12 is, e.g., between about 0-3 A, 0-1 A, 0-1.5 A, 0-2 A, 0.1-3 A, 0.5-1 A, 0.5-1.5 A, or 0.5-2 A, or less than about 0.1 A, 0.2 A, 0.3 A, 0.4 A, 0.5 A, 0.6 A, 0.7 A, 0.8 A, 0.9 A, 1.0 A, 1.5 A, 1.6 A, 1.7 A, 1.8 A, 1.9 A, 2.0 A, 2.5 A, or 3 A. Non-limiting considerations relating to the sequence and structural differences between homologous proteins are discussed in Chothia and Lesk (1986) The EMBO Journal,

5(4):823-826, the entire content of which is incorporated herein by reference.

Non-limiting examples of urea-binding polypeptides that are useful in biosensors provided herein include avUBP, cgUBP, mpUBPl, mhUBP2, bsUBP3, dcUBP4, gtUBP5, ctUBP6, csUBP7, taUBP8, gkUBPlO, psUBPl 1, and teUBP12. In embodiments, a biosensor comprises a modified avUBP, cgUBP, mpUBPl, mhUBP2, bsUBP3, dcUBP4, gtUBP5, ctUBP6, csUBP7, taUBP8, gkUBPlO, psUBPl 1, or teUBP12 polypeptide having an amino acid substitution compared to its naturally occurring counterpart, such that the polypeptide has a cysteine at position 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, Attorney Docket No. 35327-522001 WO

22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, or 400, or any combination of 1, 2, 3, 4, or 5 thereof, wherein the position corresponds a SEQ ID NO disclosed herein for avUBP, cgUBP, mpUBPl, mhUBP2, bsUBP3, dcUBP4, gtUBP5, ctUBP6, csUBP7, taUBP8, gkUBPIO, psUBPl 1, or teUBP12. In embodiments, the cysteine is conjugated to a reporter group.

In various embodiments, a biosensor comprises a modified mpUBPl . In non-limiting examples, the modified mpUBPl may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: T12X, M13X, S16X, E29X, S51X, L55X, W76X, T77X, S78X, V79X, R81X, Y97X, V99X, Q100X, Y101X, E102X, Y144X, V145X, Y146X, F175X, N204X, S231X, E234X, K269X, Y273X, N282X, and T323X, where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in mpUBPl with the signal peptide replaced with a methionine (SEQ ID NO: 12 or 212). The sequence for mpUBPl (SEQ ID NO: 12 or 212) comprises C75A, C385A, and C395A mutations. In some embodiments, the modified mpUBPl comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, Attorney Docket No. 35327-522001 WO

16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, or 27 of the following substitutions: T12C, M13C, S16C, S16I, E29Q, S51C, L55C, W76C, T77C, S78C, S78A, V79C, R81C, Y97A, Y97C, V99A, V99T, V99N, V99Q, V99H, Q100C, Q1004A, Q100S, Q100N, Q100A, Q100D, Q100E, Q100H, Q100T, Q100Y, Q100M, Q100L, Y101C, E102C, E102Q, E102D, E102A, Y144A, Y144C, V145C, Y146A, Y146C, F175C, N204A, N204Q, N204S, N204D, N204E, N204H, N204T, N204L, N204C, S231A, S231N, S231Q, S231H, S231C, E234A, K269N, Y273M, N282S, and T323G.

In various embodiments, a biosensor comprises a modified mhUBP2. In non-limiting examples, the modified mhUBP2 may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: T12X, M13X, S16X, E29X, S51X, L55X, W76X, T77X, S78X, V79X, R81X, Y97X, V99X, Q100X, Y101X, E102X, Y144X, V145X, Y146X, F175X, N204X, S231X, E234X, A269X, Y273X, N282X, and T323X, where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in mhUBP2with the signal peptide replaced with a methionine (SEQ ID NO: 13 or 213). The sequence for mhUBP2 (SEQ ID NO: 13 or 213) comprises C385A and C395A mutations. In some embodiments, the modified mhUBP2 comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, or 27 of the following substitutions: T12C, M13C, S16C, S16I, E29Q, S51C, L55C, W76C, T77C, S78C, S78A, V79C, R81C, Y97A, Y97C, V99A, V99T, V99N, V99Q, V99H, Q100C, Q1004A, Q100S, Q100N, Q100A, Q100D, Q100E, Q100H, Q100T, Q100Y, Q100M, Q100L, Y101C, E102C, E102Q, E102D, E102A, Y144A, Y144C, V145C, Y146A, Y146C, F175C, N204A, N204Q, N204S, N204D, N204E, N204H, N204T, N204L, N204C, S231A, S231N, S231Q, S231H, S231C, E234A, A269N, Y273M, N282S, and T323G.

In various embodiments, a biosensor comprises a modified bsUBP3. In non-limiting examples, the modified bsUBP3 may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: T12X, M13X, S16X, Q29X, S51X, T55X, W76X, T77X, S78X, A79X, R81X, Y97X, V99X, Q100X, Y101X, E102X, Y143X, V144X, F145X, L172X, N197X, S224X, E227X, N262X, M266X, S274X, and G315X, where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in bsUBP3 with the signal peptide replaced with a methionine (SEQ ID NO: 14 or 214). In some embodiments, the modified bsUBP3 comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, Attorney Docket No. 35327-522001 WO

21, 22, 23, 24, 25, 26, or 27 of the following substitutions: T12C, M13C, S16C, S16I, Q29E, S51C, T55C, W76C, T77C, S78C, S78A, A79C, R81C, Y97A, Y97C, V99A, V99T, V99N, V99Q, V99H, Q100C, Q100A, Q100S, Q100N, Q100A, Q100D, Q100E, Q100H, Q100T, Q100Y, Q100M, Q100L, Y101C, E102C, E102Q, E102D, E102A, Y143A, Y143C, V144C, F145A, F145C, L172C, N197A, N197Q, N197S, N197D, N197E, N197H, N197T, N197L, N197C, S224A, S224N, S224Q, S224H, S224C, E227A, N262K, M266K, S274D, and G315E.

In various embodiments, a biosensor comprises a modified dcUBP4. In non-limiting examples, the modified dcUBP4 may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: T14X, M15X, S18X, E31X, S53X, T57X, W78X, T79X, S80X, A81X, R83X, Y99X, V101X, Q102X, Y103X, E104X, Y145X, V146X, F147X, L174X, N199X, S226X, E229X, K264X, K268X, D276X, and E317X, where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in dcUBP4 with the signal peptide replaced with a methionine (SEQ ID NO: 15 or 215). In some embodiments, the modified dcUBP4 comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, or 27 of the following substitutions: T14C, M15C, S18C, S18I, E31Q, S53C, T57C, W78C, T79C, S80C, S80A, A81C, R83C, Y99A, Y99C, V101A, V101T, V101N, V101Q, V101H, Q102C, Q102A, Q102S, Q102N, Q102A, Q102D, Q102E, Q102H, Q102T, Q102Y, Q102M, Q102L, Y103C, E104C, E104Q, E104D, E104A, Y145A, Y145C, V146C, F147A, F147C, L174C, N199A, N199Q, N199S, N199D, N199E, N199H, N199T, N199L, N199C, S226A, S226N, S226Q, S226H, S226C, E229A, K264N, K268M, D276S, and E317G.

In various embodiments, a biosensor comprises a modified gtUBP5. In non-limiting examples, the modified gtUBP5 may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: T36X, M37X, S40X, E53X, S75X, T79X, W100X, T101X, S102X, A103X, R105X, Y121X, V123X, Q124X, Y125X, E126X, Y167X, V168X, F169X, L196X, N221X, S248X, E251X, K286X, K290X, D298X, and G339X, where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in gtUBP5 with the signal peptide replaced with a methionine (SEQ ID NO: 16 or 216). In some embodiments, the modified gtUBP5 comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, or 27 of the following substitutions: T36C, M37C, S40C, S40I, E53Q, Attorney Docket No. 35327-522001 WO

S75C, T79C, W100C, T101C, S102C, S102A, A103C, R105C, Y121A, Y121C, V123A, V123T, V123N, V123Q, V123H, Q124C, Q124A, Q124S, Q124N, Q124A, Q124D, Q124E, Q124H, Q124T, Q124Y, Q124M, Q124L, Y125C, E126C, E126Q, E126D, E126A, Y167A, Y167C, V168C, F169A, F169C, L196C, N221A, N221Q, N221S, N221D, N221E, N221H, N221T, N221L, N221C, S248A, S248N, S248Q, S248H, S248C, E251A, K286N, K290M, D298S, and G339E.

In various embodiments, a biosensor comprises a modified ctUBP6. In non-limiting examples, the modified ctUBP6 may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: T31X, M32X, S35X, E48X, S70X, T74X, C94X, W95X, T96X, S97X, A98X, R100X, Yl 16X, VI 18X, Ql 19X, Y120X, E121X, Y162X, V163X, F164X, L191X, N216X, C240X, S243X, E246X, K281X, K285X, D293X, and E334X, where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in ctUBP6 with the signal peptide replaced with a methionine (SEQ ID NO: 17 or 217). In some

embodiments, the modified ctUBP6 comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 of the following substitutions: T31C, M32C, S35C, S35I, E48Q, S70C, T74C, C94A, W95C, T96C, S97C, S97A, A98C, R100C, Yl 16A, Yl 16C, VI 18A, VI 18T, VI 18N, VI 18Q, VI 18H, Ql 19C, Ql 19A, Ql 19S, Ql 19N, Ql 19A, Ql 19D, Ql 19E, Ql 19H, Ql 19T, Ql 19Y, Ql 19M, Ql 19L, Y120C, E121C, E121Q, E121D, E121A, Y162A, Y162C, V163C, F164A, F164C, L191C, N216A, N216Q, N216S, N216D, N216E, N216H, N216T, N216L, N216C, C240A, S243A, S243N, S243Q, S243H, S243C, E246A, K281N, K285M, D293S, and E334G.

In various embodiments, a biosensor comprises a modified csUBP7. In non-limiting examples, the modified csUBP7 may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: T26X, M27X, S30X, E43X, S65X, T69X, W90X, T91X, S92X, A93X, R95X, Yl 1 IX, VI 13X, Ql 14X, Yl 15X, El 16X, Y157X, V158X, F159X, L186X, N21 IX, S238X, E241X, K276X, K280X, D288X, and E329X, where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in csUBP7 with the signal peptide replaced with a methionine (SEQ ID NO: 18 or 218). The sequence for csUBP7 (SEQ ID NO: 18 or 218) comprises a C89A mutation. In some embodiments, the modified csUBP7 comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, or 27 of the following substitutions: T26C, M27C, S30C, S30I, E43Q, S65C, Attorney Docket No. 35327-522001 WO

T69C, W90C, T91C, S92C, S92A, A93C, R95C, Yl 11A, Yl 11C, VI 13A, VI 13T, VI 13N, VI 13Q, VI 13H, Ql 14C, Ql 14A, Ql 14S, Ql 14N, Ql 14A, Ql 14D, Ql 14E, Ql 14H, Ql 14T, Ql 14Y, Ql 14M, Ql 14L, Yl 15C, El 16C, El 16Q, El 16D, El 16A, Y157A, Y157C, V158C, F159A, F159C, L186C, N211A, N211Q, N21 IS, N21 ID, N21 IE, N211H, N21 IT, N211L, N211C, S238A, S238N, S238Q, S238H, S238C, E241A, K276N, K280M, D288S, and E329G.

In various embodiments, a biosensor comprises a modified taUBP8. In non-limiting examples, the modified taUBP8 may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: T47X, M48X, S51X, E64X, S86X, T90X, Wl 1 IX, Tl 12X, SI 13X, Al 14X, Rl 16X, Y132X, V134X, Q135X, F136X, E137X, Y178X, V179X, F180X, L207X, N232X, S259X, E262X, A297X, K301X, T309X, and F351X, where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in taUBP8 with the signal peptide replaced with a methionine (SEQ ID NO: 19 or 219). The sequence for taUBP8 (SEQ ID NO: 19 or 219) comprises C141A and C402A mutations. In some embodiments, the modified taUBP8 comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19,

20, 21, 22, 23, 24, 25, 26, or 27 of the following substitutions: T47C, M48C, S51C, S51I, E64Q, S86C, T90C, Wl 11C, Tl 12C, SI 13C, SI 13A, Al 14C, Rl 16C, Y132A, Y132C, V134A, V134T, V134N, V134Q, V134H, Q135C, Q135A, Q135S, Q135N, Q135A, Q135D, Q135E, Q135H, Q135T, Q135Y, Q135M, Q135L, F136C, E137C, E137Q, E137D, E137A, Y178A, Y178C, V179C, F180A, F180C, L207C, N232A, N232Q, N232S, N232D, N232E, N232H, N232T, N232L, N232C, S259A, S259N, S259Q, S259H, S259C, E262A, A297N, A297K, K301M, T309S, T309D, F351E, and F351G.

In various embodiments, a biosensor comprises a modified gkUBPlO. In non-limiting examples, the modified gkUBPlO may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: T143X, M144X, S147X, E160X, S182X, T186X, W207X, T208X, S209X, A210X, R212X, Y228X, V230X, Q231X, Y232X, E233X, Y274X, V275X, F276X, L303X, N328X, S355X, E358X, K393X, K397X, D405X, and E446X, where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in gkUBPlO with the signal peptide replaced with a methionine (SEQ ID NO: 20). In some embodiments, the modified gkUBP 10 comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,

21, 22, 23, 24, 25, 26, or 27 of the following substitutions: T143C, M144C, S147C, S147I, Attorney Docket No. 35327-522001 WO

E160Q, S182C, T186C, W207C, T208C, S209C, S209A, A210C, R212C, Y228A, Y228C, V230A, V230T, V230N, V230Q, V230H, Q231C, Q231A, Q231S, Q231N, Q231A, Q231D, Q231E, Q231H, Q231T, Q231Y, Q231M, Q231L, Y232C, E233C, E233Q, E233D, E233A, Y274A, Y274C, V275C, F276A, F276C, L303C, N328A, N328Q, N328S, N328D, N328E, N328H, N328T, N328L, N328C, S355A, S355N, S355Q, S355H, S355C, E358A, K393N, K397M, D405S, and E446G.

In various embodiments, a biosensor comprises a modified psUBPl 1. In non-limiting examples, the modified psUBPl 1 may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: T140X, M141X, S144X, E157X, S179X, T183X, W204X, T205X, S206X, A207X, R209X, Y225X, V227X, Q228X, Y229X, E230X, Y244X, V245X, F246X, L300X, N325X, S352X, E355X, K390X, K394X, A402X, and E443X, where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in psUBPl 1 with the signal peptide replaced with a methionine (SEQ ID NO: 21). In some embodiments, the modified psUBPl 1 comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, or 27 of the following substitutions: T140C, M141C, S144C, S144I, E157Q, S179C, T183C, W204C, T205C, S206C, S206A, A207C, R209C, Y225A, Y225C, V227A, V227T, V227N, V227Q, V227H, Q228C, Q228A, Q228S, Q228N, Q228A, Q228D, Q228E, Q228H, Q228T, Q228Y, Q228M, Q228L, Y229C, E230C, E230Q, E230D, E230A, Y244A, Y244C, V245C, F246A, F246C, L300C, N325A, N325Q, N325S, N325D, N325E, N325H, N325T, N325L, N325C, S352A, S352N, S352Q, S352H, S352C, E355A, K390N, K394M, A402S, A402D, and E443G.

In various embodiments, a biosensor comprises a modified teUBP12. In non-limiting examples, the modified teUBP12 may comprise one or more, or any combination of the following substitutions compared to its naturally occurring counterpart: T122X, M123X, S126X, E139X, S161X, T165X, W186X, T187X, S188X, A189X, R191X, Y207X, V209X, Q210X, Y211X, E212X, Y253X, V254X, F255X, L282X, N309X, S336X, E339X, A374X, K378X, N386X, and E428X, where X is any amino acid, an amino acid that results in a conservative substitution, or a cysteine, and where each position is counted in teUBP12 with the signal peptide replaced with a methionine (SEQ ID NO: 22). The sequence for teUBP12 (SEQ ID NO: 22 or 222) comprises C185A, C216A, and C481A mutations. In some embodiments, the modified teUBP 12 comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, or 27 of the following substitutions: T122C, Attorney Docket No. 35327-522001 WO

M123C, S126C, S126I, E139Q, S161C, T165C, W186C, T187C, S188C, S188A, A189C, R191C, Y207A, Y207C, V209A, V209T, V209N, V209Q, V209H, Q210C, Q210A, Q210S, Q210N, Q210A, Q210D, Q210E, Q210H, Q210T, Q210Y, Q210M, Q210L, Y211C, E212C, E212Q, E212D, E212A, Y253A, Y253C, V254C, F255A, F255C, L282C, N309A, N309Q, N309S, N309D, N309E, N309H, N309T, N309L, N309C, S336A, S336N, S336Q, S336H, S336C, E339A, A374N, A374K, K378M, N386S, N386D, and E428G.

In various embodiments, the disassociation constant of the mutant urea-binding polypeptide differs by at least about 1 μΜ, 5 μΜ, 10 μΜ, 20 μΜ, 25 μΜ, 30 μΜ, 35 μΜ, 40 μΜ, 45 μΜ, 50 μΜ, 75 μΜ, 100 μΜ, 200 μΜ, 300 μΜ, 400 μΜ, 500 μΜ, 600 μΜ, 700 μΜ, 800 μΜ, 900 μΜ, 1 mM, 2 mM, 3 mM, 4 mM, 5 mM, 6 mM, 7 mM, 8 mM, 9 mM, 10 mM, 20 mM, 30 mM, 40 mM, 50 mM, 60 mM, 70 mM, 80 mM, 90 mM, 100 mM, 110 mM, 120 mM, 130 mM, 140 mM, 150 mM, 160 mM, 170 mM, 180 mM, 190 mM, or 200 mM

(increase or decrease) compared to its naturally occurring counterpart.

The biosensors and ligand-binding proteins provided herein are robust and useful at a wide range of physical conditions, e.g., pressure, temperature, salinity, osmolality, and pH conditions. For example, biosensors and ligand-binding proteins provided herein may survive substantial periods of time after being dried or exposed to high temperatures. In some embodiments, the biosensor maintains at least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or more of its signal transduction activity after exposure to a temperature of about 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, or 125, or 40-125°C for about 1, 2, 3, 4, 5, 6, 15, 30, 60, 120, 180, 240, or 360 minutes. In certain embodiments, the biosensor maintains at least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or more of its signal transduction activity after 1, 2, 3, 4, or 5 freeze-thaw cycles in an aqueous solution. In various embodiments, the biosensor maintains at least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or more of its signal transduction activity after storage at a temperature of between 20-37°C for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 18, 24, or 1-24 months in dry form. In some embodiments, the optimal functional temperature of the biosensor is between 41 and 122°C, between 20 and 40°C, or less than about 10°C (e.g., between -20 and +10 °C). Devices, compositions, and biosensors provided herein may be stored, e.g., with or without protection from exposure to light. In some embodiments, the devices, compositions, and biosensors are stored in the dark, e.g., with protection from light. Attorney Docket No. 35327-522001 WO

Reporter Group Attachment

Aspects of the present subject matter provide a biosensor that comprises a one or more reporter groups attached to a ligand-binding protein, wherein binding of a ligand to a ligand-binding domain of the ligand-binding protein causes a change in signaling by the reporter group. In various embodiments, the reporter group is attached to an endosteric site, an allosteric site, or a peristeric site of the ligand-binding protein. In embodiments, the reporter group is covalently or noncovalently attached to the ligand-binding protein.

As used herein, "signaling" refers to the emission of energy (which may be referred to as a "signal") by one or more reporter groups. In various implementations, the signal comprises electromagnetic radiation such as a light. In some embodiments, the signal is detected as a complete emission spectrum (or spectrums) or a portion (or portions) thereof. For example, a signal may comprise emitted light at a particular wavelength or wavelengths, or range(s) of wavelengths. In some embodiments, a change in signaling comprises a spectral change (e.g., a spectral shift and/or change in intensity). In some embodiments, a change in signaling comprises a dichromatic shift or a monochromatic fluorescence intensity change.

For convenience and depending on context, a reporter group may be referred to by a name of an unattached form of the reporter group regardless of whether the reporter group is attached to a ligand-binding protein. For example, a compound known as "Compound A" when in an unconjugated form may be referred to herein as "Compound A" when in a form that is attached to a ligand-binding protein. In a specific example, the term "Acrylodan" is used to refer to unreacted/unconjugated Acrylodan, as well as Acrylodan that is conjugated to a ligand-binding protein.

In certain embodiments, a biosensor comprises a reporter group that is conjugated to a ligand-binding protein, and the reporter group is conjugated to an amino acid of the protein that is at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 angstroms (A) from the ligand when the ligand is bound to the protein. In embodiments, the reporter group is conjugated to an amino acid of the protein that is about 0.1 A to about 100 A, about 0.1 A to about 5 A, about 5 A to about 10 A, about 10 A to about 20 A, about 20 A to about 50 A, about 50 A to about 75 A, or about 75 A to about 100 A from the ligand when the ligand is bound to the protein. In some embodiments, the reporter group is conjugated to an amino acid of the protein that is within an a-helix or a β-strand. In some embodiments, the reporter group is conjugated to an amino Attorney Docket No. 35327-522001 WO acid that is not within an a-helix or a β-strand, but is within about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acids of an amino acid of the protein's amino acid sequence that is within an a-helix or a β-strand. In some embodiments, the reporter group is conjugated to an amino acid that is in an inter-domain hinge amino acid region between two domains of a protein. In some embodiments, the reporter group is conjugated to an amino acid that is between (i) a-helix and a β-strand; (ii) two a-helixes; or (iii) two β-strands of a protein. In some embodiments, the reporter group is conjugated to an amino acid (e.g., a cysteine such as a cysteine added by substitution compared to a naturally corresponding polypeptide) between positions 1-25, 25- 50, 50-75, 75-100, 100-125, 125-150, 150-175, 175-200, 200-225, 225-250, 250-275, 275- 350, 275-300, 275-325, 300-325, 300-350, 300-400, or 350-400 (inclusive) of a polypeptide (e.g., not including N-terminal fusion proteins compared to the polypeptide's naturally occurring counterpart).

Periplasmic binding proteins are characterized by two lobes connected by a hinge region; ligand bind at a location at the interface between the two domains. Such proteins or engineered versions thereof (as described herein) can adopt two different conformations: a ligand-free open form and a ligand-bound closed form, which interconvert through a relatively large bending motion around the hinge (Fig 1A; Dwyer et al., 2004, Current Opinion in Structural Biology 12:495-504).

The remarkable adaptability of this superfamily of ligand-binding proteins is likely to have arisen from positioning the location of binding of the ligand at the interface between the lobes and from the large ligand-mediated conformational change. In this arrangement, ligands are placed within an environment that resembles a protein interior, but the residues forming the contact points or contact sites with the ligand are positioned at the surface of the lobes.

Direct signaling relationships between proteins and reporter groups are readily designed by replacing a residue known to form a ligand contact with a cysteine to which the fluorophore is attached ("endosteric" attachment site). Other, indirect signaling relationships can be established in two ways. The first relies on visual inspection of the ligand complex structure, and identifying residues that are located in the vicinity of the binding site, but do not interact directly with the ligand, and that are likely to be involved in conformational changes. Typically, such "peristeric" sites are located adjacent to the residues that form direct contacts with the bound ligand. In the case of the bPBPs, such residues are located at the perimeter of the inter-domain cleft that forms the ligand binding site location. The environment of these peristeric sites changes significantly upon formation of the closed state. Attorney Docket No. 35327-522001 WO

These are examples of positions which are proximal to the ligand-binding pocket/domain. The second, most general, approach identifies sites in the protein structure that are located anywhere in the protein, including locations at some distance away from the ligand-binding site (i.e., distal to the ligand-binding pocket/domain), and undergo a local conformational change in concert with ligand binding. If the structures of both the open and closed states are known, then such "allosteric" sites can be identified using a computational method that analyzes the conformational changes that accompany ligand binding (Marvin et al., Proc. Natl. Acad. Sci. USA 94:4366-4371, 1997). Alternatively, once allosteric sites have been identified in one bPBP, modeling and structural homology arguments can be invoked to identify such sites in other bPBPs in which only one state has been characterized (Marvin & Hellinga, J. Am. Chem. Soc. 120:7-11, 1998). This generalized conformational analysis also may identify peristeric and endosteric sites, which were identified and classified by visual inspection.

In non-limiting implementations, the reporter group is attached to the ligand-binding protein via a biotin-avidin interaction. The reporter group may be, e.g., conjugated to biotin and the ligand-binding protein is conjugated to avidin. In an example, the avidin is bound to four biotin molecules wherein each biotin molecule is individually conjugated to a reporter group. Alternatively, the reporter group is conjugated to avidin and the ligand-binding protein is conjugated to biotin. For example, the avidin is bound to four biotin molecules, wherein each biotin molecule is individually conjugated to a ligand-binding protein.

As used herein, "conjugated" means covalently attached. One compound may be directly conjugated to another compound, or indirectly conjugated, e.g., via a linker.

In some embodiments, the reporter group is directly attached to the ligand-binding protein. In various embodiments, the reporter group is attached to an amino acid of the ligand-binding protein that is at least about 2, 4, 6, 8, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 angstroms (A) from the ligand when the ligand is bound to the ligand-binding protein. In certain embodiments, the reporter group is conjugated to an amino acid having a position within positions 1-25, 25-50, 50-75, 75-100, 100-125, 125-150, 150-175, 175-200, 200-225, 225-250, 250-275, or 275-300 of the ligand-binding protein, wherein position 1 is the N-terminal amino acid of the ligand- binding protein. In non-limiting examples, the reporter group is conjugated to an amino acid of the ligand-binding protein that is (a) within an a-helix or a β-strand of the ligand-binding protein; (b) not within an a-helix; (c) not within a β-strand; (d) within about 5 or 10 amino Attorney Docket No. 35327-522001 WO acids of an amino acid that is within an a-helix or β-strand; (e) within a stretch of consecutive amino acids that links two domains of the ligand-binding protein; (f) within a stretch of consecutive amino acids that links an a-helix and a β-strand; (g) within a stretch of consecutive amino acids that links two a-helices; or (h) within a stretch of consecutive amino acids that links two β-strands. In some embodiments, the reporter group is directly attached to the N-terminus or the C-terminus of the ligand-binding protein.

The reporter group may be conjugated to the ligand-binding protein a variety of linkers or bonds, including (but not limited to) a disulfide bond, an ester bond, a thioester bond, an amide bond, or a bond that has been formed by a click reaction. In some embodiments, the click reaction is a reaction between (a) an azide and an alkyne; (b) an azide and an alkyne in the presence of Cu(I); (c) an azide and a strained cyclooctyne; (d) an azide and a dibenzylcyclooctyne, a difiuorooctyne, or a biarylazacyclooctynone; (e) a diaryl- strained-cyclooctyne and a 1,3-nitrone; (f) an azide, a tetrazine, or a tetrazole and a strained alkene; (g) an azide, a tetrazine, or a tretrazole and a oxanorbornadiene, a cyclooctene, or a trans-cycloalkene; (h) a tetrazole and an alkene; or (i) a tetrazole with an amino or styryl group that is activated by ultraviolet light and an alkene. These exemplary click chemistry reactions have high specificity, efficient kinetics, and occur in vivo under physiological conditions. See, e.g., Baskin et al., 2007, Proc. Natl. Acad. Sci. USA, 104:16793; Oneto et al., 2014, Acta biomaterilia; Neves et al., 2013, Bioconjugate chemistry, 24:934; Koo et al., 2012, Angewandte Chemie, 51 :11836; Rossin et al., 2010, Angewandte Chemie, 49:3375, and U.S. Patent Application Publication No. 20160220686, published August 4, 2016, the entire content of each of which is incorporated herein by reference. For a review of a wide variety of click chemistry reactions and their methodologies, see e.g., Nwe K and Brechbiel M W, 2009, Cancer Biotherapy and Radiopharmaceuticals, 24(3): 289-302; Kolb H C et al., 2001, Angew. Chem. Int. Ed., 40: 2004-2021. The entire contents of each of the foregoing references are incorporated herein by reference.

As used herein, the term "linker" refers to a molecule or sequence (such as an amino acid sequence), that attaches, as in a bridge, one molecule or sequence to another molecule or sequence. "Linked" means attached or bound by covalent bonds, or non-covalent bonds, or other bonds, such as van der Waals forces. In some embodiments, a linker comprises a chemical structure that has resulted from a reaction used to attach one molecule to another.

In various implementations of the present subject matter, the reporter group is conjugated to a cysteine of the ligand-binding protein. The cysteine may be present in the Attorney Docket No. 35327-522001 WO amino acid sequence of a natural counterpart or version of the ligand-binding protein or added to the ligand-binding protein by a substitution mutation in a coding sequence or by altering the sequence synthetically using known chemical means. In some embodiments, the cysteine is at the N-terminus or the C-terminus of the ligand-binding protein. In some embodiments, the cysteine is no more than about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 40, 50, 60, 70, 80, 90, 100, 5-15, 5-20, 5-25, 5-100, 10-15, 10-20, 10-25, 10-50, 10-100, 25-50, 25-75, or 25-100 amino acids from the N- terminus or the C-terminus of the ligand-binding protein. In some embodiments, the cysteine is at least about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 40, 50, 60, 70, 80, 90, 100, 5-15, 5-20, 5-25, 5-100, 10-15, 10-20, 10-25, 10- 50, 10-100, 25-50, 25-75, or 25-100 amino acids from the N-terminus or the C-terminus of the ligand-binding protein.

Non-limiting examples relate to the conjugation of a reporter group to a primary amine of the ligand-binding protein. In certain embodiments, the primary amine is present in a lysine of the ligand-binding protein. The lysine may be present in the amino acid sequence of a natural counterpart or version of the ligand-binding protein or added to the ligand- binding protein by a substitution mutation in a coding sequence or by altering the sequence synthetically using known chemical means. In some embodiments, the lysine is at the N- terminus or the C-terminus of the ligand-binding protein. In some embodiments, the lysine is no more than about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 40, 50, 60, 70, 80, 90, 100, 5-15, 5-20, 5-25, 5-100, 10-15, 10-20, 10-25, 10-50, 10-100, 25-50, 25-75, or 25-100 amino acids from the N-terminus or the C-terminus of the ligand-binding protein. In some embodiments, the lysine is at least about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 40, 50, 60, 70, 80, 90, 100, 5-15, 5-20, 5-25, 5-100, 10-15, 10-20, 10-25, 10-50, 10-100, 25-50, 25-75, or 25- 100 amino acids from the N-terminus or the C-terminus of the ligand-binding protein.

Aspects of the present subject matter provide a biosensor in which the reporter group is attached to the ligand-binding protein via a linker. In some embodiments, the linker comprises an organic compound that is less than about 30, 20, 15, or 10 A long. Non- limiting examples of linkers include O, S, NH, PH, and alkyl linkers.

"Alkyl," as used herein, refers to the radical of saturated or unsaturated aliphatic groups, including straight-chain alkyl, alkenyl, or alkynyl groups, branched-chain alkyl, alkenyl, or alkynyl groups, cycloalkyl, cycloalkenyl, or cycloalkynyl (alicyclic) groups, alkyl Attorney Docket No. 35327-522001 WO substituted cycloalkyl, cycloalkenyl, or cycloalkynyl groups, and cycloalkyl substituted alkyl, alkenyl, or alkynyl groups. Unless otherwise indicated, a straight chain or branched chain alkyl has 30 or fewer carbon atoms in its backbone (e.g., Q-C30 for straight chain, C3-C30 for branched chain), more preferably 20 or fewer carbon atoms, more preferably 12 or fewer carbon atoms, and most preferably 8 or fewer carbon atoms. Likewise, preferred cycloalkyls have from 3-10 carbon atoms in their ring structure, and more preferably have 5, 6 or 7 carbons in the ring structure. The ranges provided above are inclusive of all values between the minimum value and the maximum value. The term "alkyl" includes both "unsubstituted alkyls" and "substituted alkyls," the latter of which refers to alkyl moieties having one or more substituents replacing a hydrogen on one or more carbons of the hydrocarbon backbone. Such substituents include, but are not limited to, halogen, hydroxyl, carbonyl (such as a carboxyl, alkoxycarbonyl, formyl, or an acyl), thiocarbonyl (such as a thioester, a thioacetate, or a thioformate), alkoxyl, phosphoryl, phosphate, phosphonate, a phosphinate, amino, amido, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclyl, aralkyl, or an aromatic or heteroaromatic moiety. Unless the number of carbons is otherwise specified, "lower alkyl" as used herein means an alkyl group, as defined above, but having from one to ten carbons, more preferably from one to six carbon atoms in its backbone structure. Likewise, "lower alkenyl" and "lower alkynyl" have similar chain lengths. Preferred alkyl groups are lower alkyls. The alkyl groups may also contain one or more heteroatoms within the carbon backbone. Preferably the heteroatoms incorporated into the carbon backbone are oxygen, nitrogen, sulfur, and combinations thereof. In certain embodiments, the alkyl group contains between one and four heteroatoms.

In some embodiments, the linker comprises a bond formed by a chemical reaction involving a reactive group such as a maleimide group. Alternatively or in addition, the linker comprises a stretch of amino acids. In a non-limiting example, the linker comprises a polyglycine linker. In embodiments, the polyglycine linker comprises 2, 3, 4, 5, or more glycines. Optionally, the polyglycine linker further comprises a serine.

In various implementations, the reporter group is attached to a linker via a covalent bond and the linker is attached to a ligand-binding protein via a covalent bond. In

embodiments, the covalent bond between the linker and the reporter group and/or the covalent bond between the linker and the ligand-binding protein is a disulfide bond, an ester bond, a thioester bond, an amide bond, a carbamate bond, or a bond that has been formed by Attorney Docket No. 35327-522001 WO a click reaction. Non-limiting examples of click reactions include reactions between an azide and an alkyne; an azide and an alkyne in the presence of Cu(I); an azide and a strained cyclooctyne; an azide and a dibenzylcyclooctyne, a difluorooctyne, or a

biarylazacyclooctynone; a diaryl-strained-cyclooctyne and a 1,3-nitrone; an azide, a tetrazine, or a tetrazole and a strained alkene; an azide, a tetrazine, or a tretrazole and a

oxanorbornadiene, a cyclooctene, or a trans-cycloalkene; a tetrazole and an alkene; or a tetrazole with an amino or styryl group that is activated by ultraviolet light and an alkene.

Reporter Groups

Various types of reporter groups may be used in embodiments of the present subject matter. For example, the reporter group may comprise a fluorophore that produces a fluorescent signal. Biosensors comprising a fluorophore may be referred to herein as fluorescently responsive sensors (FRSs).

Preferably, the binding of ligand to an FRS results in a change in ratiometric AR in the signal from a reporter group. A ratiometric signal (i- _1;2 ) is defined as the quotient of two intensities, I _\\ and I%2, measured at two independent wavelengths, λ] and λ ₂ and may be calculat to the following equation:

In some embodiments, intensities are, e.g., integrated, filtered, assessed, detected, or evaluated over a range of wavelengths. In some embodiments, intensities are integrated over a range of wavelengths in a recorded emission spectrum. In some embodiments, a range of wavelengths is selected using a filter. In some embodiments, λ] is the intensity over a 1 nm to 60 nm interval centered between 400 and 1000 nm, and λ ₂ is the intensity over a 1 nm to 60 nm interval centered between 400 nm and 1000 nm. In some embodiments, intensities are integrated, filtered, assessed, detected, or evaluated over a 1 nm, 2 nm, lOnm, 15nm, 20nm, 25nm, 30nm, 35nm, 40nm, 45nm, 50nm, 55 nm, 60 nm, 75 nm, 100 nm, 10-40 nm, 10-50 nm, 20-50 nm, or 10-100 nm regions, centered between 400-1000 nm, e.g. between 420 nm and 520 nm for λ _ΐ5 and 400-lOOOnm, e.g. between 500 nm to 600 nm for λ ₂ . In some embodiments, intensities are recorded through a bandpass filter. A non-limiting example of a bandpass filter is a 10 nm, 15-nm, 20 nm, 25 nm, 30 nm, 35 nm, 40 nm, 45 nm, 50 nm, 75 nm, 100 nm, 10-40 nm, 10-50 nm, 20-50 nm, or 10-100 nm bandpass filter, centered between 400-1000 nm, e.g. at 452 nm ϋοτλι and at 400-lOOOnm, e.g. at 528 nm (λ ₂ ). Attorney Docket No. 35327-522001 WO

Aspects of the present subject matter provide FRSs whose emission spectra change (e.g., the shape of the emission spectra change) in response to ligand binding. In various embodiments, the ratio of intensities at two chosen wavelengths of an FRS's emission spectrum changes upon ligand binding. In some embodiments, the emission spectral shape and/or intensity of the fluorophore changes when the position of atoms within the fluorophore changes with respect to each other (e.g., due to the rotation of bound atoms with respect to each other or a change in the angle of a bond). In non-limiting examples, the emission spectral shape and/or intensity of the fluorophore changes when (i) one portion of the fluorophore rotates around a bond axis compared to another portion of the fluorophore and/or (ii) when the angle of a bond between two atoms of the fluorophore changes. In a non- limiting example, the fluorophore is a prodan-derived fluorophore (e.g., Acrylodan or Badan) and binding of ligand alters the orientation of a dimethylamino group, a naphthalene ring, and/or a carbonyl with respect to the ligand-binding protein and/or each other. In another non-limiting example, the fluorophore is Alexa532. In a non-limiting example, the degree of polarization of a dipole on the fluorophore changes in response to ligand binding. In various embodiments, the emission spectral shape and/or intensity of the fluorophore changes when an atom electrostatically interacts with the fluorophore. For example, the emission spectral shape and/or intensity of the fluorophore changes when the source of a positive or negative charge changes its distance with respect to the fluorophore within about 1, 2, 3, 4, 5, or 10 A of the fluorophore. In some embodiments, the fluorophore exhibits hypsochromicity or bathochromicity upon ligand binding to the ligand-binding domain of the ligand-binding protein. In certain embodiments, the fluorophore has an emission spectrum comprising radiation with a wavelength (e.g., a peak emission wavelenght) of about 400 nm, 410 nm, 420 nm, 430 nm, 440 nm, 450 nm, 460 nm, 470 nm, 480 nm, 490 nm, 500 nm, 510 nm, 520 nm, 530 nm, 540 nm, 550 nm, 560 nm, 570 nm, 580 nm, 590 nm, 600 nm, 610 nm, 620 nm, 630 nm, 640 nm, 650 nm, 660 nm, 670 nm, 680 nm, 690 nm, 700 nm, 710 nm, 720 nm, 730 nm, 740 nm, 750 nm, 760 nm, 770 nm, 780 nm, 790 nm, 800 nm, 850 nm, 900 nm, 950 nm, or 1000 nm, or about 400 nm to about 450 nm, about 450 nm to about 500 nm, about 500 nm to about 550 nm, about 550 nm to about 600 nm, about 600 nm to about 650nm, about 650 to about 700 nm, about 700 nm to about 750 nm, about 750 nm to about 800 nm, or about 800 nm to about 1000 nm.

In some embodiments, the signal comprises the emission intensity of the fluorophore recorded at a single wavelength or range of wavelengths. The change in signal may be a shift Attorney Docket No. 35327-522001 WO in the single wavelength or range of wavelengths. In some embodiments, the shift in the wavelength is at least about 1 nm, at least about 2 nm, at least about 3 nm, at least about 4 nm, at least about 5 nm, at least about 6 nm, at least about 7 nm, at least about 8 nm, at least about 9 nm, at least about 10 nm, at least about 11 nm, at least about 12 nm, at least about 13 nm, at least about 14 nm, at least about 15 nm, at least about 16 nm, at least about 17 nm, at least about 18 nm, at least about 19 nm, at least about 20 nm, at least about 25 nm, at least about 30 nm, at least about 35 nm, at least about 40 nm, at least about 45 nm, at least about 50 nm, at least about 55 nm, at least about 60 nm, at least about 65 nm, at least about 70 nm, at least about 75 nm, at least about 80 nm, at least about 85 nm, at least about 90 nm, at least about 95 nm, at least about 100 nm, at least about 105 nm, at least about 110 nm, at least about 115 nm, at least about 120 nm, at least about 125 nm, or at least about 130 nm. In some embodiments, the shift in the wavelength is about 1 nm to about 20 nm, about 2 nm to about 20 nm, about 3 nm to about 20 nm, about 4 nm to about 20 nm, about 5 nm to about 20 nm, about 1 nm to about 19 nm, about 1 nm to about 18 nm, about 1 nm to about 17 nm, 1 nm to about 16 nm, about 1 nm to about 15 nm, about 1 nm to about 14 nm, about 1 nm to about 13 nm, about 1 nm to about 12 nm, about 1 nm to about 11 nm, or about 1 nm to about 10 nm. In some embodiments, the shift in the wavelength is about 1 nm to about 20 nm. In some embodiments, the shift in the wavelength is about 1 nm to about 130 nm.

In certain embodiments, the signal comprises the ratio or quotient of the emission intensities recorded at two distinct wavelengths or ranges of wavelengths, i.e., a ratiometric signal. For example, as shown in FIG. 1 A-D, ligand binding may be determined by measuring the ratio of blue to green emission intensities. The change in signal may be decreased emission intensity at one wavelength, and no change in emission intensity at the other wavelength. The change in signal may be increased emission intensity at one wavelength, and no change in emission intensity at the other wavelength. The change in signal may be increased emission intensity at one wavelength, and increased emission intensity at the other wavelength. The change in signal may be decreased emission intensity at one wavelength, and decreased emission intensity at the other wavelength. The change in signal may be increased emission intensity at one wavelength, and decreased emission intensity at the other wavelength. In some embodiments, the change in ratio of the emission intensities recorded at two distinct wavelengths or ranges of wavelengths may be at least about 1.1-fold, at least about 1.2-fold, at least about 1.4-fold, at least about 1.6-fold, at least about 1.8-fold, at least about 2.0-fold, at least about 2.5-fold, at least about 3-fold, at least Attorney Docket No. 35327-522001 WO about 3.5-fold, at least about 4-fold, at least about 4.5-fold, at least about 5-fold, at least about 5.5-fold, at least about 6-fold, at least about 6.5-fold, at least about 7-fold, at least about 7.5- fold, at least about 8-fold, at least about 8.5-fold, at least about 9-fold, at least about 9.5-fold, at least about 10-fold, at least about 12-fold, at least about 14-fold, at least about 16-fold, at least about 18-fold, at least about 20-fold, at least about 25-fold, at least about 30-fold, at least about 35-fold, at least about 40-fold, at least about 45-fold, at least about 50-fold, at least about 55-fold, at least about 60-fold, at least about 65-fold, at least about 70-fold, at least about 75-fold, at least about 80-fold, at least about 85-fold, at least about 90-fold, at least about 95-fold, or at least about 100-fold. In some embodiments, the change in ratio of the emission intensities recorded at two distinct wavelengths or ranges of wavelengths may be a decrease of at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or of 5-25%, 25- 50%, 25-75%, 50-75%, 50-90%, or 75-99% or the reciprocal thereof.

The change in signal may be a change in the ratio of the two distinct wavelengths or ranges of wavelengths. The change in signal may be a shift in the two distinct wavelengths or ranges of wavelengths. In some embodiments, one wavelength shifts. In some embodiments, both wavelengths shift. In some embodiments, the shift in the wavelength is at least about 1 nm, at least about 2 nm, at least about 3 nm, at least about 4 nm, at least about 5 nm, at least about 6 nm, at least about 7 nm, at least about 8 nm, at least about 9 nm, at least about 10 nm, at least about 11 nm, at least about 12 nm, at least about 13 nm, at least about 14 nm, at least about 15 nm, at least about 16 nm, at least about 17 nm, at least about 18 nm, at least about 19 nm, at least about 20 nm, at least about 25 nm, at least about 30 nm, at least about 35 nm, at least about 40 nm, at least about 45 nm, at least about 50 nm, at least about 55 nm, at least about 60 nm, at least about 65 nm, at least about 70 nm, at least about 75 nm, at least about 80 nm, at least about 85 nm, at least about 90 nm, at least about 95 nm, at least about 100 nm, at least about 105 nm, at least about 110 nm, at least about 115 nm, at least about 120 nm, at least about 125 nm, or at least about 130 nm. In some embodiments, the shift in the wavelength is about 1 nm to about 20 nm, about 2 nm to about 20 nm, about 3 nm to about 20 nm, about 4 nm to about 20 nm, about 5 nm to about 20 nm, about 1 nm to about 19 nm, about 1 nm to about 18 nm, about 1 nm to about 17 nm, 1 nm to about 16 nm, about 1 nm to about 15 nm, about 1 nm to about 14 nm, about 1 nm to about 13 nm, about 1 nm to about 12 nm, about 1 nm to about 11 nm, or about 1 nm to about 10 nm. In some embodiments, the Attorney Docket No. 35327-522001 WO shift in the wavelength is about 1 nm to about 20 nm. In some embodiments, the shift in the wavelength is about 1 nm to about 130 nm.

A fluorophore may comprise, e.g., a fluorescent protein or an organic compound having a molecular weight less than about 2000 Daltons (Da). Non-limiting examples of commercially available fluorophores include such as 5-iodoacetamidofluorescein (5-IAF) or 6-iodoacetamidofluorescein (6-IAF), rhodamine, Oregon Green, eosin, Texas Red, indocarbocyanine, oxacarbocyanine, thiacarbocyanine, merocyanine, Badan, Acrylodan, IAEDANS, comprising 3-cyano-7-hydroxycoumarin, 7-hydroxycoumarin-3-carboxylic acid, 6,8-difluoro-7-hydroxy- 4-methylcoumarin, or 7-amino-4-methylcoumarin, pyridyloxazole, nitrobenzoxadiazole, benzoxadiazole, DRAQ5, DRAQ7, or CyTRAK Orange, cascade blue, Nile red, Nile blue, cresyl violet, oxazine 170, profiavin, acridine orange, acridine yellow, auramine, crystal violet, malachite green, porphin, phthalocyanine, bilirubin, pyrene, Ν,Ν'- dimethyl-N-(iodoacetyl)-N'-(7-nitrobenz-2-ox- a-l,3-diazol-4-yl)ethylenediamide (NBD), N- ((2-(iodoacetoxy)ethyl)-N-methy- l)amino-7-nitrobenz-2-oxa-l,3-diazole (NBDE), JPW4039, JPW4042, JPW4045, Pacific Blue, CPM, N,N'-Dimethyl-N-(Iodoacetyl)-N'-(7-Nitrobenz-2- Oxa-1 ,3-Diazol-4-yl)Ethylenediamine (IANBD), 7-diethylamino-3-(4'-maleimidylphenyl)-4- methylcoumarin (CPM), BODIPY 499, BODIPY 507/545, BODIPY 499/508, Alexa 432, Alexa488, Alexa532, Alexa546, Cy5, or l-(2-maleimidylethyl)-4-(5-(4- methoxyphenyl)oxazol-2- yl)pyridinium methanesulfonate (PyMPO maleimide) (PyMPO). In various embodiments, the reporter group was thiol-reactive prior to being conjugated to a polypeptide disclosed herein. In embodiments, the reporter group is linked to a polypeptide disclosed herein via a disulfide bond. Additional non-limiting examples of commercially available fluorophores include fluorescent proteins such as Blue Fluorescent Protein (BFP), TagBFP, mTagBFP2, Azurite, Enhanced Blue Florescent Protein 2 (EBFP2), mKalamal, Sirius, Sapphire, T-Sapphire, Cyan Fluorescent Protein (CFP); Enhanced Cyan Fluorescent Protein (ECFP), Cerulean, SCFP3A, mTurquoise, mTurquoise2, monomeric Midoriishi- Cyan, TagCFP, mTFPl, AmCyanl, Green Fluorescent Protein (GFP), Enhanced Green Fluorescent Protein (EGFP), Emerald, Superfolder GFP, AcGFPl, ZsGreenl, Monomeric Azami Green, TagGFP2, mUKG, mWasabi, Clover, mNeonGreen, Yellow Fluorescent Protein (YFP), Enhanced Yellow Fluorescent Protein (EYFP), Citrine, Venus, Super Yellow Fluorescent Protein 2 (SYFP2), TagYFP, ZsYellowl, mBanana, Orange Fluorescent Protein (OFP), Monomeric Kusabira-Orange (mKO), ιηΚΟκ, mK02, mOrange, mOrange2, Red Fluorescent Protein (RFP), DsRed-Express, DsRed-Express2, DsRed2, AsRed2, mRaspberry, Attorney Docket No. 35327-522001 WO mCherry, mStrawberry, mTangerine, tdTomato, TagRFP, TagRFP-T, mApple, mRuby, mRuby2, mPlum, HcRed-Tandem, mKate2, mNeptune, HcRedl, E2-Crimson, NirFP, TagRFP657, IFP1.4, or iRFP.

In some embodiments, the fluorophore comprises xanthene, a xanthene derivative, cyanine, a cyanine derivative, squaraine, a squaraine derivative, naphthalene, a naphthalene derivative, coumarin, a coumarin derivative, oxadiazole, an oxadiazole derivative, anthracene, an anthracene derivative, a boradiazaindacine (BODIPY) family fluorophore, pyrene, a pyrene derivative, acridine, an acridine derivative, arylmethine, an arylmethine derivative, tetrapyrrole, or a tetrapyrrole derivative. For example, the fluorophore may comprise a xanthene derivative comprising fluorescein or a fluorescein derivative, rhodamine, Oregon Green, eosin, or Texas Red. Non-limiting examples of fluorescein derivatives include 5-fluorescein, 6-carboxyfluorescein, 3'6-carboxyfluorescein, 5(6)- carboxyfluorescein, 6-hexachlorofluorescein, 6-tetrachlorofluorescein, or isothiocyanate. In some embodiments, the fluorophore comprises a cyanine derivative comprising

indocarbocyanine, oxacarbocyanine, thiacarbocyanine, or merocyanine. In certain embodiments, the fluorophore comprises a squaraine derivative comprising a ring-substituted squaraine. In various embodiments, the fluorophore comprises a naphthalene derivative comprising a dansyl or prodan naphthalene derivative. In a non-limiting example, the fluorophore comprises prodan or a derivative thereof. In certain embodiments, the fluorophore comprises Badan, Acrylodan, or N-(Iodoacetaminoethyl)-l-naphthylamine-5- sulfonic acid (IAEDANS). In some embodiments, the fluorophore comprises a coumarin derivative such as 3-cyano-7-hydroxycoumarin, 7-hydroxycoumarin-3-carboxylic acid, 6,8- difluoro-7-hydroxy- 4-methylcoumarin (DiFMU), or 7-amino-4-methylcoumarin. In various embodiments, the fluorophore comprises an oxadiazole derivative such as pyridyloxazole, nitrobenzoxadiazole, or benzoxadiazole. In certain embodiments, the fluorophore comprises an anthracene derivative comprising an anthraquinone such as DRAQ5, DRAQ7, or CyTRAK Orange. In various embodiments, the fluorophore comprises a pyrene derivative comprising cascade blue. In non-limiting examples the fluorophore comprises an oxazine derivative such as Nile red, Nile blue, cresyl violet, or oxazine 170. In some embodiments, the fluorophore comprises an acridine derivative such as proflavin, acridine orange, or acridine yellow. In certain embodiments, the fluorophore comprises an arylmethine derivative such as auramine, crystal violet, or malachite green. In various embodiments, the Attorney Docket No. 35327-522001 WO fluorophore comprises a tetrapyrrole derivative comprising porphin, phthalocyanine, or bilirubin.

Aspects of the present subject matter relate to the use of fluorophores that may readily be attached to a ligand-binding protein disclosed herein, e.g., at a cysteine residue. For example, a fluorophore may comprise a sulfhydryl group prior to attachment to a ligand- binding protein that is reacted with a moiety of the ligand-binding protein to attach the fluorophore to the ligand-binding protein. In some embodiments, the fluorophore comprised a thiol group prior to attachment to the ligand-binding protein. For example, the fluorophore was thiol reactive prior to attachment to the ligand-binding protein. Non-limiting examples of fluorophores that may readily be attached to ligand-binding proteins using thiol reactions include fluorescein, pyrene, NBD, NBDE, Acrylodan (6-acryloyl 1-2- dimethylaminonaphthalene), Badan (6-bromo-acetyl-2-dimethylamino-naphthalene), JPW4039, JPW4042, or JPW4045.

In certain embodiments, the fluorophore comprises a derivative of a Prodan-based fluorophore such as Acrylodan or Badan. The excitation and emission properties of the Prodan-based fluorophores Acrylodan and Badan can be altered by manipulating the fluorescent ring system, while preserving the dimethylamino donor group, and the twistable carbonyl acceptor (Klymchenko, 2013, Progress in Molecular Biology and Translational Science, 35-58). Replacement of the two-ring naphthalene with a three-ring anthracene (Lu, 2006, J. Org. Chem., 71, 9651-9657), fluorene (Kucherak, 2010, J. Phys. Chem. Lett, 1, 616- 620), pyrene (Niko, 2013, Chem. Eur. J., 19, 9760-9765), or styrene (Benedetti, 2012, J. Am. Chem. Soc, 134, 12418-12421) cores significantly red-shift the excitation and emission properties, and in the case of the latter two, improve brightness through improvements in their excitation peak extinction coefficients. The entire content of each of the references cited above (as well as all other references referred to herein including the contents of nucleic acid and amino acid sequence accession number references) are incorporated herein by reference. Non-limiting examples of prodan analogues include 2-cyano-6- dihexylaminoanthracene and 2-propionyl-6-dihexylaminoanthracene, as well as fluorophores comprising the following structures: Attorne Docket No. 35327-522001 WO

In some embodiments, the fluorophore comprises Alexa532.

In some embodiments, the fluorophore comprises a fluorescent protein. Fluorescent proteins that emit blue, cyan, green, yellow, orange, red, far-red, or near infrared radiation when contacted with excitation radiation are known in the art and commercially available as proteins and via the expression of vectors that encode the fluorescent protein. Non-limiting examples of fluorescent proteins include Blue Fluorescent Protein (BFP), TagBFP, mTagBFP2, Azurite, Enhanced Blue Florescent Protein 2 (EBFP2), mKalamal, Sirius, Sapphire, T-Sapphire, Cyan Fluorescent Protein (CFP); Enhanced Cyan Fluorescent Protein (ECFP), Cerulean, SCFP3A, mTurquoise, mTurquoise2, monomeric Midoriishi-Cyan, TagCFP, mTFPl, AmCyanl, Green Fluorescent Protein (GFP), Enhanced Green Fluorescent Protein (EGFP), Emerald, Superfolder GFP, AcGFPl, ZsGreenl, Monomeric Azami Green, TagGFP2, mUKG, mWasabi, Clover, mNeonGreen, Yellow Fluorescent Protein (YFP), Enhanced Yellow Fluorescent Protein (EYFP), Citrine, Venus, Super Yellow Fluorescent Protein 2 (SYFP2), TagYFP, ZsYellowl, mBanana, Orange Fluorescein Protein (OFP), Monomeric Kusabira-Orange (mKO), ιηΚΟκ, mK02, mOrange, mOrange2, Red Fluorescent Protein (RFP), DsRed-Express, DsRed-Express2, DsRed2, AsRed2, mRaspberry, mCherry, mStrawberry, mTangerine, tdTomato, TagRFP, TagRFP-T, mApple, mRuby, mRuby2, mPlum, HcRed-Tandem, mKate2, mNeptune, HcRedl, E2-Crimson, NirFP, TagRFP657, IFP1.4, or iRFP.

In some embodiments, the fluorophore comprises a quantum dot (Medintz et al., 2005, Nat Mater., 4(6):435-46.) (Sapsford, Berti and Medintz, 2006, Angew Chem IntEd Engl, 45, 4562-89; Resch-Genger et al., 2008, Nat Methods, 5, 763-75). In some embodiments the emission properties of the conjugated protein are enhanced by Attorney Docket No. 35327-522001 WO immobilization on or near metallic nanoparticles (Zeng et al., 2014, Chem Soc Rev, 43, 3426- 52; Shen et al., 2015, Nanoscale, 7, 20132-41).

In various embodiments, the peak emission wavelength and/or the emission intensity of the biosensor change when the ligand binds to the ligand-binding protein. In some embodiments, the biosensor exhibits a dichromatic signaling change when the ligand binds to the ligand-binding protein. In various embodiments, the peak emission wavelength of the biosensor shifts by at least about 5, 10, 15, 20, 30, 40, 50, or by about 5-50 nm when the biosensor binds to ligand. In certain embodiments, the emission intensity of the biosensor increases by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, or 300% when the biosensor binds to ligand. In various embodiments, the signal produced by the reporter group persists for at least 1 nanoseconds (ns), 5 ns, 10 ns, 25 ns, 50 ns, 75 ns, 100 ns, 200 ns, 300 ns, 400 ns, 500 ns, 600 ns, 700 ns, 800 ns, 900 ns, 0.001 milliseconds (ms), 0.01 ms, 0.1 ms, 1 ms, 5 ms, 10 ms, 20 ms, 25 ms, 50 ms, 100 ms, or 500 ms when the ligand binds to the ligand-binding protein.

Ratiometric Sensing with Fluorescence Energy Transfer

The present subject matter provides methods for converting monochromatic responses into dichromatic responses that enable ratiometric sensing. If the fluorescence emission spectrum changes shape in response to analyte binding such that the ratio of emission intensities at two appropriately chosen wavelengths reports on analyte concentration

(dichromatic response), then ratiometric measurements can be used to monitor analyte concentrations. In embodiments, these methods are based on establishing non-geometrically modulated Forster resonance energy transfer (ngmFRET) between a fluorophore (a directly responsive partner), and a second fluorophore that neither interacts directly with the ligand, nor is sensitive to ligand-mediated changes in its environment (an indirectly responsive partner). Biosensors that undergo ngmFRET (or altered ngmFRET) upon ligand binding are also provided herein, as well as compositions and devices comprising such biosensors.

Methods, compounds, and compositions provided herein overcome challenges regarding the design of biosensors that produce a ratiometric signal. For example, a biosensor that exhibits a monochromatic response (which does not produce a ratiometric signal) to ligand binding may be converted into a biosensor that produces a

dichromatic/ratiometric signal. Moreover, the number of fluorophores that may be utilized in ratiometric biosensors is dramatically increased by the present subject matter. For example, Attorney Docket No. 35327-522001 WO fluorophores that typically do not show a dichromatic response to ligand binding (such as fluorescein and derivatives thereof) may be used together with an additional reporter group (such as another fluorophore) to produce a ratiometric signal. Also included are methods, compounds, and compositions relating to biosensors with multiple reporter groups that have improved ratiometric signals compared to other ratiometric biosensors (e.g., ratiometric biosensors having a single reporter group).

Traditional/conventional geometrically-modulated Fluorescence Resonance Energy Transfer (tgmFRET) is a physical phenomenon that was first described over 50 years ago. In tgmFRET, the transfer of excited state energy from a donor fluorophore to an acceptor fluorophore (i.e. energy transfer) is modulated by a ligand-binding event through changes in the distance and/or angle between the donor and acceptor fluorophores. tgmFRET is manifested by opposing changes in the fluorescence emission intensities of the donor and acceptor fluorophores, respectively, in response to ligand binding. For instance, a decrease in distance results in a decrease of the donor fluorescence emission intensity and an increase in the acceptor fluorescence intensity, as energy is transferred from the former to the latter. A ligand-mediated increase in the distance between the partners has the opposite effect (the fluorescence emission intensity of the donor increases, whereas that of the acceptor decreases). In tgmFRET, ligand-mediated modulation of fluorescence intensity arises from global changes in the entire system, and can occur only if both partners are present.

By contrast, in ngmFRET ligand-mediated modulation of fluorescence intensity arises from changes that are localized to the photophysics of the directly responsive fluorophore. Unlike tgmFRET, ligand-mediated changes in fluorescence therefore occur also if only the directly responsive partner is present in isolation by itself. Although the entire ngmFRET system comprising two partners is not required for evincing ligand-mediated changes in fluorescence emission intensity, the response of such a system is qualitatively changed or quantitatively enhanced over the responses of the isolated directly responsive partner (e.g. converting a monochromatic into a dichromatic response, thereby enabling ratiometry). Furthermore, unlike tgmFRET, the pattern of fluorescence intensity changes manifested by ligand binding in ngmFRET systems are not limited to opposing changes only. Instead, in ngmFRET almost all combinations of emission intensity changes are possible: opposing changes in the two partners, both partners increase, both decrease, one partner remains unchanged whereas the other increases or decreases. The majority of these responses evince changes that are unequal in magnitude and/or direction (i.e. increase, decrease), and Attorney Docket No. 35327-522001 WO accordingly are manifested as ligand-mediated changes in the ratio of the two fluorescence emission intensities. This versatility of ngmFRET system response patterns has great utility in the field of fluorescent biosensors.

The ligand-mediated alteration of the photophysics of the directly responsive partner includes changes to its spectral properties such as the shape of the excitation or emission spectra, and the ratio of radiative to non-radiative emission rates. The fluorescence emission intensity of the indirectly responsive partner in isolation does not change in response to ligand binding; its intensity changes only in the presence of a directly responsive partner in the complete ngmFRET system. In the field fluorescence spectroscopy, the term

"quenching" has often been used loosely to refer to a decrease fluorescence emission intensity. However, as used herein, the term "quenching" strictly means a "change in the ratio of radiative to non-radiative emission rates" of a fluorophore.

Aspects of the present subject matter provide biosensors in which ngmFRET occurs between two or more reporter groups (e.g., a donor fluorophore and an acceptor fluorophore) of the biosensor. For example, ngmFRET may change (e.g., increase or decrease) when ligand is bound to the biosensor and a donor fluorophore is contacted with radiation within its excitation wavelength. Effects from tgmFRET and ngmFRET may occur together and be combined into an overall ligand-mediated change in fluorescence emission intensity. In preferred embodiments, less than half or none of the change in overall ligand-mediated change in fluorescence emission intensity is due to tgmFRET. In embodiments, most of the overall ligand-mediated change in fluorescence emission intensity change is not due to a change in the distance between the donor and acceptor fluorophore or as a result of a change in the orientation between the donor and acceptor fluorophore. In non-limiting examples, less than about 25%, 20%, 15%, 10%, 5%, 4%, 3%, 2%, 1%, or 0.5% of the change in overall ligand-mediated change in fluorescence emission intensity is due to tgmFRET. In various embodiments, at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or 99.99% of the ligand-mediated change in fluorescence emission intensity is due to ngmFRET. For example, the change in overall ligand-mediated change in fluorescence emission intensity comprises a spectral change (e.g., in the excitation or emission spectrum) and/or a change in the ratio of the radiative to non-radiative decay rates of one of the fluorophores (by itself and regardless of the presence of any other fluorophore/partner) upon ligand binding. Attorney Docket No. 35327-522001 WO

In some embodiments, ligand binding mediates spectral shifts in the absorption or emission spectrum of the directly responsive partner. In certain embodiments such changes are due at least in part to a switch between different excited states in the ligand-free and ligand-bound biosensor. The two excited states are associated with different transition dipoles. This class of changes is termed "dipole switching" herein.

In embodiments, the reporter groups include a directly responsive partner (which may be a donor fluorophore or an acceptor fluorophore) and an indirectly responsive partner (which may be a donor fluorophore or an acceptor fluorophore). Depending on context, a "directly responsive" partner is a fluorophore that responds to (i) ligand-induced protein conformational changes upon ligand binding to a ligand-binding protein; or (ii) ligand binding to the directly responsive partner itself. In some embodiments, the directly responsive partner comprises a fluorophore(i ^' .e., it is a directly responsive fluorophore). In various embodiments, the directly responsive fluorophore exhibits a monochromatic or dichromatic spectral change, and/or a change in the ratio of radiative to non-radiative emission rates, upon ligand binding. In certain embodiments relating to ligand binding to the directly responsive partner itself, the directly responsive partner may be a fluorophore such as a fluorescent protein or a small molecule fluorescent compound. An "indirectly responsive" partner is a fluorophore for which no change in emission spectra, excitation spectra, or change in the ratio of radiative to non-radiative emission rates is caused by ligand binding in the absence of a directly responsive partner. In some embodiments, the indirectly responsive partner comprises a fluorophore (i.e., it is an indirectly responsive fluorophore). When paired with a directly responsive partner with which the indirectly responsive partner is a ngmFRET donor or acceptor, the emission fluorescence intensity of the indirectly responsive partner changes due to a change in energy flow in the ngmFRET pathway upon ligand binding. See, e.g., FIG. 110.

ngmFRET Biosensors

Provided herein are methods, compositions, biosensors, and devices comprising multiple reporter groups, e.g. a directly responsive fluorophore and an indirectly responsive fluorophore, between which ngmFRET occurs.

Aspects include a method of detecting a urea in a sample, comprising contacting a biosensor with a urea. The biosensor comprises a urea-binding protein, a directly responsive fluorophore and an indirectly responsive fluorophore. The directly responsive and the indirectly responsive fluorophores are located at two distinct sites of the urea-binding-protein. Attorney Docket No. 35327-522001 WO

In some embodiments, the directly responsive fluorophore is a donor fluorophore and the indirectly responsive fluorophore is an acceptor fluorophore. Alternatively, the directly responsive fluorophore is an acceptor fluorophore and the indirectly responsive fluorophore is a donor fluorophore. The method includes contacting the biosensor with radiation comprising a wavelength within the excitation spectrum of the donor fluorophore. When the biosensor is contacted with such radiation, a fluorescence property of the directly responsive fluorophore changes in response to urea binding. This change in fluorescent property is independent of the indirectly responsive fluorophore, and occurs regardless of whether the indirectly responsive fluorophore is absent or present. The fluorescence properties of the indirectly responsive fluorophore do not change in response to urea binding in the absence of the directly responsive fluorophore. When the biosensor is contacted with radiation comprising a wavelength within the excitation spectrum of the donor fluorophore, then (i) ngmFRET occurs between the directly responsive fluorophore and the indirectly responsive fluorophore; (ii) fluorescent light is emitted from the biosensor, and the light emitted from the biosensor comprises a combination of light emitted from the directly responsive fluorophore and light emitted from the indirectly responsive fluorophore; and (iii) the ratio of the fluorescence emission intensity emitted from the biosensor at each of two distinct wavelengths changes in response to urea binding. In various embodiments, the method further comprises measuring fluorescent light that is emitted from the directly responsive fluorophore and the indirectly responsive fluorophore, and calculating a ratiometric signal to detect the urea in the sample.

The ratiometric signal (i- _1;2 ) comprises a quotient of two intensities, I _\\ and I _%2 , measured at two independent wavelengths, λ] and λ ₂ and is calculated according to the following equation:

The two independent wavelengths λ] and λ ₂ may be from a single fluorophore or from a combination of two or more fluorophores (e.g., a pair of fluorophores between which ngmFRET occurs). In some embodiments, λ] falls within the emission spectrum of a directly responsive fluorophore and λ ₂ falls within the emission spectrum of an indirectly responsive fluorophore. In certain embodiments, λ] falls within the emission spectrum of an indirectly responsive fluorophore and λ ₂ falls within the emission spectrum of a directly responsive fluorophore. In various embodiments, λ] falls within the emission spectrum of both a directly Attorney Docket No. 35327-522001 WO responsive fluorophore and an indirectly responsive fluorophore. In various embodiments, λ ₂ falls within the emission spectrum of both a directly responsive fluorophore and an indirectly responsive fluorophore.

Aspects of the present subject matter provide FRSs whose emission spectra change (e.g., the shape of the emission spectra change) in response to urea binding. In various embodiments, the ratio of intensities at two chosen wavelengths of an FRS's emission spectrum changes upon urea binding.

In various embodiments, the emission spectra of two or more fluorophores contributes to Ιχι and/or _¾2 . In some embodiments, the emission spectrum of a directly responsive fluorophore contributes to I _\\ and/or I%2 and the emission spectrum of an indirectly responsive fluorophore contributes to I _\\ and/or _¾2 . In certain embodiments, a directly responsive fluorophore contributes to I _\\ and the emission spectrum of an indirectly responsive fluorophore contributes to i _¾2 . In some embodiments, a directly responsive fluorophore contributes to ½ and the emission spectrum of an indirectly responsive fluorophore contributes to In various embodiments, both the emission spectrum of a directly responsive fluorophore and the emission spectrum of an indirectly responsive fluorophore contributes to In some embodiments, both the emission spectrum of a directly responsive fluorophore and the emission spectrum of an indirectly responsive fluorophore contributes to

In some embodiments, the directly responsive fluorophore is Alexa532 and emission intensity is measured at a wavelength or range of wavelengths between about 400 nm and 1000 nm (e.g. including a wavelength of about 530, 531, 532, 534, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, or 570 nm), and wherein the indirectly responsive fluorophore is Acrylodan and emission intensity is measured at a wavelength or range of wavelengths between about 400 nm and 1000 nm (e.g. including 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 45, 496, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, or 510 nm). In some embodiments, the directly responsive fluorophore is Acrylodan and emission intensity is measured at a wavelength or range of wavelengths between about 400 nm and lOOOnm (e.g., including a wavelength of about 480,481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, or 500 nm), and wherein the Attorney Docket No. 35327-522001 WO indirectly responsive fluorophore is Alexa532 and emission intensity is measured at a wavelength or range of wavelengths between about 400 nm and lOOOnm (e.g., including a wavelength of about 540, 541, 542, 543, 544, 545, 5546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, or 560 nm). In some embodiments, the directly responsive fluorophore is Badan and emission intensity is measured at a wavelength or range of wavelengths between about 400 nm and lOOOnm (e.g., including a wavelength of about 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, or 495 nm), and wherein the indirectly responsive fluorophore is Alexa532 and emission intensity is measured at a wavelength or range of wavelengths between about 400 nm and lOOOnm (e.g., including a wavelength of about 545, 546, 547, 548, 549, 550, 51, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, or 565 nm). In some embodiments, the directly responsive fluorophore is Acrylodan and emission intensity is measured at a wavelength or range of wavelengths between about 400 nm and lOOOnm (e.g., including a wavelength of about 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520 nm), and wherein the indirectly responsive fluorophore is Alexa532 and emission intensity is measured at a wavelength or range of wavelengths between about 400 nm and lOOOnm (e.g., including a wavelength of about 540, 541, 542, 543, 544, 545, 5546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, or 560 nm). In some embodiments, the directly responsive fluorophore is Badan and emission intensity is measured at a wavelength or range of wavelengths between about 400 nm and lOOOnm (e.g., including a wavelength of about 545, 546, 547, 548, 549, 550, 51, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, or 565 nm), and wherein the indirectly responsive fluorophore is Alexa532 and emission intensity is measured at a wavelength or range of wavelengths between about 400 nm and lOOOnm (e.g., including a wavelength of about 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520 nm). In some embodiments, the directly responsive fluorophore is Badan and emission intensity is measured at a wavelength or range of wavelengths between about 400 nm and lOOOnm (e.g., including a wavelength of about 480,481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, or 500 nm), and wherein the indirectly responsive fluorophore is Alexa532 and emission intensity is measured at a wavelength or range of wavelengths between about 400 nm and lOOOnm (e.g., including a wavelength of about 540, 541, 542, 543, 544, 545, 5546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, or 560 nm). In some embodiments, the directly responsive Attorney Docket No. 35327-522001 WO fluorophore is Acrylodan and emission intensity is measured at a wavelength or range of wavelengths between about 400 nm and lOOOnm (e.g., including a wavelength of about 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 489, or 490 nm), and wherein the indirectly responsive fluorophore is Alexa532 and emission intensity is measured at a wavelength or range of wavelengths between about 400 nm and lOOOnm (e.g., including a wavelength of about 540, 541, 542, 543, 544, 545, 5546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, or 560 nm). In some embodiments, the directly responsive fluorophore is Badan and emission intensity is measured at a wavelength or range of wavelengths between about 400 nm and lOOOnm (e.g., including a wavelength of about 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, or 495 nm), and wherein the indirectly responsive fluorophore is Texas Red and emission intensity is measured at a wavelength or range of wavelengths between about 400 nm and lOOOnm (e.g., including a wavelength of about 600, 601, 602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, or 620 nm). In some embodiments, the directly responsive fluorophore is Oregon Green and emission intensity is measured at a wavelength or range of wavelengths between about 400 nm and lOOOnm (e.g., including a wavelength of about 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, or 535 nm), and wherein the indirectly responsive fluorophore is Pacific Blue and emission intensity is measured at a wavelength or range of wavelengths between about 400 nm and lOOOnm (e.g., including a wavelength of about 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, or 465 nm). In some embodiments, the directly responsive fluorophore is Alexa532 and emission intensity is measured at a wavelength or range of wavelengths between about 400 nm and lOOOnm (e.g., including a wavelength of about 550, 551, 552, 553, 554, 555, 56, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, or 570 nm), and wherein the indirectly responsive fluorophore is Badan and emission intensity is measured at a wavelength or range of wavelengths between about 400 nm and lOOOnm (e.g., including a wavelength of about 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, or 495 nm). In some embodiments, the directly responsive fluorophore is Alexa532 and emission intensity is measured at a wavelength or range of wavelengths between about 400 nm and lOOOnm (e.g., including a wavelength of about 550, 551, 552, 553, 554, 555, 56, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, or 570 nm), and wherein the indirectly responsive fluorophore is Acrylodan and emission Attorney Docket No. 35327-522001 WO intensity is measured at a wavelength or range of wavelengths between about 400 nm and lOOOnm (e.g., including a wavelength of about 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, or 495 nm).

Various embodiments, the urea-binding protein comprises a cysteine at the position of its amino acid sequence that aligns with position 26, 27, 30, 95, or 186 of csUBP7 (SEQ ID NO: 18 or 218) when the amino acid sequence of the urea-binding protein is aligned with the amino acid sequence of csUBP7 using the ClustalW alignment program, and wherein the Acrylodan or the Badan is covalently attached to the cysteine. In some embodiments, the Alexa532 or the Texas Red is attached to the N-terminus or the C-terminus of the urea- binding protein via a fluorophore attachment motif. In a non-limiting example, the urea- binding protein comprises amino acids in the sequence of SEQ ID NO: 98. Alternatively, the urea-binding protein comprises a cysteine at the position of its amino acid sequence that aligns with position 186 of csUBP7 (SEQ ID NO: 18 or 218) when the amino acid sequence of the urea-binding protein is aligned with the amino acid sequence of csUBP7 using the ClustalW alignment program, and wherein the Oregon Green or the Alexa532 is covalently attached to the cysteine. In some embodiments, the Pacific Blue, the Acrylodan, or the Badan is attached to the N-terminus or the C-terminus of the urea-binding protein via a fluorophore attachment motif.

In various embodiments, the change in the fluorescent property of the directly responsive fluorophore comprises (i) a bathochromic or hypsochromic shift in the emission or excitation spectrum thereof; and/or (ii) a change in the ratio of radiative to non-radiative emission rates thereof.

In embodiments, the directly responsive fluorophore comprises a donor fluorophore and the indirectly responsive fluorophore comprises an acceptor fluorophore. In some embodiments, the emission intensity of the donor fluorophore decreases and the emission intensity of the acceptor fluorophore increases upon urea binding to the urea-binding protein when the donor fluorophore is contacted with radiation within the excitation spectrum of the donor fluorophore. In some embodiments, the emission intensity of the donor fluorophore increases and the emission intensity of the acceptor fluorophore decreases upon urea binding to the urea-binding protein when the donor fluorophore is contacted with radiation within the excitation spectrum of the donor fluorophore. In some embodiments, the emission intensities of the donor fluorophore and the acceptor fluorophore both decrease upon urea binding to the urea-binding protein when the donor fluorophore is contacted with radiation within the Attorney Docket No. 35327-522001 WO excitation spectrum of the donor fluorophore. In some embodiments, the emission intensity of the donor fluorophore decreases and the emission intensity of the acceptor fluorophore increases, decreases, or remains about the same upon urea binding to the urea-binding protein when the donor fluorophore is contacted with radiation within the excitation spectrum of the donor fluorophore. In some embodiments, the emission intensity of the donor fluorophore increases, decreases, or remains about the same and the emission intensity of the acceptor fluorophore decreases upon urea binding to the urea-binding protein when the donor fluorophore is contacted with radiation within the excitation spectrum of the donor fluorophore. In some embodiments, the emission intensities of the donor fluorophore and the acceptor fluorophore both increase upon urea binding to the urea-binding protein when the donor fluorophore is contacted with radiation within the excitation spectrum of the donor fluorophore. In some embodiments, the emission intensity of the donor fluorophore increases, decreases, or remains about the same and the emission intensity of the acceptor fluorophore increases upon urea binding to the urea-binding protein when the donor fluorophore is contacted with radiation within the excitation spectrum of the donor fluorophore. In some embodiments, the emission intensity of the donor fluorophore increases and the emission intensity of the acceptor fluorophore increases, decreases, or remains about the same upon urea binding to the urea-binding protein when the donor fluorophore is contacted with radiation within the excitation spectrum of the donor fluorophore.

In embodiments the directly responsive fluorophore comprises an acceptor fluorophore and the indirectly responsive fluorophore comprises a donor fluorophore. In some embodiments, the emission intensity of the donor fluorophore decreases and the emission intensity of the acceptor fluorophore increases, decreases, or remains about the same upon urea binding to the urea-binding protein when the donor fluorophore is contacted with radiation within the excitation spectrum of the donor fluorophore. In some

embodiments, the emission intensity of the donor fluorophore increases and the emission intensity of the acceptor fluorophore increases, decreases, or remains about the same upon urea binding to the urea-binding protein when the donor fluorophore is contacted with radiation within the excitation spectrum of the donor fluorophore. In some embodiments, the emission intensity of the donor fluorophore remains about the same and the emission intensity of the acceptor fluorophore decreases upon urea binding to the urea-binding protein when the donor fluorophore is contacted with radiation within the excitation spectrum of the donor fluorophore. In some embodiments, the emission intensity of the donor fluorophore Attorney Docket No. 35327-522001 WO decreases and the emission intensity of the acceptor fluorophore increases, decreases, or remains about the same upon urea binding to the urea-binding protein when the donor fluorophore is contacted with radiation within the excitation spectrum of the donor fluorophore. In some embodiments, the emission intensity of the donor fluorophore increases and the emission intensity of the acceptor fluorophore increases, decreases, or remains about the same upon urea binding to the urea-binding protein when the donor fluorophore is contacted with radiation within the excitation spectrum of the donor fluorophore. In some embodiments, the emission intensity of the donor fluorophore remains about the same and the emission intensity of the acceptor fluorophore increases upon urea binding to the urea- binding protein when the donor fluorophore is contacted with radiation within the excitation spectrum of the donor fluorophore. In some embodiments, the emission intensity of the donor fluorophore decreases and the emission intensity of the acceptor fluorophore increases upon urea binding to the urea-binding protein when the donor fluorophore is contacted with radiation within the excitation spectrum of the donor fluorophore. In some embodiments, the emission intensity of the donor fluorophore increases and the emission intensity of the acceptor fluorophore remains about the same, increases, or decreases upon urea binding to the urea-binding protein when the donor fluorophore is contacted with radiation within the excitation spectrum of the donor fluorophore.

In instances in which an emission intensity increases, the increase may be, e.g., between about 0.1% to 10%, 10% to 50%, or 50% to 100%, or at least about 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 50%, 75%, 100%, 2-fold, 3-fold, 4-fold, 5-fold, 6- fold, 7-fold, 8-fold, 9-fold, or 10-fold. In instances in which an emission intensity decreases, the decrease may be, e.g., a decrease of between about at least about 0.1% to 10%, 10% to 50%, or 50% to 00%, or at least about 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90%. In various embodiments in which both the emission intensity of the donor fluorophore and the acceptor fluorophore increases, then the increases are not equal. In certain embodiments in which both the emission intensity of the donor fluorophore and the acceptor fluorophore decreases, then the decreases are not equal.

In certain embodiments, the indirectly responsive fluorophore is attached to the urea- binding protein via a covalent bond. Various approaches for attaching reporter groups such as directly and indirectly responsive fluorophores to a polypeptide such as a urea-binding protein are described herein. In some embodiments, the covalent bond comprises a disulfide Attorney Docket No. 35327-522001 WO bond, a thioester bond, a thioether bond, an ester bond, an amide bond, or a bond that has been formed by a click reaction.

In some embodiments, the indirectly responsive fluorophore is attached to the urea- binding protein via a non-covalent bond. In certain embodiments, the indirectly responsive fluorophore is attached to a cysteine or a lysine of the urea-binding protein.

In various embodiments, the indirectly responsive fluorophore is attached to the N- terminus or the C-terminus of the protein. In some embodiments, the indirectly responsive fluorophore is attached to the N-teiminus or the C-terminus of the protein via a fluorophore attachment motif.

In some embodiments, fluorophore attachment motif comprises a polypeptide.

Various embodiments may be used to link a fluorophore with a urea-binding protein. In some embodiments, the polypeptide comprises a stretch of at least 50, 60, 70, 80, 90, or 100 amino acids. In a non-limiting example, the polypeptide comprises amino acids in the sequence of βΖίί (SEQ ID NO: 105). In another non-limiting example, the polypeptide comprises a stretch of at least 50, 60, 70, 80, 90, or 100 amino acids in a sequence that is at least about 85%, 90%, 95%, or 99% identical to the amino acid sequence of E. coli

thioredoxin (ecTRX; SEQ ID NO: 229).

In some embodiments, the directly responsive fluorophore is attached to the urea- binding protein via a covalent bond. In various embodiments, the covalent bond comprises a disulfide bond, a thioester bond, a thioether bond, an ester bond, an amide bond, or a bond that has been formed by a click reaction. In directly responsive fluorophore is attached to a cysteine or a lysine of the protein.

In some embodiments, an overlap of the emission spectrum of the donor fluorophore and the excitation spectrum of the acceptor fluorophore increases upon urea binding. In certain embodiments, the directly responsive fluorophore comprises the donor fluorophore, and the increase results from a bathochromic shift in the emission spectrum of the donor fluorophore. Alternatively, the directly responsive fluorophore comprises the acceptor fluorophore, and the increase results from a hypsochromic shift in the excitation spectrum of the acceptor fluorophore.

In various embodiments, an overlap of the emission spectrum of the donor fluorophore and the excitation spectrum of the acceptor fluorophore decreases upon urea binding. In some embodiments, the directly responsive fluorophore comprises the donor fluorophore, and the decrease results from a hypsochromic shift in the emission spectrum of Attorney Docket No. 35327-522001 WO the donor fluorophore. In certain embodiments, the directly responsive fluorophore comprises the acceptor fluorophore, and the decrease results from a bathochromic shift in the excitation spectrum of the acceptor fluorophore.

In some embodiments, the directly responsive fluorophore has a monochromatic spectral change upon urea binding. Alternatively, the directly responsive fluorophore has a dichromatic spectral change upon urea binding.

In certain embodiments, the emission intensity of the donor fluorophore and/or the acceptor fluorophore increases in two phases as urea concentration increases.

In various embodiments, the ratio of radiative to non-radiative emission or intensity of the directly responsive fluorophore increases by at least about 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 50%, 75%, 100%, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8- fold, 9-fold, or 10-fold upon urea binding to the urea-binding protein. Alternatively, the ratio of radiative to non-radiative emission or intensity of the directly responsive fluorophore decreases by at least about 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 50%, 75%, 90%, 95%, or 99% upon urea binding to the urea-binding protein.

In embodiments, the directly responsive fluorophore and the indirectly responsive fluorophore are not a naphthalene derivative. In some embodiments, the directly responsive fluorophore and the indirectly responsive fluorophore are not Prodan, Acrylodan, or Badan. In certain embodiments, the directly responsive fluorophore is not a naphthalene derivative. In some embodiments, the directly responsive fluorophore is not Prodan, Acrylodan, or Badan.

In various embodiments, the directly responsive fluorophore comprises xanthene, a xanthene derivative, fluorescein, a fluorescein derivative, coumarin, a coumarin derivative, cyanine, a cyanine derivative, rhodamine, a rhodamine derivative, phenoxazine, a phenoxazine derivative, squaraine, a squaraine derivative, coumarin, a coumarin derivative, oxadiazole, an oxadiazole derivative, anthracene, an anthracene derivative, a

boradiazaindacine (BODIPY) family fluorophore, pyrene, a pyrene derivative, acridine, an acridine derivative, arylmethine, an arylmethine derivative, tetrapyrrole, or a tetrapyrrole derivative. In some embodiments, the directly responsive fluorophore comprises fluorescein or a derivative thereof.

In some embodiments, the directly responsive fluorophore and/or the indirectly responsive fluorophore comprises a fluorescent protein. In various embodiments, the directly responsive fluorophore and/or the indirectly responsive fluorophore comprises an organic Attorney Docket No. 35327-522001 WO compound having a molecular weight less than about 2000 Da (e.g., 5- iodoacetamidofluorescein (5-IAF) or 6-iodoacetamidofluorescein (6-IAF), rhodamine, Oregon Green, eosin, Texas Red, indocarbocyanine, oxacarbocyanine, thiacarbocyanine, merocyanine, Badan, Acrylodan, IAEDANS, comprising 3-cyano-7-hydroxycoumarin, 7- hydroxycoumarin-3-carboxylic acid, 6,8-difluoro-7-hydroxy- 4-methylcoumarin, or 7-amino-

4- methylcoumarin, pyridyloxazole, nitrobenzoxadiazole, benzoxadiazole, DRAQ5, DRAQ7, or CyTRAK Orange, cascade blue, Nile red, Nile blue, cresyl violet, oxazine 170, proflavin, acridine orange, acridine yellow, auramine, crystal violet, malachite green, porphin, phthalocyanine, bilirubin, pyrene, N,N'-dimethyl-N-(iodoacetyl)-N'-(7-nitrobenz-2-ox- a- 1,3- diazol-4-yl)ethylenediamide (NBD), N-((2-(iodoacetoxy)ethyl)-N-methy- l)amino-7- nitrobenz-2-oxa-l,3-diazole (NBDE), JPW4039, JPW4042, JPW4045, Pacific Blue, CPM, N,N'-Dimethyl-N-(Iodoacetyl)-N'-(7-Nitrobenz-2-Oxa- 1 ,3 -Diazol-4-yl)Ethylenediamine (IANBD), 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin (CPM), BODIPY 499, BODIPY 507/545, BODIPY 499/508, Alexa 432, Alexa488, Alexa532, Alexa546, Cy5, or 1- (2-maleimidylethyl)-4-(5-(4-methoxyphenyl)oxazol-2-yl)pyridi nium methanesulfonate (PyMPO maleimide) (PyMPO)). Numerous combinations of directly responsive

fluorophores and indirectly responsive fluorophores are possible. For example, in various non-limiting examples, (a) the donor fluorophore comprises Pacific Blue and the acceptor fluorophore comprises 5-IAF or 6-iodoacetamidofluorescein (6-IAF); (b) the donor fluorophore comprises Pacific Blue and the acceptor fluorophore comprises Oregon Green; (c) the donor fluorophore comprises IAEDANS and the acceptor fluorophore comprises 5- IAF or 6-IAF; (d) the donor fluorophore comprises acrylodan and the acceptor fluorophore comprises Alexa532; (e) the donor fluorophore comprises acrylodan and the acceptor fluorophore comprises 5-IAF or 6-IAF; (f) the donor fluorophore comprises acrylodan and the acceptor fluorophore comprises Pacific Blue or YFP; (g) the donor fluorophore comprises

5- IAF or 6-IAF and the acceptor fluorophore comprises Pacific Blue; (h) the donor fluorophore comprises badan and the acceptor fluorophore comprises 5-IAF or 6-IAF; or (i) the donor fluorophore comprises badan and the acceptor fluorophore comprises Alexa532.

Aspects also include a biosensor for a urea comprising a urea-binding protein, a directly responsive fluorophore and an indirectly responsive fluorophore, the directly responsive and the indirectly responsive fluorophores being located at two distinct sites of the urea-binding-protein, wherein (i) the directly responsive fluorophore is a donor fluorophore and the indirectly responsive fluorophore is an acceptor fluorophore; or (ii) the directly Attorney Docket No. 35327-522001 WO responsive fluorophore is an acceptor fluorophore and the indirectly responsive fluorophore is an donor fluorophore, and wherein if the acceptor fluorophore comprises ruthenium or osmium, then the acceptor fluorophore is not attached to the amino group of the N-terminus of the urea-binding protein.

Any of the urea-binding proteins disclosed herein, as well as others, may be included in the biosensors and methods that are provided.

Aspects of the present subject matter also provide a method for constructing a biosensor, comprising: (a) providing a urea-binding protein; (b) identifying at least one putative allosteric, endosteric, or peristeric site of the urea-binding based a structure of the urea-binding protein; (c) mutating the urea-binding protein to substitute an amino acid at the at least one putative allosteric, endosteric, or peristeric site of the second protein with a cysteine; (d) conjugating a donor fluorophore or an acceptor fluorophore to the cysteine to produce single labeled biosensor; (e) detecting whether there is a spectral shift or change in emission intensity of the single labeled biosensor upon urea binding when the donor fluorophore or the acceptor fluorophore is fully excited; and (f) if a spectral shift or change in emission intensity is detected in (e), attaching a donor fluorophore to the second protein if an acceptor fluorophore is attached to the cysteine, and attaching an acceptor fluorophore to the second protein if an acceptor fluorophore is attached to the cysteine.

In various embodiments, the urea-binding protein has been identified by (i) selecting a first protein having a known amino acid sequence (seed sequence), wherein the first protein is known to bind a urea; (ii) identifying a second protein having an amino acid sequence (hit sequence) with at least 15% sequence identity to the seed sequence; (iii) aligning the seed amino acid sequence and the hit sequence, and comparing the hit sequence with the seed sequence at positions of the seed sequence that correspond to at least 5 primary

complementary surface (PCS) amino acids, wherein each of the at least 5 PCS amino acids has a hydrogen bond interaction or a van der Waals interaction with urea when urea is bound to the first protein; and (iv) identifying the second protein to be a urea-binding protein if the hit sequence comprises at least 5 amino acids that are consistent with the PCS.

In some embodiments, the spectral shift comprises a monochromatic fluorescence intensity change or a dichromatic spectral shift.

Also provided is a method of converting a biosensor that shows a monochromatic response upon urea binding into a biosensor with a dichromatic response upon urea binding, the method comprising (a) selecting a biosensor that exhibits a monochromatic response upon Attorney Docket No. 35327-522001 WO urea binding, wherein the biosensor comprises a urea-binding protein and a first reporter group; and (b) attaching a second reporter group to the biosensor, wherein the second reporter group has (i) an excitation spectrum that overlaps with the emission spectrum of the first reporter group; or (ii) an emission spectrum that overlaps with the excitation spectrum of the first reporter group.

Also provided is a method of increasing a dichromatic response of a biosensor to urea binding, the method comprising (a) selecting a biosensor that exhibits a dichromatic response upon urea binding, wherein the biosensor comprises a urea-binding protein and a first reporter group; and (b) attaching a second reporter group to the biosensor, wherein the second reporter group has (i) an excitation spectrum that overlaps with the emission spectrum of the first reporter group; or (ii) an emission spectrum that overlaps with the excitation spectrum of the first reporter group.

In some embodiments, the second reporter group is within about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 4, 6, 8, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 125, 150, or 200 angstroms (A) of the first reporter group regardless of whether ligand is bound to the biosensor. Suitable distances may be determined in part by the distance-dependence of the energy transfer between a given donor-acceptor pair {see, e.g. J.R. Lakowicz, 2006,

Principles of Fluorescence Spectroscopy, Springer, incorporated herein by reference). In some embodiments, when the urea is bound to the biosensor, the average distance between the first reporter group and the second reporter group changes by less than about 5, 4, 3, 2, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.05, or 0.01 angstroms (A) compared to when urea is not bound to the urea-binding protein.

In various embodiments, if the acceptor fiuorophore comprises palladium, platinum, ruthenium, or osmium, then the acceptor fiuorophore is not attached to the amino group of the N-terminus of the ligand-binding protein. In some embodiments, the acceptor fiuorophore does not comprise [Ru(bpy)3] ²⁺ , [Ru(Ph ₂ phen)3] ^2÷ , [Ru(bpy) ₂ (dcbpy)] ²⁺ , or [Ru(bpy) ₂ (phen-ITC)] ²⁺ , where bpy is 2,2'-bipyridine _s phen is 1,10-phenanthroline, dcbpy is 4,4'-dicarboxy-2,2'-bipyridine, and ITC is isothiocyanate. In certain embodiments, the biosensor does not comprise an E. coli glutamine-binding protein with Acrylodan attached to 179C. In some embodiiments, the biosensor does not comprise E. coli urea-binding protein with Acrylodan attached to 255C. Attorney Docket No. 35327-522001 WO tgmFRET Biosensors

While ngmFRET is preferred to tgmFRET, tgmFRET may be used alternatively or in addition to ngmFRET in certain embodiments.

In various embodiments, the biosensor comprises multiple reporter groups, including a first reporter group and a second reporter group. For example, the first reporter group may comprise a donor fluorophore and the second reporter group may comprise an acceptor fluorophore. In certain embodiments, FRET is detectable by a change in the fluorescence of the acceptor fluorophore or by a decrease in of donor fluorophore fluorescence. In various embodiments, the donor fluorophore, and/or the acceptor fluorophore is fluorescent. In some embodiments, both the donor fluorophore and the acceptor fluorophore are fluorescent.

In various embodiments, the angle and/or distance between the donor fluorophore and the acceptor fluorophore changes upon urea binding. In some embodiments, neither the donor fluorophore nor the acceptor fluorophore is directly responsive to urea binding. In some embodiments the donor fluorophore and/or the acceptor fluorophore is attached to the N-terminus or the C-terminus of the urea-binding protein (e.g., directly or via a fluorophore attachment motif). In certain embodiments, the donor fluorophore and/or the acceptor fluorophore is attached to a fluorophore attachment motif. For example, the fluorophore attachment motif may be conjugated to the N-terminus or the C-terminus of the urea-binding protein.

In some embodiments, the donor fluorophore and/or the acceptor fluorophore comprises a fluorescent protein. In various embodiments, the donor fluorophore and/or the acceptor fluorophore comprises an organic compound having a molecular weight less than about 2000 Da (e.g., 5-iodoacetamidofluorescein (5-IAF) or 6-iodoacetamidofluorescein (6- IAF), rhodamine, Oregon Green, eosin, Texas Red, indocarbocyanine, oxacarbocyanine, thiacarbocyanine, merocyanine, Badan, Acrylodan, IAEDANS, comprising 3-cyano-7- hydroxycoumarin, 7-hydroxycoumarin-3-carboxylic acid, 6,8-difluoro-7-hydroxy- 4- methylcoumarin, or 7-amino-4-methylcoumarin, pyridyloxazole, nitrobenzoxadiazole, benzoxadiazole, DRAQ5, DRAQ7, or CyTRAK Orange, cascade blue, Nile red, Nile blue, cresyl violet, oxazine 170, proflavin, acridine orange, acridine yellow, auramine, crystal violet, malachite green, porphin, phthalocyanine, bilirubin, pyrene, N,N'-dimethyl-N- (iodoacetyl)-N'-(7-nitrobenz-2-ox- a-l,3-diazol-4-yl)ethylenediamide (NBD), N-((2- (iodoacetoxy)ethyl)-N-methy- l)amino-7-nitrobenz-2-oxa-l,3-diazole (NBDE), Acrylodan, JPW4039, JPW4042, JPW4045, Oregon Green, Pacific Blue, CPM, N,N'-Dimethyl-N- Attorney Docket No. 35327-522001 WO

(Iodoacetyl)-N'-(7-Nitrobenz-2-Oxa- 1 ,3-Diazol-4-yl)Ethylenediamine (IANBD), 7- diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin (CPM), BODIPY 499, BODIPY 507/545, BODIPY 499/508, Alexa 432, Alexa488, Alexa532, Alexa546, Cy5, or l-(2- maleimidylethyl)-4-(5-(4-methoxyphenyl)oxazol-2- yl)pyridinium methanesulfonate (PyMPO maleimide) (PyMPO)). For example, the organic compound is a fluorophore. Numerous combinations of donor and acceptor fluorophores are possible.

Fluorophore Attachment Motifs

Aspects of the present subject matter include the use of one or more fluorophore attachment motifs to attach one or more reporter groups to a urea-binding protein. For example, a reporter group may be attached to a fluorophore attachment motif that is attached to the N-terminus or the C-terminus of the urea-binding protein.

In various implementations, the fluorophore attachment motif comprises a polypeptide. In some embodiments, the polypeptide comprises amino acids in the βΖίί amino acid sequence (SEQ ID NO: 105).

In some embodiments, the polypeptide comprises a stretch of at least 50, 60, 70, 80, 90, or 100 amino acids in a sequence that is at least about 85%, 90%, 95%, or 99% identical to the amino acid sequence of E. coli thioredoxin (ecTRX; SEQ ID NO: 229). In some embodiments, the polypeptide is a mutant of ecTRX comprising a D3X, K4X, K19X, D27X, K37X, K53X, K58X, K70X, R74X, K83X, K91X, K97X, or K101X mutation, or any combination thereof, wherein X is any amino acid, and wherein each ecTRX amino acid position is numbered as in SEQ ID NO: 229. In certain embodiments, the polypeptide is a mutant of ecTRX comprising a D3A, K4R, K4Q, K19R, K19Q, D27A, K37R, K53M, K53R, K58M, K70R, R74C, K83R, K91R, K97R, or K101R mutation, or any combination thereof, wherein each ecTRX amino acid position is numbered as in SEQ ID NO: 229.

In non-limiting examples, the polypeptide comprises amino acids in the sequence set forth as any one of SEQ ID NOS: 230-247.

In certain embodiments, the polypeptide comprises (a) at least 1, 2, or 3 thiol groups; (b) at least 1, 2, or 3 cysteines that each comprise a sulfhydryl group; (c) at least 1, 2, or 3 primary amine groups; and/or (d) at least 1, 2, or 3 lysines that each comprise a primary amine. In some embodiments there is no disulfide bond between cysteines within the amino acid sequence of the polypeptide. Attorney Docket No. 35327-522001 WO

In some embodiments, the polypeptide comprises a hexahistidine tag. In some embodiments, the hexahisidine tag is attached to another portion of the polypeptide via a GGS linker.

Exemplary Methods of Using Biosensors Provided Herein

Aspects of the present subject matter provide a method of assaying for a ligand in a sample. The method may include contacting the sample with a biosensor disclosed herein under conditions such that the ligand-binding protein of the biosensor binds to the ligand if ligand is present in the sample. The method also comprises detecting (i) whether a signal is produced by a reporter group of the biosensor; and/or (ii) the a signal produced by a reporter group of the biosensor. In a non-limiting example, a reporter group of the biosensor is fluorescent, and the method further comprises contacting the reporter group with

electromagnetic radiation having a wavelength that comprises a wavelength within the band of excitation wavelengths of the reporter group.

In various embodiments, the method further comprises (i) comparing a signal produced by a reporter group of the biosensor when the biosensor is contacted with the sample with a signal produced by a control sample containing a known quantity of ligand (e.g., ligand at a concentration of about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, 100, 125, 150, 175, or 200 mM, or a series of control samples having

concentrations within the range of about 0.5 mM to about 100 mM or 0.5 mM to about 200 mM); and (ii) detecting the presence or absence of ligand in the sample based on this comparison. In embodiments the control sample lacks urea (e.g., the contentration of urea is 0 mM). Alternatively or in addition, the method further comprises (i) comparing a signal produced by a reporter group of the biosensor when the biosensor is contacted with the sample with signals produced by a series of control samples containing known quantities of ligand; and (ii) determining the quantity of ligand in the sample based on this comparison. In some embodiments, the series of control samples comprises at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 control samples, and wherein each control sample comprises a different quantity of ligand. Alternatively or in addition, the method further comprises determining the concentration of a ligand in a sample, wherein determining the concentration of the ligand in the sample comprises comparing the signal to a standard hyperbolic ligand binding curve to determine the concentration of the ligand in the test sample, wherein the standard hyperbolic ligand binding curve is prepared by measuring the signal produced by the reporter group of the Attorney Docket No. 35327-522001 WO biosensor when the biosensor is contacted with control samples containing known concentrations of ligand. In various embodiments, the method comprises (i) measuring a ratiometric change (AR) and/or an intensity change (ΔΙ) of a signal produced by the reporter group. In some embodiments, the method includes quantitating the level of ligand present in the sample.

In various embodiments, the ligand comprises urea and the ligand-binding protein comprises a urea-binding protein.

Aspects of the present subject matter also provide a method of assaying for multiple ligands in a sample, wherein the multiple ligands comprise a first ligand and a second ligand. Such a method may include contacting the sample with (i) a first biosensor a first ligand provided herein and (ii) a second biosensor for the second ligand, under conditions such that the ligand-binding protein of the first biosensor binds to the first ligand, if the first ligand is present in the sample, and detecting (i) a signal, e.g. magnitude of the signal, produced by a reporter group of the first biosensor, or (ii) whether a signal is produced by a reporter group of the first biosensor. In some embodiments, the second biosensor is also a biosensor provided herein, and the second biosensor is contacted with the second ligand under conditions such that the ligand-binding protein of the second biosensor binds to the second ligand it is present in the sample. The method may further comprise detecting (i) a signal, e.g. magnitude of the signal, produced by a reporter group of the second biosensor, or (ii) whether a signal is produced by a reporter group of the second biosensor.

In some embodiments, the signal produced by the reporter group of the first biosensor is different than the signal produced by the reporter group of the second biosensor. In a non- limiting example, the reporter group of the first biosensor and the reporter group of the second biosensor are each fluorescent, and the peak emission wavelength of the reporter group of the first biosensor is at least about 10, 25, 50, 75, or 100 nm greater or lower than the peak emission wavelength of the reporter group of the second biosensor.

Non-limiting examples of biosensors that may be used as the second biosensor include biosensors with ligand-binding proteins comprising a GGBP (e.g., an E. coli GGBP) or a derivative or mutant thereof; (ii) an E. coli arabinose binding protein (e.g., an E. coli arabinose binding protein) or a derivative or mutant thereof; (iii) a dipeptide binding protein (e.g., an E. coli dipeptide binding protein) or a derivative or mutant thereof; (iv) a histidine binding protein (e.g., an E. coli, histidine binding protein) or a derivative or mutant thereof; (v) a ribose binding protein (e.g., an E. coli ribose binding protein) or a derivative or mutant Attorney Docket No. 35327-522001 WO thereof; (vi) a sulfate binding protein (e.g., an E. coli sulfate binding protein) or a derivative or mutant thereof; (vii) a maltose binding protein (e.g., an E. coli maltose binding protein) or a derivative or mutant thereof; (viii) a glutamine binding protein (e.g., an E. coli glutamine binding protein) or a derivative or mutant thereof; (ix) a glutamate/aspartate binding protein (e.g., an is. coli glutamate/aspartate binding protein) or a derivative or mutant thereof; (x) a phosphate binding protein (e.g., an E. coli phosphate binding protein) or a derivative or mutant thereof; or (xi) an iron binding protein [e.g., a Haemophilus influenza (H. influenzae) iron binding protein] or a derivative or mutant thereof. For example, the second biosensor comprises an E. coli GGBP having a Y10C, Y10A, DMA, D14Q, D14N, D14S, D14T, D14E, D14H, D14L, D14Y, D14F, D14C, N15C, F16L, F16A, F16Y, F16C, N91A, K92C, E93C, S112A, S115A, E149C, E149K, E149Q, E149S, H152A, H152F, H152Q, H152N, H152C, D154A, D154C, D154N, A155S, A155H, A155L, A155F, A155Y, A155N, A155K, A155M, A155W, A155Q, A155C, R158A, R158K, R158C, M182C, M182W, W183C, W183A, N211F, N211W, N211K, N211Q, N211S, N211H, N211M, N211C, D212C, D236A, D236N, L238C, L255C, N256A, N256D, D257C, V293C, P294C, or V296C mutation (e.g., comprising 1, 2, 3, 4, 5 or more of these mutations), wherein each amino acid position is numbered as in (SEQ ID NO: 225); (ii) an E. coli arabinose binding protein having a D257C, F23C, K301C, L253C, or L298C mutation (e.g., comprising 1, 2, 3, 4, or 5 of these mutations) (see, e.g., U.S. Patent Application Publication No. 2004/0118681, the entire contents of which are incorporated herein by reference) (see, e.g., U.S. Patent Application Publication No. 2004/0118681, the entire contents of which are incorporated herein by reference); (iii) an E. coli dipeptide binding protein having a D450C, K394C, R141C, Sl l lC, T44C, or W315C mutation (e.g., comprising 1 , 2, 3, 4, 5 or 6 of these mutations) (see, e.g., U.S. Patent Application Publication No. 2004/0118681, the entire contents of which are incorporated herein by reference); (iv) an E. coli, histidine binding protein having a E167C, K229C, V163C, Y230C, F231C, Y88C mutation (e.g., comprising 1, 2, 3, 4, 5 or 6 of these mutations) (see, e.g., U.S. Patent Application Publication No. 2004/0118681, the entire contents of which are incorporated herein by reference); (v) an E. coli ribose binding protein having a T135C, D165C, E192C, A234C, L236C, or L265C mutation (e.g.,

comprising 1, 2, 3, 4, 5 or 6 of these mutations) (see, e.g., U.S. Patent Application Publication No. 2004/0118681, the entire contents of which are incorporated herein by reference); (vi) an E. coli sulfate binding protein having a L65C, N70C, Q294C, R134C, W290C, or Y67C mutation (e.g., comprising 1, 2, 3, 4, 5 or 6 of these mutations) (see, e.g., U.S. Patent Attorney Docket No. 35327-522001 WO

Application Publication No. 2004/0118681 the entire content of which is incorporated herein by reference); (vii) an E. coli maltose binding protein having a D95C, F92C, E163C, G174C, I329C, or S233C mutation {e.g., comprising 1, 2, 3, 4, 5 or 6 of these mutations) {see, e.g., U.S. Patent Application Publication No. 2004/0118681 the entire content of which is incorporated herein by reference); (viii) an E. coli glutamine binding protein having a N160C, F221C, K219C, L162C, W220C, Y163C, or Y86C mutation {e.g., comprising 1, 2, 3, 4, 5 or more of these mutations) {see, e.g., U.S. Patent Application Publication No.

2004/ 0118681 the entire content of which is incorporated herein by reference) ; (ix) an E. coli glutamate/aspartate binding protein having a A207C, A210C, El 19C, F126C, F131C, F270C, G211C, K268C, Q123C, or T129C mutation {e.g., comprising 1, 2, 3, 4, 5 or more of these mutations) {see, e.g., U.S. Patent Application Publication No. 2004/0118681 the entire content of which is incorporated herein by reference); (x) an E. coli phosphate binding protein having a A225C, N223C, N226C, S164C, or S39C mutation {e.g., comprising 1, 2, 3, 4, or 5 of these mutations) {see, e.g., U.S. Patent Application Publication No. 2004/0118681 the entire content of which is incorporated herein by reference); or (xi) a Haemophilus influenza (H. influenzae) iron binding protein having a E203C, K202C, K85C, or V287C mutation {e.g., comprising 1, 2, 3, or 4 of these mutations) {see, e.g., U.S. Patent Application Publication No. 2004/0118681 the entire content of which is incorporated herein by reference). In various embodiments, the sample is suspected of comprising urea.

Attorney Docket No. 35327-522001 WO

References and PDB ^a files for bPBP structures, genes, and ligand binding crystal structure bPBP open form closed form DNA sequence ligand affinity arahinose BP Quio ^' chci and Scripture el. a] Clark et al.,

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1GLG

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1DRP

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Various types of samples may be used in methods provided herein. In non-limiting examples, a sample may comprise a reaction product, a buffer, and/or a solvent. In some embodiments, the solvent is an aqueous solvent. In some embodiments, the solvent comprises a non-polar solvent, a polar aprotic solvent, and/or a polar protic solvent. For example, a sample may comprise water, liquid ammonia, liquid sulfur dioxide, sulfuryl chloride, sulfuryl chloride fluoride, phosphoryl chloride, dinitrogen tetroxide, antimony trichloride, bromine pentafluoride, hydrogen fluoride, dimethyl sulfoxide, hexane, benzene, toluene, 1,4-dioxane, chloroform, diethyl ether, dichloromethane, N-methylpyrrolidone, tetrahydrofuran, ethyl acetate, acetone, dimethylfoimamide, acetonitrile, tormic acid, n- butanol, isopropanol, nitromethane, ethanol, methanol, and/or acetic acid.

In embodiments, a sample comprises a Newtonian liquid, a shear thickening liquid, a shear thinning liquid, a thixotropic liquid, a rheopectic liquid, or a Bingham plastic. In some implementations, a sample has a dynamic viscosity of at least about 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, or 2 pascal-seconds (Pa-s) or less than about 2, 1.5, 1.4, 1.3, 1.2, 1.1, 1, 0.9, 0.8, 0.7, 0.6, 0.5 Pa s; and/or a kinematic viscosity of at least about 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, or 2 centistokes (cSt) or less than about 2, 1.5, 1.4, 1.3, 1.2, 1.1, 1, 0.9, 0.8, 0.7, 0.6, 0.5 cSt.

In various embodiments, the sample comprises a biological sample. The sample may comprise, e.g., a clinical sample (i.e., a sample collected in a clinical or veterinary setting, e.g., by or at the request or supervision or direction of a doctor, nurse, aid worker, or medic) and/or a physiological sample (a sample collected from an organism, e.g., a mammal such as a human). In certain embodiments, the biological sample comprises or has been provided or obtained from a skin surface or a mucosal surface. In some embodiments, the biological sample comprises a biological fluid. Non-limiting examples of biological fluids include sweat, tear fluid, blood, serum, plasma, interstitial fluid, amniotic fluid, sputum, gastric lavage, skin oil, milk, fecal matter, emesis, bile, saliva, urine, mucous, semen, lymph, spinal fluid, synovial fluid, a cell lysate, venom, hemolymph, and fluid obtained from plants such as the fluid transported in xylem cells or phloem sieve tube elements of a plant (e.g. sap).

The present subject matter also provides biosensors, methods, compositions, and devices useful for measuring the level of a ligand within a liquid solution or suspension or composition comprising cultured cells or tissue or a supernatant of such a solution or suspension, e.g., a sample of conditioned media or a sample of growth media in which a population of cells was cultured. In some embodiments, the sample is within a culture (e.g., Attorney Docket No. 35327-522001 WO inserted into a bioreactor) or provided from a media, culture, or reaction, e.g., in a bioreactor. For example, the sample may be within or provided from a fermenter such as a culture or culture supernatant from a fermentation reaction (e.g., an ongoing fermentation, such as during beer/wine production, the culture of cells in research settings, the production of a compound, etc.). Thus, the level of a ligand can be assayed at a timepoint of interest or at a series of timepoints over the duration of cell culture, e.g. continuously, in or from a reaction or culture. Bioreactors include devices or systems that support a biologically active environment. For example, a bioreactor may comprise a vessel in which a chemical process is carried out which involves organisms or biochemically active substances derived from such organisms. Such a process can either be aerobic or anaerobic. Organisms growing in bioreactors may be, e.g., submerged or suspended in liquid medium or may be attached to the surface of a solid medium. Submerged cultures may be suspended or immobilized.

Suspension bioreactors can use a wider variety of organisms, since special attachment surfaces are not needed, and can operate at much larger scale than immobilized cultures. However, in a continuously operated process the organisms will be removed from the reactor with the effluent. Immobilization is a general term describing a wide variety of cell or particle attachment or entrapment. It can be applied to basically all types of biocatalysis including enzymes, cellular organelles, and cells (e.g., animal cells, plant cells, fungal cells, and bacterial cells). Immobilization is useful for continuously operated processes, since the organisms will not be removed with the reactor effluent, but is limited in scale because the cells are only present on the surfaces of the vessel. A bioreactor may also refer to a device or system meant to grow cells or tissues in the context of cell culture. The interrogation and/or monitoring of urea levels in such samples permits the evaluation of the status of growth of the cells or production of secreted products by the cells to inform harvest or feeding or other modification of the culture.

Aspects of the present subject matter relate to the use of methods and biosensors provided herein to detect contamination.

In some embodiments, the sample comprises an environmental sample. Depending on context, there are instances in which a biological sample may also be, or may be within, an environmental sample. In certain embodiments, an environmental sample comprises a solute obtained from a biological composition, such as bone, nail, hair, shell, or cartilage. In various embodiments, an environmental sample comprises a solute obtained from an environmental substance and/or an environmental surface. For example, the solute may be Attorney Docket No. 35327-522001 WO dissolved/obtained from the environmental substance and/or an environmental surface using an aqueous or nonaqueous solution. In some embodiments, an aqueous may optionally comprise a nonaqueous solvent (e.g., mixed with an aqueous solvent). Non-limiting examples of environmental substances include rock, soil, clay, sand, meteorites, asteroids, dust, plastic, metal, mineral, fossils, sediment, and wood. Non-limiting examples of environmental surfaces include the surface of a vehicle such as a civilian vehicle (e.g., a satellite, a bike, a rocket, an automobile, a truck, a motorcycle, a yacht, a bus, or a plane) or a military vehicle (e.g., a tank, an armored personnel carrier, a transport truck, a jeep, a mobile artillery unit, a mobile antiaircraft unit, a minesweeper, a Mine-Resistant Ambush Protected (MRAP) vehicle, a lightweight tactical all-terrain vehicle, a high mobility multipurpose wheeled vehicle, a mobile multiple rocket launch system, an amphibious landing vehicle, a ship, a hovercraft, a submarine, a transport plane, a fighter jet, a helicopter, a rocket, or an Unmanned Arial Vehicle), a drone, a robot, a building, furniture, or an organism other than a human. In some embodiments, the sample comprises an environmental fluid. Non-limiting examples of environmental fluids include marine water, well water, drinking well water, water at the bottom of well dug for petroleum extraction or exploration, melted ice water, pond water, aquarium water, pool water, lake water, mud, stream water, river water, brook water, waste water, treated waste water, reservoir water, rain water, and ground water. In some embodiments, waste water comprises sewage water, septic tank water, agricultural runoff, water from an area in which chemical or oil spill has or is suspected of having occurred (e.g., an oil spill into a marine environment), water from an area where a radiation leak has or is suspected of having occurred (e.g., coolant from a nuclear reactor), water within the plumbing of a building, water within or exiting a research facility, and/or water within or exiting a manufacturing facility such as a factory.

As used herein, "suspected" with respect to an event means that there has been at least one test (e.g., a test other than a method or assay provided herein), occurrence (e.g., that is likely to or that may cause the event such as an emergency, leak, accident, flood, earthquake, storm, fire, malfunction, sunk vessel, or crash), or report (e.g., by a witness, informant, or observer) that is consistent with the event having occurred.

In certain embodiments, the sample comprises a food or beverage additive and/or a food or beverage composition. In some embodiments, the food or beverage composition comprises a fermented composition. In various embodiments, the sample comprises a fluid obtained from a food composition. Alternatively or in addition, the sample may comprise a Attorney Docket No. 35327-522001 WO solute dissolved from a food composition. In some examples, a solute is or has been dissolved from a food composition with an aqueous or nonaqueous solution. In various implementations, an aqueous solution may optionally comprise a nonaqueous solvent. In certain embodiments, a sample comprises a food composition in semisolid or liquid form. Non-limiting examples of such compositions include yogurt, soup, ice cream, a broth, a puree, a shake, a smoothie, a batter, a condiment, a sauce, and any combination thereof. In some implementations, a sample is a food engineering process (e.g., obtained from a food design, storage, transport, or production process or from equipment intended to process, transport, or store food). A food composition may comprise, e.g., a plant or a composition isolated from a plant, and/or an animal or a composition isolated from an animal. In various embodiments, a sample comprises a beverage composition. Non-limiting examples of beverage compositions include soft drinks, fountain beverages, water, coffee, tea, milk, dairy- based beverages, soy-based beverages (e.g., soy milk), almond-based beverages (e.g., almond milk), vegetable juice, fruit juice, fruit juice-flavored drinks, energy drinks, sports and fitness drinks, alcoholic products, and beverages comprising any combination thereof. Non-limiting examples of beverage compositions comprising water include purified water (e.g., filtered water, distilled water, or water purified by reverse osmosis), flavored water, mineral water, spring water, sparkling water, tonic water, and any combination thereof. In various embodiments, the sample comprises alcohol. Non-limiting examples of such samples include samples comprising or obtained/provided from beer, malt beverages, liqueur, wine, spirits, and any combination thereof.

Aspects provide methods for detecting, determining, monitoring, or assaying urea levels during the manufacture and/or storage of a food composition. In some embodiments, the level of urea is detected to detect or monitor for food spoilage.

In some embodiments, a sample comprises a nutritional or supplement composition. In certain implementations, the nutritional or supplement composition comprises an omega-3 fatty acid, a vitamin, a mineral, a protein powder, or a meal supplement.

In certain embodiments, a biosensor is implanted in a subject's body. For example, a biosensor may be implanted in a subject's blood vessel, vein, eye, natural or artificial pancreas, alimentary canal, stomach, intestine, esophagus, or skin (e.g., within the skin or under the skin). In various embodiments, the biosensor is configured within or on the surface of a contact lens. In some embodiments, the biosensor is configured to be implanted in or under the skin. In non-limiting examples, the biosensor is implanted in a subject with an Attorney Docket No. 35327-522001 WO optode and/or a microbead. In certain embodiments, the biosensor generates a signal transdermally.

Aspects of the present subject matter provide a method for assaying the level of urea in a subject. The method may comprise contacting a biological sample from the subject with a biosensor for urea under conditions such that the biosensor binds to urea present in the biological sample. The biosensor comprises a reporter group that is attached to a urea- binding protein, and binding of urea to a urea-binding domain of the urea-binding protein causes a change in signaling by the reporter group. In various embodiments, the subject has, is suspected of having, or is undergoing routine testing for reduced kidney function, such as acute kidney injury or chronic kidney disease. In various embodiments, the subject has or is suspected of having, or is undergoing routine testing for a urinary tract obstruction, congestive heart failure or a recent heart attack, gastrointestinal bleeding, dehydration (e.g., resulting from not drinking enough fluids or for other reasons), shock, low blood pressure, a severe burn, toxicity from a medications, such as an antibiotics, or a high-protein diet. In some embodiments, the biological sample comprises blood, plasma, serum, sweat, tear fluid, or urine. In certain embodiments, the biological sample is present in or on the surface of the subject. In various implementations, the biosensor is applied onto or inserted into the subject. For example, the biosensor may be tattooed into the subject or is in or on a device that is implanted into the subject. In some embodiments, the biosensor may be present in or on a contact lens that is worn by the subject. Methods for determining the level of urea, e.g. in a subject who has or is suspected of having a disease or disorder associated with an abnormal urea level, may be performed without other testing related to the disease or disorder, or performed as part of a battery of clinical testing. In some embodiments, the level of urea is determined as part of a kidney function test. In some embodiments, the level of urea is determined to assess and/or monitor kidney function and/or the effectiveness of hemodialysis treatment.

As used herein, "suspected" with respect to a subject's condition (e.g., disease or injury) means that the subject has at least one symptom or test (e.g., a test other than an assay or method provided herein) that is consistent with the condition.

Elevated urea in a bodily fluid (e.g., in the blood) is associated with reduced kidney function.

In various embodiments, the subject has or is suspected of having reduced or impaired kidney function, acute kidney injury, and/or kidney disease (such as chronic kidney disease). Attorney Docket No. 35327-522001 WO

In some embodiments, the biological sample comprises blood, plasma, serum, sweat, tear fluid, or urine. In certain embodiments, the biological sample is present in or on the surface of the subject. In various implementations, the biosensor is applied onto or inserted into the subject. For example, the biosensor may be tattooed into the subject or is in or on a device that is implanted into the subject. In some embodiments, the biosensor may be present in or on a contact lens that is worn by the subject. Methods for determining the level of urea, e.g. in a subject who has or is suspected of kidney dysfunction, may be performed without other testing or as part of a battery of clinical testing. In some embodiments, the method is performed as part of routine testing, e.g., during a doctor visit such as a physical. Thus, the present subject matter provides methods for detecting whether a subject has reduced kidney function. The method may comprise contacting a biological sample from the subject with a biosensor for urea under conditions such that the biosensor binds to urea present in the biological sample. The biosensor comprises a reporter group that is attached to a urea- binding protein, and binding of urea to a urea-binding domain of the urea-binding protein causes a change in signaling by the reporter group.

Any type of abnormal urea level may be assessed, monitored or detected using the compounds, compositions, and methods provided herein. Additionally, any subject who has or is at risk of a disease or injury associated with an abnormal urea level may be assessed and/or monitored using the compounds, compositions, and methods provided herein.

The present subject matter includes a method for monitoring the level of a ligand, comprising periodically or continuously detecting the level of the ligand, wherein detecting the level of the ligand comprises (a) providing or obtaining a sample; (b) contacting the sample with a biosensor for the ligand under conditions such that the ligand-binding protein of the biosensor binds to the ligand, and (c) detecting a signal produced by the biosensor.

Aspects of the present subject matter also provide a method for monitoring the level of a ligand (e.g., urea) in a subject, comprising periodically detecting the level of the ligand in the subject. Detecting the level of the ligand in the subject may comprise (a) providing or obtaining a biological sample from the subject; (b) contacting the biological sample with a biosensor for the ligand provided herein under conditions such that the ligand-binding protein of the biosensor binds to the ligand, if the ligand is present in the biological sample, and (c) detecting (i) a signal produced by a reporter group of the biosensor, or (ii) whether a signal is produced by a reporter group of the biosensor. The level of the ligand may be detected, e.g., Attorney Docket No. 35327-522001 WO at least once every 1, 2, 3, 6, or 12 hours, at least once every 1, 2, 3, or 4 days, at least once every 1, 2, or three weeks, or at least once every 1, 2, 3, 4, 6, or 12 months.

The present subject matter also provides a method for monitoring the level of a ligand in a subject. The method comprises (a) administering a biosensor provided herein or a device comprising a biosensor provided herein to the subject, wherein after administration the biosensor is in contact with a bodily fluid or surface that typically comprises the ligand, and (b) detecting (i) a signal produced by a reporter group of the biosensor continuously or repeatedly at intervals less than about 30 minutes (m), 15m, 10m, 5m, lm, 30 seconds (s), 15s, 10s, 5s, Is, 0.1s, 0.001s, 0.0001s, or 0.00001 apart, and/or (ii) whether a signal is produced by a reporter group of the biosensor continuously or repeatedly at intervals less than about 30m, 15m, 10m, 5m, lm, 30s, 15s, 10s, 5s, Is, 0.1s, 0.001s, 0.0001s, or 0.00001 apart.

Non-limiting aspects of continuously monitoring ligand levels are described in Weidemaier et al. (2011) Biosensors and Bioelectronics 26, 4117-4123 and Judge et al.

(2011) Diabetes Technology & Therapeutics, 13(3):309-317, the entire contents of each of which are hereby incorporated herein by reference.

Also within various implementations is a composition comprising a purified urea- binding fluorescently-responsive sensor protein and a solid substrate, e.g., a particle, a bead such as a magnetic bead, or a planar surface such as a chip or slide, wherein the sensor protein is immobilized onto the solid substrate. In some embodiments, the biosensor is immobilized on a patch. In some embodiments, the patch comprises a polymer or copolymer comprising hydroxyethyl (meth)acrylate, a polyolefin, polyurethane, polystyrene, an ethylene/methacrylic acid copolymer, an ethylene/methyl methacrylate copolymer, a polyester, and/or a polyurethane. In some embodiments, the patch comprises a woven fabric, a knitted fabric, or a nonwoven fabric of a synthetic fiber and/or natural fiber. In certain embodiments, the patch has an adhesive layer. An exemplary solid substrate solid substrate comprises a cyclic olefin copolymer. In some embodiments, the urea-binding protein is thermostable.

A thermostable urea sensor protein is one in which the activity (urea binding) is retained after exposure to relatively high temperatures. For example, the urea sensor protein comprises a mid-point thermal melt transition greater than 30°C, greater than 40°C, greater than 50°C, greater than 60°C, greater than 70°C, greater than 80°C, greater than 90°C, or greater than 100°C, or about 30°C to about 100°C, about 40°C to about 100°C, about 50°C to about 100°C, about 60°C to about 100°C, about 70°C to about 100°C, about 80°C to about Attorney Docket No. 35327-522001 WO

100°C, or about 90°C to about 100°C. In some embodiments, the sensor protein contains a single cysteine residue. In some embodiments, the single cysteine residue is located in a site of the ligand-binding protein, where it responds to ligand binding. In some examples, the protein comprises the amino acid sequence of SEQ ID NO: 32 (csUBP7_95C) or 98

(csUBP7_186C.20), and in some examples, a single cysteine is conjugated to Badan, Acrylodan, or a derivative thereof. For example, the derivative comprises a replacement of the two-ring naphthalene of Acrylodan or Badan with a three-ring anthracene, a fluorene, or a styrene. In other non-limiting examples, a single cysteine is conjugated to Alexa532. A reporter group is covalently bound to the single cysteine. In some situations, the solid substrate comprises a plurality of sensor proteins, each of which comprises a different dissociation constant (KJ) for urea, e.g., for detecting and quantifying urea levels across many ranges of concentrations.

The present subject matter also includes a composition comprising purified urea sensor protein with less than 65% identity and greater than 27% identity (e.g., 44-48% sequence identity) to any one of SEQ ID NOS: 1-22 or 212-222, wherein the sensor protein comprises a single cysteine residue, such that the sensor protein is immobilized onto the solid substrate. As described above, a reporter group is covalently bound to the single cysteine. In some example, the solid substrate comprises a plurality of sensor proteins, each of which comprises a different dissociation constant (Kd) for urea for sensing over a wide range or ranges of urea concentrations.

In some embodiments, a method of detecting the presence of or the quantity of urea in a test sample is carried out using the following steps: contacting the test sample with the biosensor or sensor protein/solid support construct to yield a complex of urea and the ligand- binding protein or biosensor protein; contacting the complex with an excitation light;

measuring an emission intensity of the reporter group from at least two wavelengths;

computing a ratiometric signal from the two (or more) wavelengths; and comparing the signal to a known urea binding curve of signals to identify the presence of or calculate the quantity of urea in the test sample. The test sample may be obtained from a variety of sources. For example, the test sample may be selected from a bodily fluid, a food, a beverage, or a bioreactor culture broth. The testing method may be carried out in vivo, e.g., using an implantable device or dermal patch, or ex vivo.

In various embodiments, the subject to be tested is a mammal, e.g., a primate (such as a human, a monkey, a chimpanzee, or a gorilla), a fish, a bird, a reptile, an amphibian, or an Attorney Docket No. 35327-522001 WO arthropod. In some embodiments, the subject is a fish, a cow, a pig, a camel, a llama, a horse, a race horse, a work horse, a goat, a rabbit, a sheep, a hamster, a guinea pig, a cat, a wolf, a dog (e.g., a pet dog, a work dog, a police dog, or a military dog), a rat, a mouse, a seal, a whale, a manatee, a lizard, a snake, a chicken, a goose, a swan, a duck, or a penguin.

Exemplary Devices and Compositions Comprising Biosensors

Aspects of the present subject matter provide a device comprising one or more biosensors provided herein. Such devices may be, e.g., wearable, implantable, portable, or fixed.

In some embodiments, the device is a nanoparticle or a microparticle comprising the biosensor. Non-limiting examples of devices include devices comprising a test strip, patch, plate, bead, or chip comprising a biosensor provided herein. In certain embodiments, a device may comprise a desiccated biosensor.

The present subject matter also provides a contact lens or a skin patch comprising a biosensor provided herein. In some embodiments, the biosensor is throughout the contact lens or skin patch or within a particular region or zone of a contact lens or skin patch (e.g., in one or more shapes (e.g., a square, circle, or star), dots, lines, or zones, located at the periphery or a portion of the periphery of a contact lens or patch). In some embodiments, the skin patch comprises an adhesive that facilitates attachment of the patch to the surface of skin.

Devices provided herein may include a variety of structural compositions. For example, many polymers (including copolymers), and plastics may be used. Non-limiting examples of compositions useful in certain devices include glass, polystyrene, polypropylene, cyclic olefin copolymers, ethylene-norbornene copolymers, polyethylene, dextran, nylon, amylase, paper, a natural cellulose, a modified cellulose, a polyacrylamide, gabbros, gold, and magnetite (as well as combinations thereof). In some embodiments, the device comprises a hydrogel, a cryogel, or a soluble gel. For example, the biosensor may be incorporated into or onto the hydrogel, cryogel, or soluble gel. In various embodiments, the device comprises a matrix comprising nanopores, micropores, and/or macropores. In certain embodiments, the surface of a device comprises a polymer. In an embodiment, the surface comprises the surface of a particle or a bead having a diameter of about 0.001-1, 0.001-0.1, 0.01-0.1, 0.001-0.01, 0.1-1, 0.1-0.5, or 0.01-0.5 centimeters (cm). For example, the particle comprises a nanoparticle or a microparticle. Attorney Docket No. 35327-522001 WO

Non-limiting examples of polymers include cyclic olefin copolymers, ethylene- norbornene copolymers, polylactic acid, polyglycolic acid, agarose, alginate, poly(lactide-co- glycolide), gelatin, collagen, agarose, natural and synthetic polysaccharides, polyamino acids, poly(lysine), polyesters, polyhydroxybutyrates, polyanhydrides, polyphosphazines, polyvinyl alcohol, polyalkylene oxide, polyethylene oxide, polyallylamines, polyacrylates, modified styrene polymers, poly(4-aminomethylstyrene), pluronic polyols, polyoxamers, polyuronic acid, polyvinylpyrrolidone, hydroxyethyl (meth)acrylate, polyolefins, polyurethane, polystyrene, ethylene/methacrylic acid copolymers, ethylene/methyl methacrylate copolymers, polyester, and polyurethane. In some embodiments, the patch comprises a woven fabric, a knitted fabric, or a nonwoven fabric of a synthetic fiber and/or natural fiber.

Non-limiting examples of temporary tattoo compositions for application to a subject's skin are discussed in U.S. Patent Application Publication No. 20090325221, published December 31, 2009, and U.S. Patent No. 6,428,797, the entire conents of each of which are incorporated herein by reference. Biosensor disclosed herein may be incorporated into any temporary tattoo or other composition for application to the skin. For example, a temporary tattoo decal for application to a subject's skin and configured to detect the presence of a ligand may comprise, e.g., a base paper or plastic; a water-soluble slip layer applied to the base paper or plastic; a temporary tattoo applied to the water-soluble release layer on the base paper, wherein the temporary tattoo comprises a biosensor disclosed herein; an adhesive layer overlying the temporary tattoo; and a protective sheet overlying the adhesive layer.

In some embodiments, the device comprises a plastic polymer comprising cyclic olefin copolymer (COC), such as e.g. TOP AS® COC. Several types of cyclic olefin copolymers are available based on different types of cyclic monomers and polymerization methods. Cyclic olefin copolymers are produced by chain copolymerization of cyclic monomers such as 8,9,10-trinorborn-2-ene (norbornene) or 1, 2,3,4 ,4a,5,8,8a-octahydro- l,4:5,8-dimethanonaphthalene (tetracyclododecene) with ethene (such as TOP AS Advanced Polymer's TOP AS, Mitsui Chemical's APEL), or by ring-opening metathesis polymerization of various cyclic monomers followed by hydrogenation (Japan Synthetic Rubber's ARTON, Zeon Chemical's Zeonex and Zeonor). See, e.g., International Union of Pure and Applied Chemistry (2005) Purr. Appl. Chem. 77(5):801-814. These later materials using a single type of monomer may be referred to as cyclic olefin polymers (COPs). A CAS Registry number for COC is 26007-43-2. Attorney Docket No. 35327-522001 WO

In some embodiments, the biosensor is covalently or noncovalently (e.g.,

electrostatically) attached to a surface of a device. In certain embodiments, the biosensor is attached to a surface of a device or is not attached to a surface of the device (e.g., the biosensor is physically present within the device as a component of a solution or powder but not chemically immobilized onto or into a device surface). For example, the biosensor may move within the confines of a device chamber.

A biosensor may be attached to a device via a variety or means, e.g., via attachment motif. In some embodiments, the attachment motif is attached to the N-teiminus or the C- terminus of the biosensor. In certain embodiments, the biosensor is linked to an attachment motif via a covalent bond. In various embodiments, the biosensor is linked to the attachment motif via a linker. A non-limiting example of a linker is a polyglycine comprising 2, 3, 4, 5, or more glycines and optionally further comprising a serine. In some embodiments, the attachment motif comprises a polypeptide. Non-limiting examples of polypeptides useful in attachment moieties include hexahistidine peptides, hexalysine peptides, zinc-finger domains (ZF-QNKs), and disulfide-containing truncated zinc fingers (pZifs). An example of a hexalysine peptide comprises amino acids in the sequence of SEQ ID NO: 108, an example of a ZF-QNK comprises amino acids in the sequence of SEQ ID NO: 106, and an example of a βΖίί comprises amino acids in the sequence of SEQ ID NO: 105. In some embodiments, the attachment motif comprises a polypeptide that binds to plastic or cellulose.

The hexahistidine, hexalysine, βΖίί and QNK-ZF fusions enable FRSs to be immobilized onto chemically functionalized surfaces. Non-limiting aspects of chemically functionalized surfaces are discussed in Biju, V., 2014, Chem Soc Rev, 43, 744-64 and McDonagh, 2008, Chem Rev, 108, 400-422, the entire contents of which are incorporated herein by reference. Directed evolution methods have been used to develop peptides that bind directly to non-functionalized surfaces (Care, Bergquist and Sunna, 2015, Trends Biotechnol, 33, 259-68; Baneyx, 2007, Curr. Opin. Biotechnol, 18, 312-317; Gunay and Klok, 2015, Bioconjug Chem, 26, 2002-15), including various plastics (Adey et al., 1995, Gene, 156, 27-31; Serizawa et al., 2005, J Am Chem Soc, 127, 13780-1; Serizawa, Sawada and Kitayama, 2007a, Angew Chem IntEd Engl, 46, 723-6; Serizawa, Sawada and Matsuno, 2007b, Langmuir, 23, 11127-33; Serizawa, Techawanitchai and Matsuno, 2007c,

Chembiochem, 8, 989-93; Matsuno et al., 2008, Langmuir, 24, 6399-403; Chen, Serizawa and Komiyama, 2011, JPept Sci, 17, 163-8; Kumada, 2010, J. Biosci. and BioEng., 109, 583- 587; Date et al., 2011, ACS Appl Mater Interfaces, 3, 351-9; Vodnik, Strukelj and Lunder, Attorney Docket No. 35327-522001 WO

2012, J. Biotech., 160, 222-228; Kumada, 2014, Biochem. etBiophys. Acta, 1844, 1960- 1969; Ejima, Matsuno and Serizawa, 2010, Langmuir, 26, 17278-85), inorganic

materials(Hnilova, 2012, Soft Matter, 8, 4327-4334; Care et al., 2015, Trends Biotechnol, 33, 259-68), nanoparticles (Awakumova et al., 2014, Trends Biotechnol, 32, 11-20), and cellulosic paper (Guo et al., 2013, Biomacromolecules, 14, 1795-805). Such peptides, or natural material-binding domains (Oliveira et al., 2015, Biotechnol Adv, 33, 358-69), also can be fused to FRSs to direct site-specific, oriented immobilization on their target materials while preserving FRS function. For instance, plastic-binding peptides have been developed that direct immobilization on polystyrene (Adey et al., 1995, Gene, 156, 27-31 ; Serizawa et al., 2007c, Chembiochem, 8, 989-93; Kumada, 2010, Biochem. etBiophys. Acta, 1844, 1960- 1969; Vodnik et al., 2012, Anal Biochem, 424, 83-6), polymethyl acrylate (Serizawa et al., 2005, J Am Chem Soc, 127, 13780-1 ; Serizawa et al., 2007a, Angew Chem IntEdEngl, 46, 723-6; Serizawa et al., 2007b, Langmuir, 23, 11127-33; Kumada, 2014, Biochem. etBiophys. Acta, 1844, 1960-1969), polycarbonate (Kumada, 2012, J. Biotech., 160, 222-228), polylactide (Matsuno et al., 2008, Langmuir, 24, 6399-403), and polyphenylene vinylene (Ejima et al., 2010, Langmuir, 26, 17278-85). Cellulose-binding peptides (Guo et al., 2013, Biomacromolecules, 14, 1795-805) and natural domains (Oliveira et al., 2015, Biotechnol Adv, 33, 358-69; Shoseyov, Shani and Levy, 2006, Microbiol Mol Biol Rev, 70, 283-95) can be used to immobilize fusion proteins on paper. Inorganic material include noble metals (Hnilova, 2012, Soft Matter, 8, 4327-4334), semi-conductors (Care et al., 2015, Trends Biotechnol, 33, 259-68), and fluorescent quantum dots(Medintz et al., 2005, Nat Mater, 4, 435-46; Lee et al., 2002, Science, 296, 892-5). The entire contents of each of the references above (and all other references herein) is incorporated herein by reference.

In some embodiments, the attachment motif is attached to a device surface and/or within a matrix of the device. In some embodiments, a biosensor is attached to an attachment motif via a covalent bond and the attachment motif is attached to a device via a covalent bond. Non-limiting examples of covalent bonds include disulfide bonds, ester bonds, thioester bonds, amide bonds, and bonds that have been formed by click reactions. Non- limiting examples of a click reaction include a reaction between an azide and an alkyne; an azide and an alkyne in the presence of Cu(I); an azide and a strained cyclooctyne; an azide and a dibenzylcyclooctyne, a difiuorooctyne, or a biarylazacyclooctynone; a diaryl-strained- cyclooctyne and a 1,3-nitrone; an azide, a tetrazine, or a tetrazole and a strained alkene; an azide, a tetrazine, or a tretrazole and a oxanorbornadiene, a cyclooctene, or a trans- Attorney Docket No. 35327-522001 WO cycloalkene; a tetrazole and an alkene; or a tetrazole with an amino or styryl group that is activated by ultraviolet light and an alkene.

Alternatively or in addition, a surface of a device may be modified to contain a moiety (e.g. a reactive group) what facilitates the attachment of a biosensor and/or binds to the biosensor. In some embodiments, the biosensor is attached to a surface via a biotin-avidin interaction.

In various implementations, the device comprises a first region or chamber for receiving a sample and a second region or chamber that comprises the biosensor, wherein the first region or chamber is separated from the second region or chamber by a filter. In some examples, the filter is impermeable to compounds greater than about 1, 2, 3, 4, 5, 10, 50, 200, or 250 kiloDalton (kDa) in size. The sample may comprise, e.g., a tube, such as a tube that is configured for centrifugation. When sample is placed into the first region and the device is centrifuged, then a portion of the sample comprising a ligand flows through the filter into the second region where the biosensor is contacted.

Non-limiting examples of devices provided herein include endoscopy probes and colonoscopy probes.

In some embodiments, the device comprises an optode. In non-limiting examples, the optode comprises an optical fiber and a single biosensor or composite biosensor. In certain embodiments, the single biosensor or composite biosensor is immobilized on the surface or at an end of the optical fiber. In some embodiments, the optode is configured for implantation into a subject. Alternatively or in addition, the optode is configured for insertion into a sample.

The devices provided herein may optionally comprise a biosensor panel, a composite sensor, a sensor array, and/or a composition comprising a plurality of biosensors. In various embodiments, a device comprises multiple urea biosensors that detect a range of different urea concentrations in a single sample and/or assay run (i.e., each biosensor has a different affinity for urea). Devices may provide spatial localization of multiple biosensors to provide the necessary addressability of different elements in a multi-sensor array comprising sensors that differ in their engineered affinities for coverage of a wide range of urea concentrations, or sensors that each detects distinct analytes.

Aspects of the present subject matter provide a biosensor panel comprising a plurality of biosensors, wherein the plurality of biosensors comprises at least one biosensor disclosed Attorney Docket No. 35327-522001 WO herein. In some embodiments, the plurality comprises at least about 2, 3, 4, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 biosensors.

The present subject matter also provides a composite sensor. The composite sensor may comprise a sensor element, wherein the sensor element comprises 2 or more biosensors, wherein at least 1 of the 2 or more biosensors is a biosensor disclosed herein. In some embodiments, the biosensors are not spatially separated in the sensor element, e.g., the biosensors are mixed within a solution, or immobilized on a surface of the sensor element. Alternatively, a mixture of different biosensors is physically present, e.g., loose, within a region or chamber of a sensor device/structure. In various embodiments, the composite sensor comprises a plurality of sensor elements, wherein each sensor element of the plurality of sensor elements comprises 2 or more biosensors, wherein at least 1 of the 2 or more biosensors is a biosensor provided herein. In some embodiments, the plurality of sensor elements comprises at least about 2, 3, 4, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 sensor elements.

Also included herein is a sensor array comprising a plurality of biosensors of the present subject matter. The sensor array may include, e.g., multichannel array or a multiplexed array. In some embodiments, the biosensors of the plurality of biosensors are spatially separated from each other. In certain embodiments, the biosensors are arranged linearly or in a grid on a surface of the array.

The present subject matter provides a composition comprising a plurality of biosensors including at least one biosensor disclosed herein. Also provided is a non-human mammal comprising a biosensor or device disclosed herein.

Exemplary Polypeptides and Polynucleotides

The present subject matter provides polynucleotides encoding any one of the polypeptides disclosed herein. The polypeptides are also provided. In various embodiments, the polynucleotides are codon-optimized for expression in a desired host cell, such as bacterial cells (e.g., E. coli), yeast, insect cells, plant cells, algal cells, or mammalian cells. The polypeptides provided herein include polypeptides comprising the amino acid sequence of any one of SEQ ID NOS: 1-104 or 212-222. The polynucleotides provided herein include polynucleotides encoding a polypeptide comprising the amino acid sequence of any one of SEQ ID NOS: 1-104 or 212-222. Attorney Docket No. 35327-522001 WO

The polypeptides and biosensors provided herein may be in a variety of forms, e.g., purified in solution, dried (e.g. lyophilized) such as in the form of a powder, and in the form of a crystal (e.g., a crystal suitable for x-ray crystallography). Thus, aspects of the present subject matter provide crystal structures and crystalized forms of the ligand-binding proteins and biosensors disclosed herein. Such crystal structures and crystalized proteins are useful for designing and optimizing biosensors using principles and methods discussed herein.

Also provided are expression vectors comprising a polynucleotide of the present subject matter and/or encoding a polypeptide disclosed herein. Non-limiting examples of expression vectors include viral vectors and plasmid vectors. In some embodiments, an expression vector comprises nucleotides in the sequence set forth as any one of SEQ ID NOS: 109-201. In various embodiments, a polynucleotide encoding a ligand-binding protein and/or biosensor is operably linked to a promoter. The promoter may be expressed, e.g., in a prokaryotic and/or a eukaryotic cell.

The subject matter further includes an isolated cell comprising an expression vector provided herein. The isolated cell may be, e.g., a bacterial cell, a yeast cell, an algal cell, a plant cell, an insect cell, or a mammalian cell. Also included is a non-human multicellular organism such as a plant or an animal (e.g., an insect, a mammal, a worm, a fish, a bird, or a reptile) comprising an expression vector disclosed herein.

Exemplary Methods for Designing Biosensors

Aspects of the present subject matter provide method of identifying a candidate ligand-binding protein for use in a biosensor, comprising: (a) selecting a first protein having a known amino acid sequence (seed sequence), wherein the first protein is known to bind urea; (b) identifying a second protein having an amino acid sequence (hit sequence) with at least 15% sequence identity to the seed sequence; (c) aligning the seed amino acid sequence and the hit sequence, and comparing the hit sequence with the seed sequence at positions of the seed sequence that correspond to at least 5 primary complementary surface (PCS) amino acids, wherein each of the at least 5 PCS amino acids has a hydrogen bond interaction or a van der Waals interaction with urea when urea is bound to the first protein; and (d) identifying the second protein to be a candidate ligand-binding protein if the hit sequence comprises at least 5 amino acids that are consistent with the PCS.

The present subject matter also includes a method for constructing a candidate biosensor, comprising: (a) providing a candidate ligand-binding protein; (b) generating a Attorney Docket No. 35327-522001 WO structure of the second protein; (c) identifying at least one putative allosteric, endosteric, or peristeric site of the second protein based on the structure; (d) mutating the second protein to substitute an amino acid at the at least one putative allosteric, endosteric, or peristeric site of the second protein with a cysteine; and (e) conjugating a fluorescent compound to the cysteine. In some embodiments, the structure comprises a homology model of the second protein generated using a structure of the first protein. In some embodiments, the structure comprises a structure experimentally determined by nuclear magnetic resonance spectroscopy or X-ray crystallography.

Aspects of the present subject matter further provide a method for constructing a biosensor comprising a desired dissociation constant (Kd) for urea, comprising: (a) providing an initial biosensor that does not comprise the desired Kd for urea, wherein the initial biosensor is a biosensor provided herein; (b) mutating the initial biosensor to (i) alter a direct interaction in the PCS between the initial biosensor and bound urea; (ii) manipulate the equilibrium between open and closed states of the initial biosensor; (iii) alter an interaction between the ligand-binding protein and the reporter group of the initial biosensor; or (iv) alter an indirect interaction that alters the geometry of the binding site of the biosensor, to produce a modified biosensor; and (c) selecting the modified biosensor if the modified biosensor comprises the desired Kd for urea. In some embodiments, the reporter group comprises Acrylodan, Badan, or a derivative thereof, and mutating the initial biosensor in (b) comprises altering an interaction between the ligand-binding protein and a carbonyl group of the Acrylodan, Badan, or derivative thereof. In some embodiments, the reporter group comprises Acrylodan, Badan, or a derivative thereof, and mutating the initial biosensor in (b) comprises altering an interaction between the ligand-binding protein and a naphthalene ring of the Acrylodan, Badan, or derivative thereof. In some embodiments, the reporter group comprises Acrylodan, Badan, or a derivative thereof, wherein the Acrylodan, Badan, or derivative thereof is attached to the amino acid of the urea-binding protein that aligns with position 26, 27, 30, 69, 90, 91, 95, 116, 157, 186, or 211 of csUBP7 (SEQ ID NO: 18 or 218) when the amino acid sequence of the urea-binding protein is aligned with the amino acid sequence of csUBP7 using the ClustalW alignment program. In certain embodiments, the reporter group comprises Alexa 532, and mutating the initial biosensor in (b) comprises altering an interaction between the urea-binding protein and the Alexa 532. In some embodiments, the reporter group comprises Alexa 532, wherein the Alexa 532 is attached to the amino acid of the urea-binding protein that aligns with position 26, 27, 30, 69, 90, 91, 95, 116, 157, 186, or Attorney Docket No. 35327-522001 WO

211 of csUBP7 (SEQ ID NO: 18 or 218) when the amino acid sequence of the urea-binding protein is aligned with the amino acid sequence of csUBP7 using the ClustalW alignment program.

In some embodiments, mutating the initial biosensor comprises introducing a substitution mutation into the initial biosensor. In some embodiments, the method further comprises immobilizing the affinity-tuned biosensor on a substrate.

In some embodiments, the second protein comprises (i) amino acids in the sequence of any one of SEQ ID NOS: 1-104 or 212-222; (ii) a stretch of amino acids in a sequence that is least about 95, 96, 97, 98, or 99% identical to the sequence of any one of SEQ ID NOS: 1- 104 or 212-222; (iii) a stretch of at least about 50, 100, 150, 200, 250, 300, 350, or 400 amino acids in a sequence that is at least about 95, 96, 97, 98, or 99% identical to a sequence within any one of SEQ ID NOS: 1-104 or 212-222; or (iv) a stretch of at least about 50, 100, 150, 200, 250, 300, 350, or 400 amino acids in a sequence that is identical to a sequence within any one of SEQ ID NOS: 1-104 or 212-222. In various embodiments, attaching the reporter group to the putative allosteric, endosteric, or peristeric site of the first protein comprises substituting a cysteine at the site with a cysteine. For example, the reporter group is conjugated to the cysteine. Preferably, attaching a reporter group to the corresponding amino acid of the second protein produces a functional biosensor.

The selected first protein (e.g., the amino acid sequence thereof) may be novel or known. However, in many instances, the function of the first protein will not be known. In a non-limiting example, identifying a protein not previously known to have urea binding activity may comprise a structurally assisted functional evaluation (SAFE) homolog search method comprising the following steps:

(1) Collecting a sequence homology set using a BLAST sequence alignment tool starting with a urea-binding protein or a homologue thereof (paAmiC, avUBP, cgUBP, mpUBPl, mhUBP2, bsUBP3, dcUBP4, gtUBP5, ctUBP6, csUBP7, taUBP8, gkUBPIO, psUBPl 1, or teUBP12) sequence disclosed herein as a seed. Permissive settings are used, such that pairwise hits are required to have a minimum of only, e.g., 20%, 25%, 30%, 35% or 40% sequence identity with the seed sequence. The lengths of the hit and seed are mutually constrained such that the alignment covers at least, e.g., 60%, 65%, 70%, 85%, or 90% within each partner.

(2) Structure-based encoding of biological function: A primary complementary surface (PCS) comprising the protein residues that form hydrogen bonds and van der Waals Attorney Docket No. 35327-522001 WO contacts with a bound urea is defined using computer-assisted, visual inspection of the three- dimensional structure of the protein-urea complex. This definition specifies residue positions and their permitted amino acid identity. Multiple amino acid identities are permitted at each position to encode functionally equivalent residues. This definition establishes a search filter for the accurate prediction of urea-binding proteins within the universe of sequence homologs collected in (1). For example, a candidate's residue corresponding to position 85 of paAmiC may be S or T, a candidate's residue corresponding to position 104 of paAmiC may be W, Y, or T, a candidate's residue corresponding to position 106 of paAmiC may be T, I, Q, V, or S, a candidate's residue corresponding to position 107 of paAmiC may be P, Q, E, F, L, Y, C, or W, a candidate's residue corresponding to position 150 of paAmiC may be Y, a candidate's residue corresponding to position 152 of paAmiC may be Y, F, V, or W, a candidate's residue corresponding to position 206 of paAmiC may be V, N, G, or L, and/or a candidate's residue corresponding to position 233 of paAmiC may be T, S, E, M, A, or C.

(3) Accurate sequence alignment: Tools such as ClustalW are used to construct an accurate alignment of all the sequence homologs. The seed sequence is included in the alignment. This multiple sequence alignment establishes the equivalent positions of the seed urea-binding protein (primary complementary surface) PCS in each sequence homolog.

(4) Function evaluation: The urea-binding properties of each of the aligned sequence homologs is determined by measuring their compliance with the PCS sequence filter. A "Hamming distance", H, is assigned for each homolog, which specifies the degree of sequence identity of all the residues at the aligned PCS positions. A value of H=0 indicates that the identities of all the residues at the aligned PCS positions match the amino acid(s) allowed in the PCS search filter; H>0, indicates that one or more aligned positions have disallowed residues. Sequences for which H=0 are predicted to encode urea-binding proteins.

(5) Selection of representative SAFE homologs: The sequence homologs are ordered by (a) identity with the seed PCS, as measured by the Hamming distance, (b) fractional overall sequence identity with the seed sequence. A subset for sequences with H=0, sampling the fractional overall sequence identity is selected for experimental verification.

In a non-limiting example, identifying a protein not previously known to have urea binding activity may comprise the following steps:

(1) performing a computational search of sequence databases to define a broad group of simple sequence or structural homologs of any known, urea-binding protein; Attorney Docket No. 35327-522001 WO

(2) using the list from step (1), deriving a search profile containing common sequence and/or structural motifs shared by the members of the list [e.g. by using computer programs such as MEME (Multiple Em for Motif Elicitation available at

meme.sdsc.edu/meme/cgi-bin/meme.cgi) or BLAST];

(3) searching sequence/structural databases, using a derived search profile based on the common sequence or structural motif from step (2) as query (e.g., using computer programs such as BLAST, or MAST (Motif Alignment Search Tool available at

meme.sdsc.edu/meme/cgi-bin/mast.cgi), and identifying a candidate sequence, wherein a sequence homology and/or structural similarity to a reference urea-binding protein is a predetermined percentage threshold;

(4) compiling a list of candidate sequences to generate a list of candidate urea- binding proteins;

(5) expressing the candidate urea-binding proteins in a host organism; and

(6) testing for urea binding activity, wherein detection of urea binding in the organism (or the media thereof) indicates that the candidate sequence comprises a novel urea binding protein.

In non-limiting examples, the MEME suite of sequence analysis tools

(meme.sdsc.edu/meme/cgi-bin/meme.cgi) can also be used as an alternative to BLAST. Sequence motifs are discovered using the program "MEME". These motifs can then be used to search sequence databases using the program "MAST." The BLAST search algorithm is well-known.

In various embodiments relating to alignments using a ClustalW aligment program, the ClustalW alignment program may be, e.g., ClustalW alignment program version 2.1.

Each embodiment disclosed herein is contemplated as being applicable to each of the other disclosed embodiments. Thus, all combinations of the various elements described herein are within the scope of the invention.

Other features and advantages of the invention will be apparent from the following description of the preferred embodiments thereof, and from the claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. Attorney Docket No. 35327-522001 WO

DESCRIPTION OF THE DRAWINGS

FIG. 1 A is a cartoon and FIGS. 1B-D are graphs illustrating fluorescently responsive sensors. FIG. 1 A: FRSs can be constructed by site-specifically attaching a fluorophore to a protein that undergoes a conformational change upon binding ligand (triangle) in a location between the two lobes of the protein (periplasmic binding protein or engineered derivative thereof), such that the shape and intensities of the fluorescent conjugate emission spectra changes. FIG. IB: In the absence of ligand, the emitted fluorescence color is predominantly blue, whereas the ligand complex fluoresces green. Arrows indicate the direction of change upon ligand addition. FIG. 1C: The ligand dependence of the absolute blue and green intensities. FIG. ID: The ratio of the blue and green emission intensities enables ligand binding to be determined.

FIGS. 2A and B show the structures of area (FIG. 2A) and acetamide (FIG. 2B).

FIG. 3 is an illustration showing that residues that contact acetamide comprise the primary complementary surface in paAmiC [Protein Data Bank (PDB) accession code: lpea]. T106 has been omitted for clarity; it forms van der Waals contacts with the acetamide plane facing the viewer.

FIGS. 4A-B are a diagrams showing linkage relationships in the Anabaena variabilis and Corynebacterium glutamicum urea uptake operons. a. A. variabilis (genome

NC_007413). Genes: urtA, YP_324854.1; urtB, YP_324855.1; urtC, YP_324856.1; uriD, YP 3248557.1; uriE, YP 324858.1. b. C. glutamicum (genome NC 022040). Genes: urtA, YP_008401061.1; urtB, YP_008401062.1; urtC, YP_008401063.1; urtD, YP_008401064.1; uriE, YP 008401065.1. Each tick mark of the rulers of FIGS. 4A and 4B shows 1 kb of spacing. Figure generated with 'Genome Viewer'.

FIGS. 5A-C are graphs showing SAFE homology search statistics. FIG. 5A: Binned distribution of identity scores of hits using the paAmiC sequence as the search seed f, the normalized count of sequences within a frequency score bin). Solid line: all sequences; broken line: the subset of sequences that match the urea-binding PCS (Hamming score, H=0). Note that the predicted urea-binding proteins tend to be distant homologs of paAmiC. FIG. 5B: Identity score distribution using the csUBP7 sequence as the search seed. Note that the subset of urea-binding proteins tends to be fairly closely related to the seed. FIG. 5C:

Distribution of Hamming scores, H, within the set of csUBP7 homologs (N is the count with Attorney Docket No. 35327-522001 WO a particular Hvalue). Note that (i) the majority of sequences are not urea-binding proteins (i.e. H>0), and (ii) the paucity of closely related PCS sequences (H=[l,2]).

FIG. 6 is an alignment of the selected lead sequences (see Table 4 for naming).

Location of secondary structure elements is indicated. Leader peptides are indicated in grey. Dark grey indicates the sequence that was deleted in the mature protein expression constructs (note that for mpUBPl and mhUBP2, this deletion extends two residues beyond the predicted boundary between the leader peptide and mature protein). Endogenous cysteines are shown (if present).

FIGS. 7A-C are structures and structural aspects of csUBP7 determined by X-ray crystallography. FIG. 7A: Structural alignment of csUBP7 and paAmiC. Urea is indicated. FIG. 7B: Primary complementary surface of csUBP7 (cf. FIG. 3). VI 13 has been omitted for clarity; it forms van der Waals contacts with the urea plane facing the viewer. FIG. 7C Sites of cysteine mutations (gray spheres) for covalent attachment of fluorophores.

FIG. 8 is a sequence comparison of the paAmiC and csUBP7 sequence and secondary structure element alignments. Numbering according to paAmiC.

FIG. 9 is an alignment showing the location of cysteine mutations for attachment of thiol-reactive fluorophores in csUBP7, ctUBP6, and bsUBP3. The aligned sequences of the proteins in the expression constructs are shown (sequence numbering according to csUBP7). The locations and structural classes of the cysteine mutations are indicated: e, endosteric; a, allosteric; p, peristeric. Underline indicates a position for which at least one conjugate in one homolog responded to urea binding. The mutations listed in Tables 7 and 8 are outlined in grey.

FIGS. 10A-F are graphs showing temperature- and urea-dependent ratiometric fluorescent landscapes of responsive and non-responsive fluorescent conjugates of csUBP7. Data was collected on a Roche LightCycler real-time PCR instrument, recording emission intensities at 488 nm and 580 nm as a function of temperature and urea concentration. FIGS. lOA-C correspond to csUBP7 186C Acrylodan that responds to urea binding and exhibits thermal denaturation (r _m =364 K), FIGS. 10 D-F: csUBP7 158C Acrylodan exhibits a thermal denaturation transition (r _m =360 K), but does not report on urea binding. First row, temperature melts of 12 different urea concentrations. FIG. 10A inset shows the isothermal urea-binding curve for the responsive conjugate csUBP7 186C Acrylodan, with a of 0.4 mM at 298 K (25 °C). Second and third row; three-dimensional landscapes representing the ratio of fluorescence emission intensities (Z axis) at 488 nm and 580 nm as a function of Attorney Docket No. 35327-522001 WO temperature and urea concentration. Indicated are the main equilibrium states: N, native apoprotein; D, denatured protein; S, saturated urea complex.

FIGS. 11 A-C are graphs showing that csUBP7 95C Badan conjugate exhibits a dichromatic response to urea. FIG. 11 A: Emission spectra. Purple, no urea; red, saturating urea; black, intermediate urea concentrations; arrows, change in intensity with increased urea concentration. FIG. 1 IB: Dichromatic signal (λι= 479 nm, λ ₂ = 510 nm; black circles, experimental data points; gray lines, fit to binding isotherm, ^&V9 K _& = 2.1 mM, see Table 6). FIG. 11C: Monochromatic signal (gray, 479 nm data points and fit; black, 510 nm data points and fit; 2.2 mM).

FIGS. 12A-P are depictions of fluorophore chemical structures. Naphthalene family:A, Acrylodan; B, Badan; C, IAEDANS. Xanthene family: D, Fluorescein (5-IAF and 6-IAF); E, Oregon Green; F, Alexa 432; G, Alexa 532; H, Alexa 546; I, Texas Red.

Coumarin family: J, Pacific Blue; K, CPM. benzoxadiazole family: L, IANBD.

Boradiazaindacine (BODIPY) family: M, BODIPY 499/508; N, BODIPY 507/545. Cyanine family: O, Cy5. Miscellaneous: P, PyMPO.

FIGS. 13A, C, and D are graphs and FIG. 13B is a depiction of a chemical structure, each of which relate to the urea response of the dually labeled csUBP7 Ql 14A

186C Alexa532 βΖίί· Acrylodan conjugates. In this ngmFRET system, Alexa532 is the environmentally responsive acceptor, and Acrylodan the donor. FIG. 13 A: Emission spectra. Purple, no urea; red, saturating urea; black, intermediate urea concentrations; arrows, change in intensity with increased urea concentration. FIG. 13B: Structure of Alexa532. Arrow indicates site possible carbonyl twist. FIG. 13C: Dichromatic signal (λ]= 491 nm, λ ₂ = 555 nm; black circles, experimental data points; gray lines, fit to binding isotherm, ^app .¾ ⁼ 2.0 mM). FIG. 13D: Monochromatic signal (black, 491 nm data points and fit; gray, 555 nm data points and fit; 2.6 mM).

FIG. 14 is a set of cartoons depicting fusion constructs for sensor immobilization. Light gray, csUBP7 186C 114A; diagonal striped, hexa-lysine immobilization tag; dark gray, hexa-histidine affinity purification tag; horizontal striped, ZF-QNK zinc finger domain; vertical striped, truncated zinc finger βΖίί domain; wavy line, Gly-Gly-Ser linker (two segments, indicate Gly-Gly-Ser-Gly-Gly-Ser). Left column, names of constructs.

FIGS. 15A-D are graphs showing that the immobilization of csUBP7 950Badan does not affect its thermostability or its binding affinity to urea. FIG. 15 A: Urea titration curve determined for magnetic Ni-NTA beads coated with immobilized csUBP7 95C-Badan. Attorney Docket No. 35327-522001 WO

Dichromatic signal (λι= 483 nm, λ ₂ = 525 nm); circles, experimental data points; gray lines, fit to binding isotherm, ^app .¾ ⁼ 2.0 mM. FIGS. 15B-D: Thermostability was determined by measuring the ratio fluorescence emission intensities through 488 nm and 510 nm filters as a function of temperature in a Roche LightCycler. FIG. 15B: Solution (r _m =352 K). FIG. 15C: Immobilized on Ni-NTA beads (r _m =352 K). FIG. 15D: Reconstituted, desiccated Ni-NTA beads (r _m =352 K).

FIGS. 16A-D are diagrams showing three dominant factors that affect ngmFRET between donor and acceptors in which one partner responds to ligand binding. FIG. 12A: Simplified Jablonski diagram illustrating radiative and non-radiative pathways in the donor and acceptor. The donor excited state (£>*) is formed through illumination by the excitation source (wavy arrow) whereas the acceptor excited state (A*) is formed by resonance energy transfer (dashed arrow). The fluorescence intensity is determined by the ratio of radiative decay (gray arrows) of the excited states (gray lines) to the ground state (black line) relative to all non-radiative processes (black arrows), and the resonance energy transfer rate, k _t , from donor to acceptor. FIG. 12B: Inter-dipole geometry. Top, FRET efficiency

( / = Q _r /(Q ₀ —Q _∞ ), where the Q„ Qo, Q _∞ are the quantum efficiencies at distances r, closest approach, and infinity, respectively) varies as the 6 ^th power of the distance between two dipoles. Bottom, FRET efficiency varies as the square of the orientation factor κ, where K— sin^ sin#4 cos χ - 2 cos Θ _Ό cos Θ _Α with and ΘΑ the angles of the donor (blue) and acceptor (red) electronic transition dipoles with the line connecting them, and χ the angle between the planes within which they lie. FIG. 12C: Spectral overlap (grey area) between the donor fluorescence emission ( ^D I, blue) and acceptor fluorescence excitation ( A, black) spectra. This overlap increases with bathochromic or hypsochromic shifts of the donor emission (red arrow) and acceptor excitation (dotted blue arrow) spectra, respectively. Shifts in the opposite directions decreases spectral overlap.

FIG. 17 shows the sequence of an exemplary mpUBPl expression construct (SEQ ID NO: 109).

FIG. 18 shows the sequence of an exemplary mhUBP2 expression construct (SEQ ID NO: 110).

FIG. 19 shows the sequence of an exemplary bsUBP3 expression construct (SEQ ID NO: 111). Attorney Docket No. 35327-522001 WO

FIG. 20 shows the sequence of an exemplary dcUBP4 expression construct (SEQ ID NO: 112).

FIG. 21 shows the sequence of an exemplary gtUBP5 expression construct (SEQ ID NO: 113).

FIG. 22 shows the sequence of an exemplary ctUBP6 expression construct (SEQ ID NO: 114).

FIG. 23 shows the sequence of an exemplary csUBP7 expression construct (SEQ ID NO: 115).

FIG. 24 shows the sequence of an exemplary taUBP8 expression construct (SEQ ID NO: 116).

FIG. 25 shows the sequence of an exemplary gkUBPIO expression construct (SEQ ID NO: 117).

FIG. 26 shows the sequence of an exemplary psUBPl 1 expression construct (SEQ ID NO: 118).

FIG. 27 shows the sequence of an exemplary teUBP12 expression construct (SEQ ID NO: 119).

FIG. 28 shows the sequence of an exemplary csUBP7_26C expression construct (SEQ ID NO: 120).

FIG. 29 shows the sequence of an exemplary csUBP7_27C expression construct (SEQ ID NO: 121).

FIG. 30 shows the sequence of an exemplary csUBP7_30C expression construct (SEQ ID NO: 122).

FIG. 31 shows the sequence of an exemplary csUBP7_65C expression construct (SEQ ID NO: 123).

FIG. 32 shows the sequence of an exemplary csUBP7_69C expression construct (SEQ ID NO: 124).

FIG. 33 shows the sequence of an exemplary csUBP7_90C expression construct (SEQ ID NO: 125).

FIG. 34 shows the sequence of an exemplary csUBP7_92C expression construct (SEQ ID NO: 126).

FIG. 35 shows the sequence of an exemplary csUBP7_92C expression construct (SEQ ID NO: 127). Attorney Docket No. 35327-522001 WO

FIG. 36 shows the sequence of an exemplary csUBP7_93C expression construct (SEQ ID NO: 128).

FIG. 37 shows the sequence of an exemplary csUBP7_95C expression construct (SEQ ID NO: 129).

FIG. 38 shows the sequence of an exemplary csUBP7_l 11C expression construct (SEQ ID NO: 130).

FIG. 39 shows the sequence of an exemplary csUBP7_l 14C expression construct (SEQ ID NO: 131).

FIG. 40 shows the sequence of an exemplary csUBP7_l 15C expression construct (SEQ ID NO: 132).

FIG. 41 shows the sequence of an exemplary csUBP7_l 16C expression construct (SEQ ID NO: 133).

FIG. 42 shows the sequence of an exemplary csUBP7_157C expression construct (SEQ ID NO: 134).

FIG. 43 shows the sequence of an exemplary csUBP7_158C expression construct (SEQ ID NO: 135).

FIG. 44 shows the sequence of an exemplary csUBP7_159C expression construct (SEQ ID NO: 136).

FIG. 45 shows the sequence of an exemplary csUBP7_186C expression construct (SEQ ID NO: 137).

FIG. 46 shows the sequence of an exemplary csUBP7_211C expression construct (SEQ ID NO: 138).

FIG. 47 shows the sequence of an exemplary csUBP7_238C expression construct (SEQ ID NO: 139).

FIG. 48 shows the sequence of an exemplary bsUBP3_76C expression construct (SEQ ID NO: 140).

FIG. 49 shows the sequence of an exemplary bsUBP3_77C expression construct (SEQ ID NO: 141).

FIG. 50 shows the sequence of an exemplary bsUBP3_78C expression construct (SEQ ID NO: 142).

FIG. 51 shows the sequence of an exemplary bsUBP3_79C expression construct (SEQ ID NO: 143). Attorney Docket No. 35327-522001 WO

FIG. 52 shows the sequence of an exemplary bsUBP3_145C expression construct (SEQ ID NO: 144).

FIG. 53 shows the sequence of an exemplary bsUBP3_172C expression construct (SEQ ID NO: 145).

FIG. 54 shows the sequence of an exemplary ctUBP6_95C expression construct (SEQ ID NO: 146).

FIG. 55 shows the sequence of an exemplary ctUBP6_96C expression construct (SEQ ID NO: 147).

FIG. 56 shows the sequence of an exemplary ctUBP6_97C expression construct (SEQ ID NO: 148).

FIG. 57 shows the sequence of an exemplary ctUBP6_98C expression construct (SEQ ID NO: 149).

FIG. 58 shows the sequence of an exemplary ctUBP6_164C expression construct (SEQ ID NO: 150).

FIG. 59 shows the sequence of an exemplary ctUBP6_191C expression construct (SEQ ID NO: 151).

FIG. 60 shows the sequence of an exemplary csUBP7_186C.l expression construct (SEQ ID NO: 152).

FIG. 61 shows the sequence of an exemplary csUBP7_186C.2 expression construct (SEQ ID NO: 153).

FIG. 62 shows the sequence of an exemplary csUBP7_186C.3 expression construct (SEQ ID NO: 154).

FIG. 63 shows the sequence of an exemplary csUBP7_186C.4 expression construct (SEQ ID NO: 155).

FIG. 64 shows the sequence of an exemplary csUBP7_186C.5 expression construct (SEQ ID NO: 156).

FIG. 65 shows the sequence of an exemplary csUBP7_186C.6 expression construct (SEQ ID NO: 157).

FIG. 66 shows the sequence of an exemplary csUBP7_186C.7 expression construct (SEQ ID NO: 158).

FIG. 67 shows the sequence of an exemplary csUBP7_186C.8 expression construct (SEQ ID NO: 159). Attorney Docket No. 35327-522001 WO

FIG. 68 shows the sequence of an exemplary csUBP7_186C9 expression construct (SEQ ID NO: 160).

FIG. 69 shows the sequence of an exemplary csUBP7_186C10 expression construct (SEQ ID NO: 161).

FIG. 70 shows the sequence of an exemplary csUBP7_186C.l 1 expression construct (SEQ ID NO: 162).

FIG. 71 shows the sequence of an exemplary csUBP7_186C12 expression construct (SEQ ID NO: 163).

FIG. 72 shows the sequence of an exemplary csUBP7_186C13 expression construct (SEQ ID NO: 164).

FIG. 73 shows the sequence of an exemplary csUBP7_186C14 expression construct (SEQ ID NO: 165).

FIG. 74 shows the sequence of an exemplary csUBP7_186C15 expression construct (SEQ ID NO: 166).

FIG. 75 shows the sequence of an exemplary csUBP7_186C16 expression construct (SEQ ID NO: 167).

FIG. 76 shows the sequence of an exemplary csUBP7_186C17 expression construct (SEQ ID NO: 168).

FIG. 77 shows the sequence of an exemplary csUBP7_186C18 expression construct (SEQ ID NO: 169).

FIG. 78 shows the sequence of an exemplary csUBP7_186C19 expression construct (SEQ ID NO: 170).

FIG. 79 shows the sequence of an exemplary csUBP7_186C20 expression construct (SEQ ID NO: 171).

FIG. 80 shows the sequence of an exemplary csUBP7_186C21 expression construct (SEQ ID NO: 172).

FIG. 81 shows the sequence of an exemplary csUBP7_186C22 expression construct (SEQ ID NO: 173).

FIG. 82 shows the sequence of an exemplary csUBP7_186C23 expression construct (SEQ ID NO: 174).

FIG. 83 shows the sequence of an exemplary csUBP7_186C24 expression construct (SEQ ID NO: 175). Attorney Docket No. 35327-522001 WO

FIG. 84 shows the sequence of an exemplary csUBP7_186C25 expression construct (SEQ ID NO: 176).

FIG. 85 shows the sequence of an exemplary csUBP7_186C26 expression construct (SEQ ID NO: 177).

FIG. 86 shows the sequence of an exemplary csUBP7_186C27 expression construct (SEQ ID NO: 178).

FIG. 87 shows the sequence of an exemplary csUBP7_186C28 expression construct (SEQ ID NO: 179).

FIG. 88 shows the sequence of an exemplary csUBP7_186C29 expression construct (SEQ ID NO: 180).

FIG. 89 shows the sequence of an exemplary csUBP7_186C30 expression construct (SEQ ID NO: 181).

FIG. 90 shows the sequence of an exemplary csUBP7_186C31 expression construct (SEQ ID NO: 182).

FIG. 91 shows the sequence of an exemplary csUBP7_186C32 expression construct (SEQ ID NO: 183).

FIG. 92 shows the sequence of an exemplary csUBP7_186C33 expression construct (SEQ ID NO: 184).

FIG. 93 shows the sequence of an exemplary csUBP7_186C34 expression construct (SEQ ID NO: 185).

FIG. 94 shows the sequence of an exemplary csUBP7_186C35 expression construct (SEQ ID NO: 186).

FIG. 95 shows the sequence of an exemplary csUBP7_186C36 expression construct (SEQ ID NO: 187).

FIG. 96 shows the sequence of an exemplary csUBP7_186C37 expression construct (SEQ ID NO: 188).

FIG. 97 shows the sequence of an exemplary csUBP7_186C38 expression construct (SEQ ID NO: 189).

FIG. 98 shows the sequence of an exemplary csUBP7_186C39 expression construct (SEQ ID NO: 190).

FIG. 99 shows the sequence of an exemplary csUBP7_26C_bZif expression construct (SEQ ID NO: 191). Attorney Docket No. 35327-522001 WO

FIG. 100 shows the sequence of an exemplary csUBP7_27C_bZif expression construct (SEQ ID NO: 192).

FIG. 101 shows the sequence of an exemplary csUBP7_30C_bZif expression construct (SEQ ID NO: 193).

FIG. 102 shows the sequence of an exemplary csUBP7_95C_bZif expression construct (SEQ ID NO: 194).

FIG. 103 shows the sequence of an exemplary csUBP7_186C.20_bZif expression construct (SEQ ID NO: 195).

FIG. 104 shows the sequence of an exemplary csUBP7 186C.114A_Imml expression construct (SEQ ID NO: 196).

FIG. 105 shows the sequence of an exemplary csUBP7 186C.114A_Imm2 expression construct (SEQ ID NO: 197).

FIG. 106 shows the sequence of an exemplary csUBP7 186C.114A_Imm3 expression construct (SEQ ID NO: 198).

FIG. 107 shows the sequence of an exemplary csUBP7 186C.114A_Imm4 expression construct (SEQ ID NO: 199).

FIG. 108 shows the sequence of an exemplary csUBP7 186C.114A_Imm5 expression construct (SEQ ID NO: 200).

FIG. 109 shows the sequence of an exemplary csUBP7 186C.114A_Imm6 expression construct (SEQ ID NO: 201).

FIG. 110 is a diagram relating to directly responsive partners and indirectly responsive partners in ngmFRET pathways.

DETAILED DESCRIPTION

Urea plays a significant role in the global nitrogen cycle, functioning both as a sink to remove excess nitrogen from eukaryotes and as a nitrogen source for prokaryotes. In humans, excess urea is removed from circulation by the kidneys. Levels of blood urea nitrogen therefore are used to assess, e.g., kidney function and the effectiveness of hemodialysis treatment. Urea also is assayed in food compositions such as bovine milk to assess feed efficiency, as well as in alcoholic beverages to detect levels that might result in the production of the carcinogen ethyl carbamate. In the environment, urea is measured to assess pollution resulting from agricultural (e.g., fertilizer run-off) and industrial activities. Attorney Docket No. 35327-522001 WO

Fluorescently responsive sensors (FRSs) based on engineered proteins that couple ligand-binding events to changes in the emission properties of fluorophores (being fluorescent by themselves and regardless of the presence of any other fluorophore/partner) or semi-synthetically incorporated chromophores have wide-ranging applications in cell biology and analytical chemistry. If the fluorescence emission spectrum of an engineered FRS changes shape in response to ligand binding such that the ratio of intensities at two appropriately chosen wavelengths reports on ligand concentration (dichromatic response), then ratiometric measurements can be used to monitor analyte concentrations. Ratiometry is essential for devices that rely on changes in fluorescence emission intensities, because it provides an internally consistent reference. The self-calibrating nature of a ratiometric measurement removes the necessity for carrying out on-board calibration tests prior to each measurement, obviating the need for multiple components and fluidic circuitry. Accordingly, reagentless, ratiometric fluorescent sensors have many uses in process engineering, environmental or clinical chemistry, including single-use point-of-care applications, wearable devices, or implanted "tattoos" that are interrogated transdermally.

The periplasmic binding protein (PBP) superfamily provide a rich source of FRSs, because PBPs combine a large diversity of ligand specificities with a common structural mechanism that is well suited to the construction of fluorescence signal transduction schemes. The three-dimensional PBP monomer structure comprises two α/β domains linked by a β-strand hinge. Binding of ligand is accompanied by a large hinge-bending motion that transitions the protein from an open to a closed state in which the ligand is enveloped within a cleft between the two domains. Semi-synthetic FRSs can be engineered with PBPs by site- specifically attaching single, thiol-reactive, environmentally sensitive fluorophores that respond to the ligand-mediated conformational change (FIGS. 1A-D). For example, semisynthetic, fluorescently labeled glucose-binding proteins in the periplasmic binding protein superfamily have been engineered successfully as reagentless, ratiometric glucose biosensors that can be used for point-of-care diagnostics and in vivo continuous glucose monitoring applications.

Urea plays a significant role in the global nitrogen cycle, functioning both as a sink to remove excess nitrogen from eukaryotes and as a nitrogen source for prokaryotes. In humans, excess urea is removed from circulation by the kidneys. Levels of blood nitrogen therefore are used to assess kidney function and the effectiveness of hemodialysis treatment. Urea also is assayed in food, including bovine milk to assess feed efficiency, and in alcoholic Attorney Docket No. 35327-522001 WO beverages to detect levels that might result in the production of the carcinogen ethyl carbamate. In the environment, urea is measured to assess pollution resulting from agricultural (fertilizer run-off) and industrial activities. Urea concentrations typically are measured enzymatically with urease. Enzyme activity is determined by measuring reaction product (protons, ammonium, bicarbonate), either colorimetrically in coupled enzyme assays, or with ion-selective electrodes, or a plethora of other physical techniques. Although these assays can perform well, all are sensitive to inhibition of urease activity, or alternative sources of product (e.g. pH fluctuations, dissolved C0 ₂ ); some require multiple reagents (e.g. coupled enzymes), or multi-component detectors (e.g. membranes and compartments of ion- selective electrodes). Here we report the development of a simple, single-component, reagentless assay based on robust, genetically engineered periplasmic urea-binding proteins that interact directly with urea to transduce concentrations into ratiometric fluorescent signals.

Biosensors

Biosensors are molecular recognition elements that transduce ligand-binding events into physical signals. Biosensors as detailed herein bind at least one ligand and emit a signal. A ligand-bound biosensor results in a signal that is different from the unbound biosensor. This difference facilitates detection of the at least one ligand and/or determination of ligand concentration. The biosensors may be used without the assistance of other reagents.

Described herein are novel engineered biosensors. These biosensors may have altered ligand-binding affinities, tailored ligand-binding specificities, and/or temperature dependencies of ligand binding or stability. For example, the herein described engineered urea biosensors provide high-accuracy information related to extended urea concentration ranges.

Binding of ligand mediates conformational changes in the biosensor, such as hinge-bending motions of the polypeptide. The conformational changes affect the environment of the reporter such that a change in the reporter-generated signal occurs. That is, without ligand bound, the biosensor results in signal generated from the reporter, and when ligand is bound, the signal generated from the reporter group changes. The ligand- bound biosensor results in a reporter-generated signal that is different from the unbound biosensor.

In some embodiments, the methods and compositions include a plurality of a Attorney Docket No. 35327-522001 WO single type of biosensor. The biosensors may be identical in structure and function. For example, the biosensors of a single type may have the same polypeptide, the same reporter, and the same ligand affinity.

In other embodiments, the methods and compositions include a plurality of different types of biosensors. A plurality of these different types of biosensors may be arranged or incorporated in a panel. As used herein, a "panel" refers to two or more biosensors. The two or more biosensors may be different from each other. The biosensors may differ in structure and/or function. Biosensors may differ in polypeptide sequence, reporter, ligand affinities, or a combination thereof. Accordingly, there may be different types of biosensors. In some embodiments, each biosensor in the panel comprises the same reporter group. In some embodiments, each biosensor in the panel comprises a different reporter group. The panel may include at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50, at least 55, at least 60, at least 65, at least 70, at least 75, at least 80, at least 85, at least 90, at least 95, or at least 100 biosensors.

The panel of biosensors includes at least one sensor element. "Sensor element" refers to a single spot, site, location, or well for the at least one biosensor, to which a sample or aliquot thereof may be applied. The panel may be a composite sensor or an array.

In some embodiments, the panel is a composite sensor. In a composite sensor, each sensor element includes a mixture of two or more different biosensors. In some embodiments, the composite sensor includes one sensor element. In some embodiments, the composite sensor includes two or more sensor elements. In some embodiments, signals are measured from a composite sensor in which the signals arise from one or more biosensors in the sensor element. For example, signals may be measured from a composite sensor in which the signals arise from a subset of the total number of biosensors in the sensor element. For example, signals may be measured from a composite sensor in which the signals arise from two of five biosensors in the sensor element.

In some embodiments, the panel is an array. In an array, each sensor element includes a single type of biosensor. An array comprises a plurality of individually and spatially localized sensor elements. Each sensor element includes a biosensor that is different than or the same as the biosensor of a different sensor element. In some embodiments, Attorney Docket No. 35327-522001 WO signals are measured from an array in which the signals arise separately from two or more selected biosensors in separate sensor elements. An array may comprise a plurality of sensor elements of a variety of sizes and configurations. An array may comprise a plurality of sensor elements arranged linearly. For example, an array may comprise a plurality of micrometer- sized sensor elements arranged in a single row. An array may comprise a plurality of sensor elements arranged in a grid. The grid may be two- or three-dimensional. In some

embodiments, the grid is a spatially addressable grid. In some embodiments, the biosensors are incorporated into an array, such as a multichannel or multiplexed array.

The biosensors of the present disclosure can be used in any setting where

urea detection is required or desired, such a medical setting (e.g., determining the level of blood urea in a subject), environmental setting (e.g., determining the level of urea in an environmental sample), biological setting (e.g., determining the presence or amount of urea in a reaction), or in process engineering, such as monitoring the amount of urea in a

fermentation reaction (e.g., a bacterial culture, a yeast culture, beer/wine production, etc.). Other examples include, but are not limited to, uses in the food industry (Suleiman et al., 1992, In: Biosensor Design and Application: Mathewson and Finley Eds; American

Chemical Society, Washington, DC vol. 511); in clinical chemistry (Wilkins et al., 1996, Med. Eng. Phys., 18, 273-288; Pickup, Tr., 1993, Biotech., 11, 285-291; Meyerhoff et al., 1966, Endricon, 6, 51-58; Riklin et al., 1995, Nature, 376, 672-675); Willner et al., 1996, J. Am. Chem. Soc, 118, 10321-10322); as the basis for the construction of a fluorescent flow cell containing immobilized ligand binding protein-FAST conjugates (see, e.g., Wilkins et al., 1966, Med. Eng. Phys., 18, 273-288; Pickup, Tr., 1993, Biotech., 11, 285-291; Meyerhoff et al., 1966, Endricon., 6, 51 ; Group, 1993, New Engl. J. Med, 329, 977-986; Gough et al., 1995, Diabetes, 44, 1005-1009); and in an implantable devices.

The biosensors as detailed herein may be administered in a variety of ways known by those of skill in the art, as appropriate for each application. Biosensors may be provided in a solution. The solution may be buffered. Biosensors may be provided in a solution and mixed directly with a sample. In some embodiments, a biosensor is immobilized onto a surface. Biosensors may be immobilized within a disposable cartridge into which a sample may be introduced or applied. Biosensors may be implanted or incorporated in a wearable device. The biosensor may be provided as an optode.

The biosensor may be attached to or incorporated in a wearable device. Wearable devices may include, for example, adhesive strips, patches, and contact lenses. The biosensor Attorney Docket No. 35327-522001 WO may be configured for placement in contact with a subject's skin or mucosal surface. In some embodiments, the biosensor is configured as an adhesive strip. In some embodiments, the biosensor is configured within or on the surface of a contact lens. In some embodiments, the contact lens is formed from a transparent substrate shaped to be worn directly over a subject's eye, as described in, for example, U.S. Patent No. 8,608,310.

The biosensor may be implanted. The biosensor may be implanted in a subject's body. The biosensor may be implanted in a subject's blood vessel, vein, eye, natural or artificial pancreas, skin, or anywhere in the alimentary canal including the stomach, intestine and esophagus. The biosensor may be implanted in a subject with a microbead. In some embodiments, the biosensor is configured to be implanted in the skin. The biosensor may be implanted in a subject sub-dermally. The biosensor may generate the signal trans-dermally. In some embodiments, the biosensor may be implanted in a subject with transdermal microbeads, wherein the optical signals can be transmitted remotely between the biosensor and detecting device.

In some embodiments, the biosensor is administered as an optode. As used herein, "optode" refers to an optical fiber with a single biosensor, or a composite biosensor, immobilized at the surface or at the end. An "optode" may also be referred to as an

"optrode." In some embodiments, the biosensor is implanted in a subject as an optode. The optode may be incorporated with or into a needle. The optode may be incorporated with a probe such as endoscopy or colonoscopy probes. The optode may be used in a tumor, near a tumor, or at the periphery of a tumor. In some embodiments, the biosensor may be implanted in a subject as an optode, wherein the optical signals can be transmitted between the biosensor and detecting device using physical links. In some embodiments, the biosensor is administered as an optode to a sample or reaction. The optode may be contacted with a sample or reaction. In some embodiments, an optode is used to continuously or episodically monitor a ligand in a sample or reaction.

Methods Of Detecting The Presence Of A Ligand

Provided herein is a method of detecting the presence of a ligand in a sample. The method may include contacting the biosensor with the sample; measuring a signal from the biosensor; and comparing the signal to a ligand-free control. A difference in signal indicates the presence of ligand in the sample. Attorney Docket No. 35327-522001 WO

Also provided herein is a method of detecting the presence of urea in a sample. The method may include (a) providing a urea biosensor disclosed herein in which the reporter group is attached the urea so that a signal transduced by the reporter group when the urea is bound to urea differs from a signal transduced by the reporter group when the urea is not bound to urea; (b) contacting the biosensor with the test sample under conditions such that the biosensor can bind to urea present in the test sample; and (c) comparing the signal transduced by the reporter group when the biosensor is contacted with the test sample with the signal transduced by the reporter group when the biosensor is contacted with a urea-free control sample, wherein a difference in the signal transduced by the reporter group when the biosensor is contacted with the test sample, as compared to when the biosensor is contacted with the control sample, indicates that the test sample contains urea.

Methods Of Determining The Concentration Of A Ligand

Provided herein is a method of determining the concentration of a ligand in a sample. The method may include contacting the biosensor with the sample; measuring a signal from the biosensor; and comparing the signal to a standard hyperbolic ligand binding curve to determine the concentration of ligand in the test sample. The standard hyperbolic ligand binding curve may be prepared by measuring the signal transduced by the biosensor when contacted with control samples containing known concentrations of ligand.

Another aspect of the present disclosure provides a method of determining the concentration of urea in a test sample comprising, consisting of, or consisting essentially of: (a) providing a urea biosensor comprising a urea-binding protein as described herein in which the reporter group is attached the urea-binding protein so that a signal transduced by the reporter group when the urea-binding protein is bound to urea differs from a signal transduced by the reporter group when the urea-binding protein is not bound to urea; (b) contacting the biosensor with the test sample under conditions such that the biosensor can bind to urea present in the test sample; and (c) comparing the signal transduced by the reporter group when the biosensor is contacted with the test sample with a standard hyperbolic urea binding curve prepared by measuring the signal transduced by the reporter group when the biosensor is contacted with control samples containing known quantities of urea to determine the concentration of urea in the test sample. Attorney Docket No. 35327-522001 WO

Methods Of Monitoring The Presence Of A Ligand

The present invention is directed to a method of episodically or continuously monitoring the presence of a ligand in a reaction. In certain embodiments, the biosensors may be used in the continuous monitoring of urea in a reaction. In certain embodiments, the urea sensors may be used in episodic monitoring of sample aliquots.

The method of episodically or continuously monitoring the presence of a ligand in a reaction may include contacting the biosensor with the reaction; maintaining the reaction under conditions such that the polypeptide is capable of binding ligand present in the reaction; and episodically or continuously monitoring the signal from the biosensor in the reaction.

The method of episodically or continuously monitoring the presence of a ligand in a reaction may include contacting the biosensor with the reaction; maintaining the reaction under conditions such that the polypeptide is capable of binding ligand present in the reaction; episodically or continuously monitoring the signal from the biosensor in the reaction; and comparing the signal to a standard hyperbolic ligand binding curve to determine the concentration of ligand in the test sample. The standard hyperbolic ligand binding curve may be prepared by measuring the signal transduced by the biosensor when contacted with control samples containing known concentrations of ligand.

In some embodiments, the method further includes comparing the signal to a ligand- free control, wherein a difference in signal indicates the presence of ligand in the reaction.

In some embodiments, the method further includes comparing the signal to a standard hyperbolic ligand binding curve to determine the concentration of ligand in the test sample. The standard hyperbolic ligand binding curve may be prepared by measuring the signal transduced by the biosensor when contacted with control samples containing known concentrations of ligand.

Another aspect of the present disclosure provides a method of continuously monitoring the presence of urea in a reaction comprising, consisting of, or consisting essentially of: (a) providing a urea biosensor as described herein in which the reporter group is attached a urea-binding protein so that a signal transduced by the reporter group when the urea-binding protein is bound to urea differs from a signal transduced by the reporter group when the urea-binding protein is not bound to urea; (b) maintaining the biosensor within the reaction and under conditions such that the biosensor can bind to urea present in the reaction; (c) continuously monitoring the signal transduced by the reporter group when the biosensor is Attorney Docket No. 35327-522001 WO contacted with the urea present in the reaction; and optionally (d) comparing the signal transduced by the reporter group when the biosensor is contacted with the urea present in the reaction with the signal transduced by the reporter group when the biosensor is contacted with a urea-free control sample, wherein a difference in the signal transduced by the reporter group when the biosensor is contacted with the urea present in the reaction, as compared to when the biosensor is contacted with the control sample, indicates urea is present in the reaction.

Yet another aspect of the present disclosure provides a method of continuously monitoring the concentration of urea in a reaction comprising, consisting of, or consisting essentially of: (a) providing a urea biosensor comprising a urea biosensor as described herein in which the reporter group is attached a urea-binding protein so that a signal transduced by the reporter group when the urea-binding protein is bound to urea differs from a signal transduced by the reporter group when the urea-binding protein is not bound to urea; (b) maintaining the biosensor within the reaction under conditions such that the biosensor can bind to urea present in the reaction; and (c) continuously monitoring the signal transduced by the reporter group when the biosensor is contacted with the urea present in the reaction; and (d) comparing the signal transduced by the reporter group when the biosensor is contacted with the urea present in the reaction with a standard hyperbolic urea binding curve prepared by measuring the signal transduced by the reporter group when the biosensor is contacted with control samples containing known quantities of urea to determine the concentration of urea in the reaction.

Non-Limiting Examples Described Herein

To construct non-limiting examples of urea sensors based on engineered PBPs, we used bioinformatics to accurately identify urea-binding proteins (UBPs) in publicly available prokaryotic genomic sequences. Starting with the sequences of two genetically and biochemically characterized periplasmic urea-binding proteins (Valladeres, 2002, Molec. Microbiol, 43, 703-715; Beckers, 2004, J. Bacteriol, 186, 7645-7652; Siewe, 1998, Arch. Microbiol., 169, 411-416), we identified distantly related urea-binding proteins in thermophilic bacteria. To accurately define the binding function in the set of initial sequence homologs, we applied a combination of genomic contextual and three-dimensional protein structural information. The proteins for a small subset of sequences identified in this manner were prepared by heterologous expression of synthetic genes, optimized for heterologous Attorney Docket No. 35327-522001 WO expression in E. coli (Allert, Cox and Hellinga, 2010, J Mol Biol, 402, 905-18). The urea- binding properties of these proteins were measured using a thermal stability shift assay (Layton and Hellinga, 2010, Biochemistry, 49, 10831-41). All the proteins that expressed in soluble form bound urea with micromolar or better affinity, confirming the accuracy of the gene function prediction.

The structure of the UBP from Caldicellulosiruptor saccharolyticus (csUBP7), a thermophilic bacterium, was determined by X-ray crystallography. This structure was used to refine the bioinformatic definition of urea-binding proteins, and in the protein engineering strategy used to convert csUBP7 into a non-limiting example of a fluorescently responsive urea biosensor.

Conjugates of the environmentally sensitive, thiol-reactive fluorophores Acrylodan and Badan were attached to a series of single-cysteine mutants of csUBP7 and two other homologs and screened for fluorescent urea responses. Two csUBP7 conjugates, csUBP95C and csUBP186C, gave good ratiometric responses. The performance of the csUBP186C conjugate was further optimized by constructing a doubly labeled sensor in which the environmentally sensitive response of Alexa532 placed at 186C was coupled via fluorescence resonance energy transfer to an Acrylodan placed at thiols in a fusion domain. Under the right conditions, such non-geometrically modulated FRET (ngmFRET) pairs can convert linear quenching effects into ratiometric responses.

Matching of affinities with pathophysiological concentration ranges [below (less than about 2 mM), within (about 2 mM to about 7 mM), or above (greater than about 7 mM) normal human serum levels] is essential for constructing sensors that perform with sufficient precision to enable accurate clinical chemometrics. Of the csUBP7 conjugates that gave ratiometric response, csUBP7 186C was selected for further mutagenesis to "tune" its affinity and place the mid-point of the binding curve within the concentration range of urea in blood (Burtis, 2012, Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Elsevier) (1.8-7.1 mM) whereas csUBP7 95C already was in the correct clinical range. Mutants of csUBP7 186C were identified with urea affinities in the 0.001-100 mM range. One of these, Q114A, was selected for further optimization of its fluorescence. The engineered csUBP7 mutants and ngmFRET constructs reported here therefore comprise a robust set of sensors for detecting urea in the clinical pathophysiological concentration range.

Immobilization of FRSs on solid surfaces with minimal perturbation of the molecular sensing mechanism is an important step for incorporating biosensors into devices. Attorney Docket No. 35327-522001 WO

Immobilization enables retention of the sensor within the sampling element (e.g. optode surface or implanted bead for in vivo sensing applications; or in a sample-handling cartridge for ex vivo sensing). Immobilization also may provide spatial localization to provide the necessary addressability of different elements in a multi-sensor array comprising sensors that differ in their engineered affinities for coverage of a wide range of urea concentrations, or sensors that each detect distinct analytes.

Ex vivo clinical chemistries such as point-of-care applications require that the FRS is incorporated into a cartridge into which a sample is introduced at the time of measurement. Such "disposables" need to have a long shelf life that preferably does not require temperature control (e.g. refrigeration) for storage or distribution. It is preferable to incorporate immobilized protein in a stable, dried form in such disposables. The resistance to denaturation of thermostable proteins minimizes the need for temperature control during manufacturing and storage, and may extend to the long-term stability of a desiccated state.

The spectral response, binding affinity, and thermostability of the robust thermostable UBP FRSs reported here are conserved following site-specific immobilization on beads. Furthermore, these properties are generally retained upon reconstitution following drying. The engineered proteins provided herein are useful for robust, high-precision, wide-dynamic range urea sensing applications, including continuous monitoring, point-of-care, wearable sensor systems.

General Definitions

Unless specifically defined otherwise, all technical and scientific terms used herein shall be taken to have the same meaning as commonly understood by one of ordinary skill in the art (e.g., in cell culture, molecular genetics, and biochemistry).

As used herein, the term "about" in the context of a numerical value or range means ±10% of the numerical value or range recited or claimed, unless the context requires a more limited range.

In the descriptions above and in the claims, phrases such as "at least one of or "one or more of may occur followed by a conjunctive list of elements or features. The term "and/or" may also occur in a list of two or more elements or features. Unless otherwise implicitly or explicitly contradicted by the context in which it is used, such a phrase is intended to mean any of the listed elements or features individually or any of the recited elements or features in combination with any of the other recited elements or features. For Attorney Docket No. 35327-522001 WO example, the phrases "at least one of A and Β;" "one or more of A and Β;" and "A and/or B" are each intended to mean "A alone, B alone, or A and B together." A similar interpretation is also intended for lists including three or more items. For example, the phrases "at least one of A, B, and C;" "one or more of A, B, and C;" and "A, B, and/or C" are each intended to mean "A alone, B alone, C alone, A and B together, A and C together, B and C together, or A and B and C together." In addition, use of the term "based on," above and in the claims is intended to mean, "based at least in part on," such that an unrecited feature or element is also permissible

It is understood that where a parameter range is provided, all integers within that range, and tenths thereof, are also provided by the invention. For example, "0.2-5 mg" is a disclosure of 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg etc. up to and including 5.0 mg.

A small molecule is a compound that is less than 2000 daltons in mass. The molecular mass of the small molecule is preferably less than 1000 daltons, more preferably less than 600 daltons, e.g., the compound is less than 500 daltons, 400 daltons, 300 daltons, 200 daltons, or 100 daltons.

As used herein, an "isolated" or "purified" nucleic acid molecule, polynucleotide, polypeptide, or protein, is substantially free of other cellular material, or culture medium when produced by recombinant techniques, or chemical precursors or other chemicals when chemically synthesized. Purified compounds are at least 60% by weight (dry weight) the compound of interest. Preferably, the preparation is at least 75%, more preferably at least 90%, and most preferably at least 99%, by weight the compound of interest. For example, a purified compound is one that is at least 90%, 91%, 92%, 93%, 94%, 95%, 98%, 99%, or 100% (w/w) of the desired compound by weight. Purity is measured by any appropriate standard method, for example, by column chromatography, thin layer chromatography, or high-performance liquid chromatography (HPLC) analysis. A purified or isolated polynucleotide (ribonucleic acid (RNA) or deoxyribonucleic acid (DNA)) is free of the genes/nucleic acids or sequences/amino acids that flank it in its naturally-occurring state. Purified also defines a degree of sterility that is safe for administration to a human subject, e.g., lacking infectious or toxic agents.

Similarly, by "substantially pure" is meant a nucleotide or polypeptide that has been separated from the components that naturally accompany it. Typically, the nucleotides and polypeptides are substantially pure when they are at least 60%, 70%, 80%, 90%, 95%, or Attorney Docket No. 35327-522001 WO even 99%, by weight, free from the proteins and naturally-occurring organic molecules with they are naturally associated.

The transitional term "comprising," which is synonymous with "including,"

"containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. By contrast, the transitional phrase

"consisting of excludes any element, step, or ingredient not specified in the claim. The transitional phrase "consisting essentially of limits the scope of a claim to the specified materials or steps "and those that do not materially affect the basic and novel

characteristic(s)" of the claimed invention.

"Subject" as used herein refers to any organism from which a biological sample is obtained. For example, the sample is a biological fluid or tissue. For example, a subject is one who wants or is in need of detecting ligand or determining the concentration of ligand with the herein described biosensors. The subject may be a human or a non-human animal. The subject may be a mammal. The mammal may be a primate or a non-primate. The mammal can be a primate such as a human; a non-primate such as, for example, dog, cat, horse, cow, pig, mouse, rat, camel, llama, goat, rabbit, sheep, hamster, and guinea pig; or non-human primate such as, for example, monkey, chimpanzee, gorilla, orangutan, and gibbon. The subject may be of any age or stage of development, such as, for example, an adult, an adolescent, or an infant.

As used herein, an "expression vector" is a DNA or RNA vector that is capable of effecting expression of one or more polynucleotides. Preferably, the expression vector is also capable of replicating within the host cell. Expression vectors can be either prokaryotic or eukaryotic, and are typically include plasmids. Expression vectors of the present invention include any vectors that function (i.e., direct gene expression) in host cells of the present invention, including in one of the prokaryotic or eukaryotic cells described herein, e.g., gram- positive, gram-negative, pathogenic, non-pathogenic, commensal, cocci, bacillus, or spiral- shaped bacterial cells; archaeal cells; or protozoan, algal, fungi, yeast, plant, animal, vertebrate, invertebrate, arthropod, mammalian, rodent, primate, or human cells. Expression vectors of the present invention contain regulatory sequences such as transcription control sequences, translation control sequences, origins of replication, and other regulatory sequences that are compatible with the host cell and that control the expression of a polynucleotide. In particular, expression vectors of the present invention include transcription control sequences. Transcription control sequences are sequences which control the initiation, Attorney Docket No. 35327-522001 WO elongation, and termination of transcription. Particularly important transcription control sequences are those which control transcription initiation such as promoter, enhancer, operator and repressor sequences. Suitable transcription control sequences include any transcription control sequence that can function in at least one of the cells of the present invention. A variety of such transcription control sequences are known to those skilled in the art.

As used herein, the singular forms "a," "an," and "the" include the plural reference unless the context clearly dictates otherwise. Thus, for example, a reference to "a disease," "a disease state", or "a nucleic acid" is a reference to one or more such embodiments, and includes equivalents thereof known to those skilled in the art and so forth.

As used herein, "pharmaceutically acceptable" carrier or excipient refers to a carrier or excipient that is suitable for use with humans and/or animals without undue adverse side effects (such as toxicity, irritation, and allergic response) commensurate with a reasonable benefit/risk ratio. It can be, e.g., a pharmaceutically acceptable solvent, suspending agent or vehicle, for delivering the instant compounds to the subject.

The term "diagnosis" refers to a determination that a disease is present in the subject. Similarly, the term "prognosis" refers to a relative probability that a certain future outcome may occur in the subject. For example, in the context of the present disclosure, prognosis can refer to the likelihood that an individual will develop a disease, or the likely severity of the disease (e.g., severity of symptoms, rate of functional decline, survival, etc.).

Unless required otherwise by context, the terms "polypeptide" and "protein" are used interchangeably.

A polypeptide or class of polypeptides may be defined by the extent of identity (% identity) of its amino acid sequence to a reference amino acid sequence, or by having a greater % identity to one reference amino acid sequence than to another. A variant of any of genes or gene products disclosed herein may have, e.g., 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid or amino acid sequences described herein. The term "% identity," in the context of two or more nucleic acid or polypeptide sequences, refers to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same, when compared and aligned for maximum correspondence, as measured using a sequence comparison algorithm or by visual inspection. For example, % identity is relative to the entire length of the coding regions of the sequences being compared, or the length of a Attorney Docket No. 35327-522001 WO particular fragment or functional domain thereof. Variants as disclosed herein also include homologs, orthologs, or paralogs of the genes or gene products described herein. In some embodiments, variants may demonstrate a percentage of homology or identity, for example, at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity conserved domains important for biological function, e.g., in a functional domain, e.g. a ligand-binding or catalytic domain.

For sequence comparison, one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. The sequence comparison algorithm then calculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters. Percent identity is determined using BLAST. For the BLAST searches, the following parameters were employed: (1) Expect threshold is 10; (2) Gap cost is Existence: 11 and Extension: 1; (3) The Matrix employed is BLOSUM62; (4) The filter for low complexity regions is "on."

The present invention also provides for functional fragments of the genes or gene products described herein. A fragment of a protein is characterized by a length (number of amino acids) that is less than the length of the full length mature form of the protein. A fragment, in the case of these sequences and all others provided herein, may be a part of the whole that is less than the whole. Moreover, a fragment ranges in size from a single nucleotide or amino acid within a polynucleotide or polypeptide sequence to one fewer nucleotide or amino acid than the entire polynucleotide or polypeptide sequence. Finally, a fragment is defined as any portion of a complete polynucleotide or polypeptide sequence that is intermediate between the extremes defined above.

For example, fragments of any of the proteins or enzymes disclosed herein or encoded by any of the genes disclosed herein can be 10 to 20 amino acids, 10 to 30 amino acids, 10 to 40 amino acids, 10 to 50 amino acids, 10 to 60 amino acids, 10 to 70 amino acids, 10 to 80 amino acids, 10 to 90 amino acids, 10 to 100 amino acids, 50 to 100 amino acids, 75 to 125 amino acids, 100 to 150 amino acids, 150 to 200 amino acids, 200 to 250 amino acids, 250 to 300 amino acids, 300 to 350, 300 to 375, or 350 to 400 amino acids. The fragments encompassed in the present subject matter comprise fragments that retain functional fragments. As such, the fragments preferably retain the binding domains that are required or are important for functional activity. Fragments can be determined or generated by using the Attorney Docket No. 35327-522001 WO sequence information herein, and the fragments can be tested for functional activity using standard methods known in the art. For example, the encoded protein can be expressed by any recombinant technology known in the art and the binding activity of the protein can be determined.

As used herein a "biologically active" fragment is a portion of a polypeptide which maintains an activity of a full-length reference polypeptide. Biologically active fragments as used herein exclude the full-length polypeptide. Biologically active fragments can be any size as long as they maintain the defined activity. Preferably, the biologically active fragment maintains at least 10%, at least 50%, at least 75% or at least 90%, of the activity of the full length protein.

Amino acid sequence variants/mutants of the polypeptides of the defined herein can be prepared by introducing appropriate nucleotide changes into a nucleic acid defined herein, or by in vitro synthesis of the desired polypeptide. Such variants/mutants include, for example, deletions, insertions or substitutions of residues within the amino acid sequence. A combination of deletion, insertion and substitution can be made to arrive at the final construct, provided that the final peptide product possesses the desired activity and/or specificity.

Mutant (altered) peptides can be prepared using any technique known in the art. For example, a polynucleotide defined herein can be subjected to in vitro mutagenesis or DNA shuffling techniques as broadly described by Harayama (1998). Products derived from mutated/altered DNA can readily be screened using techniques described herein to determine if they possess, for example, urea binding activity.

In designing amino acid sequence mutants, the location of the mutation site and the nature of the mutation will depend on characteristic(s) to be modified. The sites for mutation can be modified individually or in series, e.g., by (1) substituting first with conservative amino acid choices and then with more radical selections depending upon the results achieved, (2) deleting the target residue, or (3) inserting other residues adjacent to the located site.

Amino acid sequence deletions generally range from about 1 to 15 residues, more preferably about 1 to 10 residues and typically about 1 to 5 contiguous residues. In some embodiments, a mutated or modified protein does not comprise any deletions or insertions. In various embodiments, a mutated or modified protein has less than about 10, 9, 8, 7, 6, 5, 4, 3, or 2 deleted or inserted amino acids. Attorney Docket No. 35327-522001 WO

Substitution mutants have at least one amino acid residue in the polypeptide molecule removed and a different residue inserted in its place. Sites may be substituted in a relatively conservative manner in order to maintain activity and/or specificity. Such conservative substitutions are shown in the table below under the heading of "exemplary substitutions."

In certain embodiments, a mutant/variant polypeptide has only, or not more than, one or two or three or four conservative amino acid changes when compared to a naturally occurring polypeptide. Details of conservative amino acid changes are provided in the table below. As the skilled person would be aware, such minor changes can reasonably be predicted not to alter the activity of the polypeptide when expressed in a recombinant cell.

Exemplary Substitutions

Attorney Docket No. 35327-522001 WO

Mutations can be introduced into a nucleic acid sequence such that the encoded amino acid sequence is altered by standard techniques, such as site-directed mutagenesis and PCR- mediated mutagenesis. Preferably, conservative amino acid substitutions are made at one or more predicted non-essential amino acid residues. A "conservative amino acid substitution" is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art. Certain amino acids have side chains with more than one classifiable characteristic. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, tryptophan, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tyrosine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Thus, a predicted nonessential amino acid residue in a given polypeptide is replaced with another amino acid residue from the same side chain family. Alternatively, in another embodiment, mutations can be introduced randomly along all or part of a given coding sequence, such as by saturation mutagenesis, and the resultant mutants can be screened for given polypeptide biological activity to identify mutants that retain activity. Conversely, the invention also provides for variants with mutations that enhance or increase the endogenous biological activity. Following mutagenesis of the nucleic acid sequence, the encoded protein can be expressed by any recombinant technology known in the art and the activity/specificity of the protein can be determined. An increase, decrease, or elimination of a given biological activity of the variants disclosed herein can be readily measured by the ordinary person skilled in the art, i.e., by measuring the capability for binding a ligand and/or signal transduction.

In various embodiments, a polypeptide comprises mutations such that 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, or less than about 10, 9, 8, 7, 6, 5, 4, 3, or 2 amino acids is substituted with a cysteine and/or a lysine.

Polypeptides can be produced in a variety of ways, including production and recovery of natural polypeptides or recombinant polypeptides according to methods known in the art. In one embodiment, a recombinant polypeptide is produced by culturing a cell capable of expressing the polypeptide under conditions effective to produce the polypeptide, such as a host cell defined herein. Attorney Docket No. 35327-522001 WO

Key to the Sequence Listing

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135 Exemplary nucleotide sequence encoding csUBP7_158C Attorney Docket No. 35327-522001 WO

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The terms "bZif ' and "βΖϊΙ" are used synonymously herein.

Exemplary amino acid sequences are listed below for convenience:

mpUBPl (SEQ ID NO: 12)

MKVGVLHSLSGTMAISETTLKD LMMVEEQNK GGLLGK LEAVVVDPA

SNWPLFAEKARELLTEDQVDVIFGAWTSVSRKSVLPVIEELNGLMFYPVQ

YEGEESSYNVFYTGAAPNQQAIPAVNYLKDELGVERWVLAGTDYVYPRTT

NKILEAYLKDMGVAEDDIMINYTPFGHSDWQSIVSDIKKFGSAGKKTAW

STINGDANVPFYKELGNQGISSEDIPWAFSVGEEELSGLDTAPLVGHLA

AWNYFQSVETDENEEFITKWQAYTKNPERVTNDPMEATFIGFNMWANAVT

EAGTTDVDAVEKAMIGQETPNLTGGIAVMNKNHHLSKPVLIGEIQDDGQF

ETVWETDGWPGDAWSDFLPGSKDLVADWTDPLKAGNYNTETKMASGQNY

GGSHHHHHH* *

mhUBP2 (SEQ ID NO: 13)

MKVGILHSLSGTMAISETALKDTMLMLIEKQNEAGGVLGRQLEPWVDPA

SNWPLFAEKARELLEKEKVDVIFGNWTSVSRKSVLPWEELNGLLFYPVQ

YEGEESSENVFYTGAAPNQQAIPAVDYLMNDLGVERWVLAGTDYVYPRTT

NKILETYLKDKGVAAGDIMINYTPFGHSDWQTIVSDIKKFGSAGKKTAW

STINGDANVPFYRELGNQGISATDIPVVAFSVGEQELSGIDTAPLVGHLA

AWNY MSVDNDANYDFIDAWVAYKGDDAAVTNDPMEAHYIGF MYVEAVK

KAGTTDVDEVKDAIIGVSVPNLTGGYATMMPNHHITKPVLIGEIQDNGQF

SWWETPSTVAGDAWSDFLPGSKDLISDWRAPLRAGNFNWTGKAGGGSA

DVASNGGSHHHHHH* * Attorney Docket No. 35327-522001 WO bsUBP3 (SEQ ID NO: 14)

MKVGILHSLSGTMAISEVSVHDAELIAIQEINQKGGVLGK LEPWEDGA

SDWPTYAEKMR LLQQDKVAAVFGGWTSASR AMLPVVEQNNGLLFYPVQ

YEGMETSPNIFYTGATTNQQIVPAVDWLLKNKGK FFLIGSDYVFPRTAN

KIKAQVKAGGGEIAGEEYTPLGHTNYSTLVSKIKEKQPDVIFNTLNGDS

NVAFFKQLKDAGISADDMPVMSASVAEEEIRGIGPDVLKGHYAVWNYFQT

TNTSENQTFVKN^KECMNGDSRVTSDPIEAGYNAVYLWAAAVEKAKSFDVD

KVK AADGISFKAPGGTVKIDGDTQHLYKTVRIGQITGDGQFKEVWNSGE

P VKPDPYLKTYDWAKGLSKGGSHHHHHH* *

dcUBP4 (SEQ ID NO: 15)

MTIKVGILHSLSGTMAISEVSVKDAELMAIEEINASGGLLGKKIEPVIED

GASDWPTFAEKAK LLQQDKVAVIFGGWTSASRKAMLPWEENNGLLFYP

VQYEGLESSPNIFYTGAEPSQQIVPAVSWLLENRGKKFYLLGSDYVFPRT

ANKIKAQLKAKGGE GEEYTPLGHTDYSTIINKIKAAKPEIIFNTLNG

DSNVAFFKQLKDAGITSKDITVMSVSIAEEEIRGIGPQNIAGHLAVWNYF

QTTDTPENKEFVKf FKTKYGQDRVTDDPIEAGYFGVYLWAEAVK ANSTD

VGKVKEAIKTVEFQAPEGLVKINGENQHTWKTVRIGEVQPDGQFKELWNS

GGPVKPDP YLKGYEWAKGLSNGGSHHHHHH* *

gtUBP5 (SEQ ID NO: 16)

MASSAVDEVKEKPKETSASETGDTVKVGILHSLSGTMAISEVSLRDAELM

AIEEINKSGGLLGK IEPVIEDGASDWPTFAEKAK LLQKDKVAAIFGGW

TSASRKAMLPWEQNNGLLWYPVQYEGMESSPNIFYTGATTNQQIVPAVS

WLLENRGKRFFLLGSDYVFPRTANKIIKAQLKAEGGQLVGEEYTPLGHTD

YSTIINKIKEVKPDVVFNTLNGDSNVAFFKQLKDAGITAKDVTVMSVSIA

EEEIRGIGGDVLAGHLAVWTST^QSTDTPENKAFVEKYK KYGKERVTDDP

EAAYFAVHLWAEAVKKAGSFDVDKVK AADGIEYKAPGGTVKIDGETQH

TWXIVRIGEIQANGQFKELWNSGKAVKPDPYLKSYPWAKNLNGGSHHHHH

j _j ** ctUBP6 (SEQ ID NO: 17)

MVEEPVDNKPGTDTSAEDTIKVGILHSLSGTMAISEVSLKDAELMAIEEI

NQAGGLLGK IEPVIEDGASDWPTFAEKAKKLLQNDKVATVFGCWTSASR

KAVLPVFEENNGLLWYPVQYEGMESSPNIFYTGAAPNQQIVPAVEWLLEN

KGKRFFLLGSDYVFPRTANKIIKAQLSAIGGELIAEEYTPLGHTDYSTIV

NKIKTAKPDWFNTLNGDSNVAFFKQLKDAGITSEDITVCSVSVAEEEIR

GIGAENIKGHLVSWNYYQTTDTPENKEFVEKYKSKYGSDRVTDDPIEAAY

IAVHLWAEAVK AGSFEVEKVKEAAKGLEFKAPEGLVKIEGENQHLWKPV

RIGEVQEDGLKEIWSTSEAVRPDPYLKTYDWAKGLSDGGSHHHHHH**

csUBP7 (SEQ ID NO: 18)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

WEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVVVGEEYTPLGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI Attorney Docket No. 35327-522001 WO

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

taUBP8 (SEQ ID NO: 19)

MKSGYANPJIDFIKASAAVITLHTIAPALVWPSPKKIKVGVLHSLSGTMAI

SEVHVKNATLLAEEINRKGGVLGYTIEPIIEDGASDPATFAQKAQKLIL

MDKWTVFGGWTSASRKAMLPVFERYKNLLWYPVQFEGNEASPNIIYTGA

QPNQQILPALEWALKQGYK FFLVGSDYVFPRTANLILKKHIQKNGAIVS

GEEYWLGGTDFSAVVN IINTKPDIVFNTINGDSNVAFFKQMAAAGVGP

KVLPVISFSIAEQEAKAIGIPLLEGSYAAWNYFMSLNNKANLEFIKAYQG

KYGKSSLITDPMAHGYMNVYLWKMAVEKAGTFDPMMVRKAATELPWVDSP

FGKIKIAK QSLYQTAYIGKLGSDGQFSrV SSGKPIEPEPYDKLVFPGK

KAVLGGSHHHHHH* *

gkUBPIO (SEQ ID NO: 20)

M AEE SDNVD S AD AEEDD SD VWWGGADTD YADGSEDK WEVAEEEEVAE VE

EEEADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVLE

VLFQGPASSAVDQAKNTENK DSSSASKEGDTVKVGILHSLSGTMAISEVS

LRDAELMAmEINASGGLLGKKffiPWEDGASDWPTFAEKAKf LLQKDQV

AAIFGGWTSASRKAMLPWEQNNGLLWYPVQYEGMESSPNIFYTGATTNQ

QI AVSWLLKNRGKTFFLLGSDYVFPRTANKIIKAQLKAEGGQVVGEEY

TPLGHTDYSTIISKIKQVKPAWFNTLNGDSNVAFFKQLKDAGITPKDVT

VMSVSIAEEEIRGIGPDVLAGHLAVWNY QTTDTPENKAFVQKYKEKYGQ

DRVTDDPEAAYTAVHLWAEAVK AGSFDVDQVK AAAGLEYKAPEGTVK

IDGETQHLWKTVRIGEIQADGQFKELWNSGQPVKPDPYLKSYPWAKGLSE

GGSHHHHHHHH* *

psUBPl l (SEQ ID NO: 21)

M AEE SDNVD SAD AEEDD SD VWWGGADTD YADGSEDK WEVAEEEEVAE VE

EEEADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVLE

VLFQGPKETAPTAGAGNGSPPVEAAGDSn VGILHSLSGTMAISEVSVKD

AEMLAIEEINAAGGVLGKQIEPVIEDGASDWPTFAEKAGKLLQQDKVAAV

FGGWTSASRKAMLPVFEQNHGLLFYPVQYEGLESSPNIFYTGATTNQQIV

PSVSWLLENRGKKMFLLGSDYVFPRTANKIIKAQLTAEGGELAGEEYTPL

GHTDFSTIIAKIKEAKPDIVYNTLNGDSNVAFFKQLKDAGTTSKDMTTLS

VSVAEEEIRGIGADILEGHLAAWNYYQSTDTPENKAFVDKYKAKYGADRV

TADPIEAGYTAVYLWKAAVEKAGTTDVDKVKEAAKGIEFAAPEGKVTIDG

DNQHmKTVRIGEVQADGQFKELWNSGEPVKPDPYLKTYDWAKGLSGEGG

SHHHHHH**

teUBP12 (SEQ ID NO: 22)

M AEE SDNVD SAD AEEDD SD VWWGGADTD YADGSEDKWEVAEEEEVAEVE

EEEADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVLE

VLFQGPGGDTIKVGILHSLSGTMAISEKSWDATQLAIEQINQAGGVLGK

QIQPILEDGASDWPTFAEKATKLIDQDKWAVFGAWTSASRKAVLPVFES

KNHMLWYPVQYEGQEASKNIFYTGAAPNQQIEPAVDWLLQNKGKKFFLVG

SDYVFPRTANTIIKAQLAAKGGETVGEDYLPLGNTEVTPIITRIRNALPD

GGVIFNTLNGDSNVAFFKQLQGAGLTPDKYPTMSVSIAEEEVQAIGVEYL

KGHYAAWNY MTVDTPENKSFVEAFKAKFGQNRVTNDPMEAAYIAVHLWK

QAVEQAGTADDLEKVRQAAIGQTFNAPEGPVKMFANHHISKTVRIGEVGE Attorney Docket No. 35327-522001 WO

DGLFKIVYSTPQPVDPLPWNQFVAETKGFAADWTRTDVDNPGKFKAAGAG GSHHHHHH**

Cysteine Scans

csUBP7_26C (SEQ ID NO: 23)

MSSSESEKEKSEETIKVGILHSLSGCMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDY PRTANKIIKAYLKYLGGVVVGEEYTPLGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_27C (SEQ ID NO: 24)

MSSSESEKEKSEETIKVGILHSLSGTCSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDY PRTANKIKAYLKYLGGVVVGEEYTPLGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_30C (SEQ ID NO: 25)

MSSSESEKEKSEETIKVGILHSLSGTMSICEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVVVGEEYTPLGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_65C (SEQ ID NO: 26)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGACDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVVVGEEYTPLGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_69C (SEQ ID NO: 27)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG VLGK LEPIVEDGASDWPCFAEKAKKLLQKDKVAVIFGAWTSASRKAVLP VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPLGHTDYSSVINKIKA Attorney Docket No. 35327-522001 WO

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_90C (SEQ ID NO: 28)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGACTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDY PRTANKIKAYLKYLGGVVVGEEYTPLGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_91C (SEQ ID NO: 29)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWCSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVVVGEEYTPLGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_92C (SEQ ID NO: 30)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTCASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDY PRTANKIKAYLKYLGGV GEEYTPLGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_93C (SEQ ID NO: 31)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSCSRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVVVGEEYTPLGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_95C (SEQ ID NO: 32)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASCKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF Attorney Docket No. 35327-522001 WO

YLLGSDY PRTANKIKAYLKYLGGVVVGEEYTPLGHTDYSSVINKIKA AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_l 11C (SEQ ID NO: 33)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFCPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDY PRTANKIKAYLKYLGGVVVGEEYTPLGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_l 14C (SEQ ID NO: 34)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVCYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVVVGEEYTPLGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_l 15C (SEQ ID NO: 35)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQCEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVVVGEEYTPLGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_l 16C (SEQ ID NO: 36)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYCGLESSPNIFYMGAAPNQQIVPAVKWLFDNGKKRF

YLLGSDYVFPRTANKIIKAYLKYLGGVVVGEEYTPLGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_157C (SEQ ID NO: 37)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP Attorney Docket No. 35327-522001 WO

WEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGKKRF

YLLGSDC PRTANKIKAYLKYLGGV GEEYTPLGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_158C (SEQ ID NO: 38)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYCFPRTANKIKAYLKYLGGVVVGEEYTPLGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_159C (SEQ ID NO: 39)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVCPRTANKIKAYLKYLGGVWGEEYTPLGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIRELWKTNKPVKPDPYLKGYEWAQGLSEQGGSHHHHHH**

csUBP7_186C (SEQ ID NO: 40)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVVVGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_211C (SEQ ID NO: 41)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVVVGEEYTPLGHTDYSSVINKIKA

AKPDWFNTLCGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYKKKYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_238C (SEQ ID NO: 42)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG Attorney Docket No. 35327-522001 WO

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQI AVKWLFDNGKKRF

YLLGSDY PRTANKIKAYLKYLGGVVVGEEYTPLGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVCIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

bsUBP3_76C (SEQ ID NO: 43)

MKVGILHSLSGTMAISEVSVHDAELIAIQEINQKGGVLGK LEPWEDGA

SDWPTYAEKMRKLLQQDKVAAVFGGCTSASRKAMLPVVEQNNGLLFYPVQ

YEGMETSPNIFYTGATTNQQIVPAVDWLLKNKGK FFLIGSDYVFPRTAN

KIKAQVKAGGGEIAGEEYTPLGHTNYSTLVSKIKEKQPDVIFNTLNGDS

NVAFFKQLKDAGISADDMPVMSASVAEEEIRGIGPDVLKGHYAVWNYFQT

TNTSENQTFVKN^KECMNGDSRVTSDPIEAGYNAVYLWAAAVEKAKSFDVD

KVK AADGISFKAPGGTVKIDGDTQHLYKTVRIGQITGDGQFKEVWNSGE

P VKPDP YLKT YDWAKGLSKGGSHHHHHH* *

bsUBP3_77C (SEQ ID NO: 44)

MKVGILHSLSGTMAISEVSVHDAELIAIQEINQKGGVLGK LEPVVEDGA

SDWPTYAEKMRKLLQQDKVAAVFGGWCSASRKAMLPVVEQNNGLLFYPVQ

YEGMETSPNIFYTGATTNQQIVPAVDWLLKNKGK FFLIGSDYVFPRTAN

KIKAQVKAGGGEIAGEEYTPLGHTNYSTLVSKIKEKQPDVIFNTLNGDS

NVAFFKQLKDAGISADDMPVMSASVAEEEIRGIGPDVLKGHYAVWNYFQT

TNTSENQTFVKN^KKMNGDSRVTSDPIEAGYNAVYLWAAAVEKAKSFDVD

KVK AADGISFKAPGGTVKIDGDTQHLYKTVRIGQITGDGQFKEVWNSGE

P VKPDP YLKT YDWAKGLSKGGSHHHHHH* *

bsUBP3_78C (SEQ ID NO: 45)

MKVGILHSLSGTMAISEVSVHDAELIAIQEINQKGGVLGKKLEPWEDGA

SDWPTYAEKMR LLQQDKVAAVFGGWTCASRKAMLPVVEQNNGLLFYPVQ

YEGMETSPNIFYTGATTNQQI AVDWLLKNKGKKFFLIGSDYVFPRTAN

KIIKAQVKAGGGEIAGEEYTPLGHTNYSTLVSKIKEKQPDVIFNTLNGDS

NVAFFKQLKDAGISADDMPVMSASVAEEEIRGIGPDVLKGHYAVWNYFQT

TNTSENQTFVKNYKKMNGDSRVTSDPIEAGYNAVYLWAAAVEKAKSFDVD

KVKKAADGISFKAPGGTVKIDGDTQHLYKTVRIGQITGDGQFKEVWNSGE

P VKPDP YLKT YDWAKGLSKGGSHHHHHH* *

bsUBP3_79C (SEQ ID NO: 46)

MKVGILHSLSGTMAISEVSVHDAELIAIQEINQKGGVLGKKLEPWEDGA

SDWPTYAEKMRKLLQQDKVAAVFGGWTSCSRKAMLPVVEQNNGLLFYPVQ

YEGMETSPNIFYTGATTNQQIVPAVDWLLKNKGKKFFLIGSDYVFPRTAN

KIIKAQVKAGGGEIAGEEYTPLGHTNYSTLVSKIKEKQPDVIFNTLNGDS

NVAFFKQLKDAGISADDMPVMSASVAEEEIRGIGPDVLKGHYAVWNYFQT

TNTSENQTFVKNYKKMNGDSRVTSDPIEAGYNAVYLWAAAVEKAKSFDVD

KVKKAADGISFKAPGGTVKIDGDTQHLYKTVRIGQITGDGQFKEVWNSGE

P VKPDP YLKT YDWAKGLSKGGSHHHHHH* *

bsUBP3_145C (SEQ ID NO: 47) Attorney Docket No. 35327-522001 WO

MKVGILHSLSGTMAISEVSVHDAELIAIQEINQKGGVLGK LEPVVEDGA

SDWPTYAEKMR LLQQDKVAA GGW SASR AMLPVVEQNNGLLFYPVQ

YEGMETSPNIFYTGATTNQQIVPAVDWLLKN GK FFLIGSDYVCPRTAN

KIIKAQVKAGGGEIAGEEYTPLGHTNYSTLVSKIKEKQPDVIFNTLNGDS

NVAFFKQLKDAGISADDMPVMSASVAEEEIRGIGPDVLKGHYAVWNYFQT

TNTSENQTFVKN^KECMNGDSRVTSDPIEAGYNAVYLWAAAVEKAKSFDVD

KVK AADGISFKAPGGTVKIDGDTQHLYKTVRIGQITGDGQFKEVWNSGE

P VKPDPYLKTYDWAKGLSKGGSHHHHHH* *

bsUBP3_172C (SEQ ID NO: 48)

MKVGILHSLSGTMAISEVSVHDAELIAIQEINQKGGVLGK LEPWEDGA

SDWPTYAEKMRKLLQQDKVAAVFGGWTSASRKAMLPVVEQNNGLLFYPVQ

YEGMETSPNIFYTGATTNQQIVPAVDWLLKNKGK FFLIGSDYVFPRTAN

KIIKAQVKAGGGEIAGEEYTPCGHTNYSTLVSKIKEKQPDVIFNTLNGDS

NVAFFKQLKDAGISADDMPVMSASVAEEEIRGIGPDVLKGHYAVWNYFQT

TNTSENQTFVKN^KECMNGDSRVTSDPIEAGYNAVYLWAAAVEKAKSFDVD

KVK AADGISFKAPGGTVKIDGDTQHLYKTVRIGQITGDGQFKEVWNSGE

P VKPDPYLKTYDWAKGLSKGGSHHHHHH* *

ctUBP6_95C (SEQ ID NO: 49)

MVEEPVDNKPGTDTSAEDTIKVGILHSLSGTMAISEVSLKDAELMAIEEI

NQAGGLLGKKIEPVIEDGASDWPTFAEKAKKLLQNDKVATVFGCCTSASR

KAVLPVFEENNGLLWYPVQYEGMESSPNIFYTGAAPNQQIVPAVEWLLEN

KGKRFFLLGSDYVFPRTANKIIKAQLSAIGGELIAEEYTPLGHTDYSTIV

NKIKTAKPDWFNTLNGDSNVAFFKQLKDAGITSEDITVCSVSVAEEEIR

GIGAENIKGHLVSWNYYQTTDTPENKEFVEKYKSKYGSDRVTDDPIEAAY

IAVHLWAEAVKKAGSFEVEKVKEAAKGLEFKAPEGLVKIEGENQHLWKPV

RIGEVQEDGLKEIWSTSEAVRPDPYLKTYDWAKGLSDGGSHHHHHH**

ctUBP6_96C (SEQ ID NO: 50)

MVEEPVDNKPGTDTSAEDTIKVGILHSLSGTMAISEVSLKDAELMAIEEI

NQAGGLLGKKIEPVIEDGASDWPTFAEKAKKLLQNDKVATVFGCWCSASR

KAVLPVFEENNGLLWYPVQYEGMESSPNIFYTGAAPNQQIVPAVEWLLEN

KGKRFFLLGSDYVFPRTANKIIKAQLSAIGGELIAEEYTPLGHTDYSTIV

NKIKTAKPDWFNTLNGDSNVAFFKQLKDAGITSEDITVCSVSVAEEEIR

GIGAENIKGHLVSWNYYQTTDTPENKEFVEKYKSKYGSDRVTDDPIEAAY

IAVHLWAEAVKKAGSFEVEKVKEAAKGLEFKAPEGLVKIEGENQHLWKPV

RIGEVQEDGLKEIWSTSEAVRPDPYLKTYDWAKGLSDGGSHHHHHH**

ctUBP6_97C (SEQ ID NO: 51)

MVEEPVDNKPGTDTSAEDTIKVGILHSLSGTMAISEVSLKDAELMAIEEI

NQAGGLLGKKIEPVIEDGASDWPTFAEKAKKLLQNDKVATVFGCWTCASR

KAVLPVFEENNGLLWYPVQYEGMESSPNIFYTGAAPNQQIVPAVEWLLEN

KGKRFFLLGSDYVFPRTANKIIKAQLSAIGGELIAEEYTPLGHTDYSTIV

NKIKTAKPDWFNTLNGDSNVAFFKQLKDAGITSEDITVCSVSVAEEEIR

GIGAENIKGHLVSWNYYQTTDTPENKEFVEKYKSKYGSDRVTDDPIEAAY

IAVHLWAEAVKKAGSFEVEKVKEAAKGLEFKAPEGLVKIEGENQHLWKPV

RIGEVQEDGLKEIWSTSEAVRPDPYLKTYDWAKGLSDGGSHHHHHH** Attorney Docket No. 35327-522001 WO ctUBP6_98C (SEQ ID NO: 52)

MVEEPVDNKPGTDTSAEDTIKVGILHSLSGTMAISEVSLKDAELMAIEEI

NQAGGLLGK IEPVIEDGASDWPTFAEKAKKLLQNDKVATVFGCWTSCSR

KAVLPVFEENNGLLWYPVQYEGMESSPNIFYTGAAPNQQIVPAVEWLLEN

KGKRFFLLGSDYVFPRTANKIIKAQLSAIGGELIAEEYTPLGHTDYSTIV

NKIKTAKPDWFNTLNGDSNVAFFKQLKDAGITSEDITVCSVSVAEEEIR

GIGAENIKGHLVSWNYYQTTDTPENKEFVEKYKSKYGSDRVTDDPIEAAY

IAVHLWAEAVK AGSFEVEKVKEAAKGLEFKAPEGLVKIEGENQHLWKPV

RIGEVQEDGLKEIWSTSEAVRPDPYLKTYDWAKGLSDGGSHHHHHH**

ctUBP6_164C (SEQ ID NO: 53)

MVEEPVDNKPGTDTSAEDTIKVGILHSLSGTMAISEVSLKDAELMAIEEI

NQAGGLLGK IEPVIEDGASDWPTFAEKAKKLLQNDKVATVFGCWTSASR

KAVLPVFEENNGLLWYPVQYEGMESSPNIFYTGAAPNQQIVPAVEWLLEN

KGKRFFLLGSDYVCPRTANKIIKAQLSAIGGELIAEEYTPLGHTDYSTIV

NKIKTAKPDWFNTLNGDSNVAFFKQLKDAGITSEDITVCSVSVAEEEIR

GIGAENIKGHLVSWNYYQTTDTPENKEFVEKYKSKYGSDRVTDDPIEAAY

IAVHLWAEAVK AGSFEVEKVKEAAKGLEFKAPEGLVKIEGENQHLWKPV

RIGEVQEDGLKEIWSTSEAVRPDPYLKTYDWAKGLSDGGSHHHHHH**

ctUBP6_191C (SEQ ID NO: 54)

MVEEPVDNKPGTDTSAEDTIKVGILHSLSGTMAISEVSLKDAELMAIEEI

NQAGGLLGK IEPVIEDGASDWPTFAEKAKKLLQNDKVATVFGCWTSASR

KAVLPVFEENNGLLWYPVQYEGMESSPNIFYTGAAPNQQIVPAVEWLLEN

KGKRFFLLGSDYVFPRTANKIIKAQLSAIGGELIAEEYTPCGHTDYSTIV

NKIKTAKPDWFNTLNGDSNVAFFKQLKDAGITSEDITVCSVSVAEEEIR

GIGAENIKGHLVSWNYYQTTDTPENKEFVEKYKSKYGSDRVTDDPIEAAY

IAVHLWAEAVK AGSFEVEKVKEAAKGLEFKAPEGLVKIEGENQHLWKPV

RIGEVQEDGLKEIWSTSEAVRPDPYLKTYDWAKGLSDGGSHHHHHH**

csUBP7 186C Affinity Tuning

csUBP7_186C.l (SEQ ID NO: 55)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIQEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVVVGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVENYK MYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C.2 (SEQ ID NO: 56)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVVVGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTSDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI Attorney Docket No. 35327-522001 WO

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C3 (SEQ ID NO: 57)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDY PRTANKIIKAYLKYLGGVVVGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPGGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C4 (SEQ ID NO: 58)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

WEENNGLLFYPVQYQGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C5 (SEQ ID NO: 59)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYDGLESSPNIFYMGAAPNQQIVPAVKWLFDNGKKRF

YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C6 (SEQ ID NO: 60)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

WEENNGLLFYPVQYAGLESSPNIFYMGAAPNQQIVPAVKWLFDNGKKRF

YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C.7 (SEQ ID NO: 61)

MSSSESEKEKSEETIKVGILHSLSGTMSIIEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAAEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL Attorney Docket No. 35327-522001 WO

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI LENGQIREL WKTNKP V DPYLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C8 (SEQ ID NO: 62)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDY PRTANKIIKAYLKYLGGVVVGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLSGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C9 (SEQ ID NO: 63)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVSYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C10 (SEQ ID NO: 64)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVNYEGLESSPNIFYMGAAPNQQI AVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C.l 1 (SEQ ID NO: 65)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTAASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C12 (SEQ ID NO: 66)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFAPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE Attorney Docket No. 35327-522001 WO

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C13 (SEQ ID NO: 67)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDA PRTANKIKAYLKYLGGVVVGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C14 (SEQ ID NO: 68)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVAPRTANKIKAYLKYLGGVVVGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDPYLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C15 (SEQ ID NO: 69)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPAQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C16 (SEQ ID NO: 70)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

WEENNGLLFYPTQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGKKRF

YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C17 (SEQ ID NO: 71)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP VVEENNGLLFYPNQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA Attorney Docket No. 35327-522001 WO

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI LENGQIRELWKTNKPVKPDPYLKGYEWAQGLSEQGGSHHHHHH**

csUBP7_186C18 (SEQ ID NO: 72)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPQQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDY PRTANKIKAYLKYLGGVVVGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C19 (SEQ ID NO: 73)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPHQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYKKKYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C20 (SEQ ID NO: 74)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVAYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C21 (SEQ ID NO: 75)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVDYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDY PRTAN IKAYLKYLGGV GEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C.22 (SEQ ID NO: 76)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

WEENNGLLFYPVEYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGKKRF Attorney Docket No. 35327-522001 WO

YLLGSDY PRTANKIKAYLKYLGGVVVGEEYTPCGHTDYSSVINKIKA AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C.23 (SEQ ID NO: 77)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVHYEGLESSPNIFYMGAAPNQQI AVKWLFDNGK RF

YLLGSDY PRTANKIKAYLKYLGGVVVGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* * csUBP7_186C.24 (SEQ ID NO: 78)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVTYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* * csUBP7_186C.25 (SEQ ID NO: 79)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVYYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C26 (SEQ ID NO: 80)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVMYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C.27 (SEQ ID NO: 81)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP Attorney Docket No. 35327-522001 WO

WEENNGLLFYPVLYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGKKRF

YLLGSDY PRTANKIKAYLKYLGGVVVGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIRELWKTNKPVKPDPYLKGYEWAQGLSEQGGSHHHHHH**

csUBP7_186C28 (SEQ ID NO: 82)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDY PRTANKIKAYLKYLGGVVVGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLAGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C29 (SEQ ID NO: 83)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLQGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYKKKYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C30 (SEQ ID NO: 84)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLSGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C31 (SEQ ID NO: 85)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDY PRTAN IKAYLKYLGGV GEEYTPCGHTDYSSVINKIKA

AKPDWFNTLDGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C.32 (SEQ ID NO: 86)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG Attorney Docket No. 35327-522001 WO

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGKKRF

YLLGSDY PRTANKIKAYLKYLGGVVVGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLEGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C33 (SEQ ID NO: 87)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDY PRTANKIKAYLKYLGGVVVGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLHGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C34 (SEQ ID NO: 88)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

WEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLTGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C35 (SEQ ID NO: 89)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLLGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C36 (SEQ ID NO: 90)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVAIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C.37 (SEQ ID NO: 91) Attorney Docket No. 35327-522001 WO

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEIN NGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQI AVKWLFDNGKKRF

YLLGSDY PRTANKIKAYLKYLGGVVVGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVNIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKP VKPDPYLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C38 (SEQ ID NO: 92)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDY PRTANKIKAYLKYLGGVVVGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVQIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7_186C39 (SEQ ID NO: 93)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVHIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYKKKYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIREL WKTNKPVKPDP YLKGYEWAQGLSEQGGSHHHHHH* *

csUBP7 C-teiminal bZif Constructs

csUBP7_26C_bZif (SEQ ID NO: 94)

MSSSESEKEKSEETIKVGILHSLSGCMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVVVGEEYTPLGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIRELWKTNKPVKPDPYLKGYEWAQGLSEQGGSGGSTGEKPYKCPE

CGKSFSRSGGSHHHHHH* *

csUBP7_27C_bZif (SEQ ID NO: 95)

MSSSESEKEKSEETIKVGILHSLSGTCSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVVVGEEYTPLGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI Attorney Docket No. 35327-522001 WO

LENGQIRELWKTNKPVKPDPYLKGYEWAQGLSEQGGSGGSTGEKPYKCPE CGKSFSRSGGSHHHHHH* *

csUBP7_30C_bZif (SEQ ID NO: 96)

MSSSESEKEKSEETIKVGILHSLSGTMSICEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDY PRTANKIKAYLKYLGGV GEEYTPLGHTDYSSVIN IKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIRELWKTNKPVKPDPYLKGYEWAQGLSEQGGSGGSTGEKPYKCPE

CGKSFSRSGGSHHHHHH**

csUBP7_95C_bZif (SEQ ID NO: 97)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGKKLEPIVEDGASDWPTFAEKAKKLLQKDKVAVIFGAWTSASCKAVLP

VVEENNGLLFYPVQYEGLESSPNIFYMGAAPNQQI AVKWLFDNGKKRF

YLLGSDY PRTANKIIKAYLKYLGGVVVGEEYTPLGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYKKKYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIRELWKTNKPVKPDPYLKGYEWAQGLSEQGGSGGSTGEKPYKCPE

CGKSFSRSGGSHHHHHH**

csUBP7_186C.20_bZif (SEQ ID NO: 98)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGKKLEPIVEDGASDWPTFAEKAKKLLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVAYEGLESSPNIFYMGAAPNQQI AVKWLFDNGKKRF

YLLGSDY PRTANKIKAYLKYLGGVVVGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYKKKYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIRELWKTNKPVKPDPYLKGYEWAQGLSEQGGSGGSTGEKPYKCPE

CGKSFSRSGGSHHHHHH**

csUBP7 Immobilization Constructs

csUBP7_186C.l 14A_Imml (SEQ ID NO: 99)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGKKLEPIVEDGASDWPTFAEKAKKLLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVAYEGLESSPNIFYMGAAPNQQI AVKWLFDNGKKRF

YLLGSDY PRTANKIKAYLKYLGGVVVGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYKKKYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIRELWKTNKPVKPDPYLKGYEWAQGLSEQGGSKKKKKKGGSHHHH

HH**

csUBP7_186C.114A_Imm2 (SEQ ID NO: 100) Attorney Docket No. 35327-522001 WO

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEIN NGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASR AVLP

VVEENNGLLFYPVAYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGKKRF

YLLGSDY PRTANKIKAYLKYLGGVVVGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIRELWKTNKPVKPDPYLKGYEWAQGLSEQGGSHHHHHHGGSK E i

K **

csUBP7_186C.114A_Imm3 (SEQ ID NO: 101)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEIN NGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVAYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDY PRTANKIKAYLKYLGGVVVGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE

YLKGHLVTWNYFQSVDTPENKEFVEKYK KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI

LENGQIRELWKTNKPVKPDPYLKGYEWAQGLSEQGGSHHHHHHGGSK E i

KKKKKK**

csUBP7_186C.114A_Imm4 (SEQ ID NO: 102)

MK EC f KGGSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAI

EEI nWGGVLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTS

ASRKAVLPWEENNGLLFYPVAYEGLESSPNIFYMGAAPNQQIVPAVKWL

FDNGK RFYLLGSDYVFPRTANKIKAYLKYLGGVVVGEEYTPCGHTDYS

SVIN IKAAKPDVVFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEE

EIKGIGPEYLKGHLVTWNWQSVDTPENKEFVEKYK KYGEDRVTDDPIE

AAYIGVYLWAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLY

KTVRIGEILENGQIRELWKTNKPVKPDPYLKGYEWAQGLSEQGGSHHHHH

j _j ** csUBP7_186C.114A_Imm5 (SEQ ID NO: 103)

MK f f f fO Kf KGGSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAE

LMAffiEINNNGGVLGKKLEPIVEDGASDWPTFAEKAKKLLQKDKVAVIFG

AWTSASRKAVLPWEENNGLLFYPVAYEGLESSPNIFYMGAAPNQQIVPA

VKWLFDNGK RFYLLGSDYVFPRTANKIKAYLKYLGGVVVGEEYTPCGH

TDYSSVINKKAAKPDVVFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVS

LAEEED GIGPEYLKGHLVTWNYFQSVDTPENKEFVEKYKKKYGEDRVTD

DPIEAAYIGVYLWAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDN

QHLYKTVRIGEILENGQIRELWKTNKPVKPDPYLKGYEWAQGLSEQGGSH

HHHHH**

csUBP7_186C.114A_Imm6 (SEQ ID NO: 104)

MSSSESEKEKSEETIKVGILHSLSGTMSISEVSLKDAELMAIEEINNNGG

VLGK LEPIVEDGASDWPTFAEKAK LLQKDKVAVIFGAWTSASRKAVLP

VVEENNGLLFYPVAYEGLESSPNIFYMGAAPNQQIVPAVKWLFDNGK RF

YLLGSDYVFPRTANKIIKAYLKYLGGVWGEEYTPCGHTDYSSVINKIKA

AKPDWFNTLNGDSNVAFFKQLKDAGIDANTLPVMSVSIAEEEIKGIGPE Attorney Docket No. 35327-522001 WO

YLKGHLVTWNYFQSVDTPENKEFVEKYKf KYGEDRVTDDPIEAAYIGVYL

WAKAVEKAGSTDVDKVREAAKGIEFNAPEGPVKIDGDNQHLYKTVRIGEI LENGQIRELWKTNKPVKPDPYLKGYEWAQGLSEQGGSGGSTGEKPYKCPE CGKSFSRSDHLSRHQRTHQNKKGGSFfflFfflHH**

Examples are provided below to facilitate a more complete understanding of the invention. The following examples illustrate the exemplary modes of making and practicing the invention. However, the scope of the invention is not limited to specific embodiments disclosed in these Examples, which are for purposes of illustration only, since alternative methods can be utilized to obtain similar results.

EXAMPLE 1. EXEMPLARY FLUORESCENTLY RESPONSIVE SENSOR

ENGINEERING PHASES

The engineering of FRSs can be divided into six phases:

1. Binding protein discovery. A set of binding protein sequence homologs is identified.

Accurate assignment of their urea-binding function requires combining genomic contextual and three-dimensional protein structural information.

2. Experimental lead validation. Synthetic genes are constructed, which are optimized for heterologous expression in Escherichia coli of one or more predicted urea-binding protein sequences. The urea-binding properties and thermostabilities of the corresponding expressed, purified proteins are evaluated.

3. Determination of the three-dimensional structure of an analyte-binding protein.

High-resolution X-ray crystallography is used to determine the three-dimensional structure of a representative urea-binding protein identified in step 2. This structure is used for execution of the next two phases.

4. Engineering of fluorescent responses. Semisynthetic fluorescent conjugates of the experimentally validated leads are constructed by first attaching single fluorophores to single cysteine mutants. The effect of urea binding on the fluorescence emission properties of those conjugates is evaluated. The spectral properties of a subset of responsive fluorophores is improved using a double-labeling strategy in which a second fluorophore is site-specifically attached to a small domain fused to the N- or C-terminus to establish ngmFRET. Those singly or doubly labeled conjugates that evince strong, ratiometric responses are selected as FRSs for use in sensing applications. Attorney Docket No. 35327-522001 WO

5. Affinity tuning. Single or multiple mutations are introduced by site-directed

mutagenesis to alter the urea-binding affinities of urea-responsive FRSs. A set of FRS variants is selected from a collection of affinity-tuned FRSs that spans almost four orders of magnitude (from 60 μΜ to 180 mM), suitable for accurately measuring urea concentrations in clinical [e.g. (less than about 2 mM), within (about 2 mM to about 7 mM), or above (greater than about 7 mM) the normal range of human blood] or environmental {e.g., from 60 μΜ to 180 mM) samples.

6. Device integration. FRSs are immobilized in the sampling component of the

analytical device in a manner that preserves their fluorescent response and urea affinity. Long-term storage conditions are established.

EXAMPLE 2. SENSOR ENGINEERING PHASE 1: IDENTIFICATION OF A FAMILY OF PERIPLASMIC UREA-BINDING PROTEINS HOMOLOGS USING STRUCTURALLY ASSISTED FUNCTION EVALUATION

Accurately assigning function to sequence homologs is a challenging task, especially when the degree of identity with the seed sequence of known biological function is low (Todd, 2001, J. Mol. Biol, 307, 1113-1143; Tian, 2003, J. Mol. Biol, 333, 863-882), e.g., less than 60% identity as determined by BLAST having the following parameters: (1) Expect threshold is 10.0; (2) Gap cost is Existence: 11 and Extension: 1 ; (3) The Matrix employed is BLOSUM62; (4) The filter for low complexity regions is "on." The diversity of ligands recognized by the PBP superfamily make this task especially difficult, as evidenced by the observation that related members in a clade or family can recognize chemically quite distinct molecules (Cuneo, Beese and Hellinga, 2009, J Biol Chem, 284, 33217-23; Nanavati, 2006, Appl. Environ. Microbiol, 72, 1336-1345).

The use of protein three-dimensional structural information provides a particularly powerful method for the accurate assignment of function. For instance, enzyme functional assignments are improved greatly if a sequence selection filter based on conservation of catalytic residues identified from protein structures is included. Such catalytic residues comprise a subset of all the residues that contact an enzyme substrate or inhibitor. In the case of the PBPs, functional selection filters need be even more stringent and take into account all the protein-ligand contacts that encode the entire ligand-recognition surface. Accordingly, we have developed a structurally assisted functional evaluation (SAFE) method to identify Attorney Docket No. 35327-522001 WO

PBP sequence homologs with accurately predicted function. The SAFE homolog search method consists of five steps:

1. Sequence homolog set is collected using the BLAST sequence alignment tool

(Altschul et al., 1990, JMolBiol, 215, 403-10), starting with the sequence of a protein of known structure that encodes either the desired, or a closely related function. The following BLAST parameters: (1) Expect threshold is 10.0; (2) Gap cost is

Existence: 11 and Extension: 1; (3) The Matrix employed is BLOSUM62; (4) The filter for low complexity regions is "on." Permissive settings are used, such that pairwise hits are required to have a minimum of only 20-25% sequence identity with the seed sequence. The lengths of the hit and seed are mutually constrained such that the alignment covers at least 70% within each partner. This set of sequences defines possible analyte-binding proteins without accurately assigning function.

2. Structure-based encoding of biological function. A primary complementary surface comprising the protein residues that form hydrogen bonds and van der Waals contacts with the bound analyte or related analyte-related molecule is defined using computer- assisted, visual inspection of the three-dimensional structure. This definition specifies residue positions and their permitted amino acid identity. Multiple amino acid identities are permitted at each position to encode functionally equivalent residues. This definition establishes a search filter for the accurate prediction of analyte-binding proteins within the universe of sequence homologs collected in Step (1).

3. Accurate sequence alignment. Tools such as ClustalW (Chenna et al., 2003, Nucleic Acids Res, 31, 3497-500) are used to construct an accurate alignment of all the sequence homologs. The structurally defined seed sequence is included in this alignment. This multiple sequence alignment establishes the equivalent residue positions of the PCS in each sequence homolog.

4. Function evaluation. The analyte-binding properties of each of the aligned sequence homologs is predicted by measuring their compliance of amino acid residue identity at each position within the PCS filter. A "Hamming distance", H, is assigned for each homolog, which specifies the degree of sequence identity of all the residues at the aligned PCS positions. A value of H=0 indicates that the identities of all the residues at the aligned PCS positions match the amino acid(s) allowed in the PCS search filter; H>0, indicates that one or more aligned positions have disallowed residues.

Sequences for which H=0 are predicted to encode analyte-binding proteins. Attorney Docket No. 35327-522001 WO

5. Selection of representative SAFE homologs. The sequence homologs are ordered by (a) identity with the seed PCS, as measured by the Hamming distance, (b) fractional overall sequence identity with the seed sequence. A subset for sequences with H=0, sampling the fractional overall sequence identity is selected for experimental verification.

These steps are encoded in the ProteinHunter software tool, which encodes the flow of execution, applies the PCS search filter, and visualizes the results, and handles organism annotations such as thermophilicity, and Gram stain status.

The ProteinHunter package always executes BLAST searches, with the following command

"blastall -p blastp -m 8 -b 50000 -d %s -i <INPUT FILE> -o OUTPUT FILE>" where <INPUT FILE> and OUTPUT FILE> specify the input and output files, respectively for a given calculation. This command executes the BLAST alignment program for protein sequences with default parameters, intrinsically set by the program. The BLAST program version is 2.2.24.

The ProteinHunter package always executes multiple sequence alignments with the following command

"clustalw -infile=<INPUT FILE> -outfile=OUTPUTFILE> -align -quiet"

This command executes the CLUSTALW multi-sequence alignment program for protein sequences. There are no user-specified parameter settings that alter the alignment behavior of the program. The CLUSTALW program version is 2.1.

Prior to the work reported here, no periplasmic urea-binding proteins (UBPs) had been characterized structurally. Accordingly, before we could apply the SAFE search procedure, we had to use experimentally verified UBP sequences to identify a structurally defined sequence homolog that binds a related ligand. Operons encoding ABC transporter systems for urea (urtABCDE) have been genotypically and phenotypically identified in

Anabaena sp. (avUBP), Synechocystis sp. (spUBP), and Corynebacterium glutamicum

(cgUBP). The sequence of their soluble periplasmic-binding component (urtA) was used to identify homologs in the Protein Databank, using the 'ProteinHunter' software package (A. variabilis sequence taken from GenBank genome sequence NC 007413, protein ID

YP 324854.1; C. glutamicum: genome NC 022040, protein YP 008401061.1). This search strategy identified a moderate degree of sequence homology with the Pseudomonas Attorney Docket No. 35327-522001 WO aeruginosa AmiC negative regulator of the amiEBCDRS amidase operon (paAmiC, PDB accession, lpea): avUBP, 31.8% identity; cgUBP, 29.8% identity. The structure of the paAmiC acetamide complex defines a PCS filter for acetamide, a ligand that is closely related to urea (FIGS. 2A and B, 3 and Table 1). The sequence of paAmiC is as follows:

MGSHQERPLIGLLFSETGVTADIERSQRYGALLAVEQLNREGGVGGRPIETLSQDPG G DPDRYRLCAEDFIRNRGVRFLVGCYMSHTRKAVMPWERADALLCYPTPYEGFEYS PNIVYGGPAPNQNSAPLAAYLIRHYGERVVFIGSDYIYPRESNHVMRHLYRQHGGTV LEEIYIPLYP SDDDLQRAVERIYQ ARADWF ST WGTGT AELYRAIARRYGDGRRPPI ASLTTSEAEVAKMESDVAEGQVWAPYFSSIDTPASRAFVQACHGFFPENATITAWA EAAYWQTLLLGRAAQAAGNWRVEDVQRHLYDIDIDAPQGPVRVERQNNHSRLSSRI AEIDARGVFQVRWQSPEPIRPDPYWVHNLDDWSASMGGGPLP (SEQ ID NO: 202)

The sequence of avUBP is as follows:

MSRRINRRRFLIYGSATIGSSILLKACANNTPNATNSPSTSGNASPVAASGGNTIKIGIL

HSLSGTMSISEKSVYDAEKLAKEINAAGGVLGKQIEAIVEDGASNWDTFREKATKLI

DQDKVAV GCWTSASRKNVKPVFESKDHMLWYPVQYEGQECSKNIFYTGAAPNQ

QIEPSVDWLLKNKGKEFFLVGSDYVFPRTANTHKAQLEALGGKTVGEDYLPLGNTE

VTPIITKIKQTLPNGGVIYNTLNGDSNVAFFKQLKGAGLTPDKYPSMSVSIAEEEVK AI

GVEYLKGHYAAWWFQT ^TPANKXFVEAFKKEYGADRVT^PMEAAYLAVYLW

KQAVEKAGSPDLAKVRAAAYGQTIDAPEGKVTVNANHHISKWRIGEVRDDGLFDI

VYATPAPVEPVPWNQFVKETKGFACDWSDPAKGGKYK A (SEQ ID NO: 226)

The sequence of cgUBP is as follows:

MSRPIVKQAFTVTAVTAMAFALASCTRAVDATSADGTASNTAASCVDTSGDSIKIGF

INSLSGTMAISETTVNQSLHMAADEINAAGGVLGKQLEISEEDGASEPATFAERSQR LI

QQECVAAVFGGWTSASRKAMLPVFEGNNSLLFYPVQYEGMESSPNIFYTGATTNQQ

IIPALDYLRENGLNRLFLVGSDYVFPRTANSIIKDYAEANGMEIVGEDYAPLGSTDF TT

IANRMRDSNADAVFNTLNGDSNVAFFRQYNSLGFNADTLPVMSVSIAEEEVGGIGTA

NmGQLVAWDYYQTIDTPENETFVENFKDLYGQDKVTSDPMEAAYTSLYLWKEMV

EKADSFDVAAIQAAADGTTFDAPEGTVWDGDNHHISKTPRIGRIRPDGLIDTIWETD

SPVDPDP YLS S YDWAKTTA

ATS (SEQ ID NO: 227) Attorney Docket No. 35327-522001 WO

Table 1. Residues that form the primary complementary surface in paAmiC and in the putative UreaBP PCS filter.

Next, we needed to establish the likely PCS filter that encodes recognition of urea instead of acetamide. To achieve this objective, genomic contextual information was used to identify a subset of sequences homologous to paAmiC, which that are likely to encode urea— rather than acetamide— binding proteins. To deduce a likely urea-binding PCS using information from this subset, we examined the identity of the PCS residues within its members.

As a first step in this procedure, the paAmiC sequence was used to identify a set of sequence homologs with at least 25% residue identity within a database of complete prokaryotic genome sequences. The database was constructed from the annotated genomic and plasmid sequences of 5062 prokaryotes obtained from the National Center of

Biotechnology Information (ftp://ftp.ncbi.nih.gov/genomes/Bacteria/all.gbk.tar.gz). The protein sequence for paAmiC was extracted from the protein structure file lpea (Pearl 1994 EMBO J., 13, 5810-5817; O'Hara 1999 EMBO J., 18, 5175-5186) and used as the seed sequence for the BLAST search described above (Table 2, line 1). We also constructed homolog sets for avUBP and cgUBP, using a minimum of 25% identity threshold (Table 2, lines 2 and 3). We then constructed a set comprising the intersection of the paAmiC, avUBP, and cgUBP homolog families (Table 2, line 4). This 'combined set' is intended to enrich for UBPs by ruling out sequences that cannot be identified by all three seeds. Attorney Docket No. 35327-522001 WO

Table 2. Operon linkage relationships".

"Operons are defined as contiguous strings of open reading frames located on the same DNA strand, each with an inter-genic distances of <100 bp. Homology families are defined for each of the individual components (lines 1-19) according to the BLAST search criteria defined in the footnotes. Homology families also can be constructed as intersections of multiple searches for a given component (e.g. lpean avn cg, line 4, is the set of hits common to the searches of lines 1-3). Noperon gives the number of hits that satisfy the operon combination rules (for single components, lines 1-19, it defines the size of the homology family; for ABC transporters, lines 20-22, it defines the number of operons that contain both ATPases and Permeases, etc.). The two PCS columns provide information on the diversity of the PCS sequences defined for paAmiC (lpea). Nu is the number of unique PCS sequences. π is the average diversity of the PCS sequences, calculated as follows. At each PCS position, i, the residue entropy is calculated:

aa

wheret _o is the frequency of amino acid aa (including indels, for a total of 21 choices) at that position. The maximum entropy is know: it is the entropy at which all amino acids (and indel) occur with equal probability: Attorney Docket No. 35327-522001 WO

J™ =-T— In— = ln 21 « 3.044

tf 21 21

We therefore can define a normalized entropy, or "diversity", at each position:

^S max

Si varies from 0 (no diversity) to 1 (random). For a PCS sequence comprising n residues, we define an averaged diversity

1 "

n w

bProbe is sequence from PDB accession lpea; minimum allowed fraction of identical residues f _m \ _n =025

^c variabilis genomic sequence NC 007413, protein identifier

mPDB accession \eil,f^=035.

Next we used genomic contextual information to identify the subset of homologs that are likely to have urea- rather than acetamide-binding properties by exploiting the observation that in prokaryotes related functions frequently are organized into operons (Osbourn, 2009, Cell. Mol. Life Set, 66, 3755-3775; Overbeek et al., 1999, Proc Natl Acad Sci USA, 96, 2896-901). PBPs often are components of multi-component ABC transporter systems arranged in operons. Both avUBP and gsUBP are located in operons that also contain the permease and ATPase heterodimers of the ABC transporter components for urea uptake (FIG. 4). If any of these polycistronically linked components encode specificity for urea, linkage relationships between their homologs and the AmiC homologs may identify subsets of the latter that are specific for urea. We therefore constructed homology families for the ATPase and permease heterodimers taken from A. variabilis (ATPase subunits seeds: NC_007413|YP_324857.1, NC_007413|YP_324858.1; permease subunits seeds:

NC_007413|YP_324855.1, NC_007413|YP_324856.1) and C. glutamicum (ATPase subunits seeds: NC_022040|YP_008401064.1, NC_022040|YP_008401065.1 ; permease subunits seeds: NC_022040|YP_008401062.1, NC_022040|YP_008401063.1), using 35% minimum identity threshold (Table 2, lines 5-9). Attorney Docket No. 35327-522001 WO

Functional constraints are expected to manifest themselves as a lessening in the sequence diversity of the PCS and the number of hits in the paAmiC homology family.

These effects were clearly observed in the various combinations of the components (Table 3). The combined set comprising the intersection of the paAmiC, avUBP, and cgUBP homology families restrained the PCS diversity (Table 2, line 4). Various operons linkages were constructed using the OntologyMgr' and 'Linkage Viewer' programs. Linkage of the combined set with all four transporter components (Table 2, lines 23-25) resulted in the emergence of dominant sequences, which are two nearly identical sequences in the most conservatively selected set of components (line 25).

Attorney Docket No. 35327-522001 WO

Table 3. PCS sequences in selected operon combinations.

'See Table 2.

bCompared against the wild-type paAmiC. Only differences are shown. The dominant sequences are shown in bold italic,

frequency of sequence in the set. Attorney Docket No. 35327-522001 WO

We also examined the linkage relationship between the paAmiC homologs and urease a subunit homologs. The hydrolysis of urea into bicarbonate and ammonia by urease can be regarded as the first committed step in urea catabolism. Metabolite uptake and first committed steps also are often combined into operons. A urease homolog set was constructed using the Klebsiella aerogenes urease as a seed, extracted from the PDb entry lef2 (Yamaguchi et al., 1999, J Biol Inorg Chem, 4, 468-77). A 30% identity minimum threshold was used (Table 2, line 18). Operons that combine the urease a subunit and paAmiC homolog sets yielded the same dominant PCS sequence as was identified in the operons based on ABC transporter membrane components.

These two analyses of the contextual genomic information identified a PCS sequence that is predicted to define urea-binding proteins within the paAmiC homolog set (Table 1). This PCS replaces three hydrophobic residues that surround the acetamide methyl group with residues that could function as multiple hydrogen-bond acceptors consistent with the conversion of the methyl group into an amine.

The putative urea-binding PCS was used to identify UBP candidates in the paAmiC homology family. Of the 905 members, 481 were predicted to be UBPs with overall homologies ranging from 51% to 24% sequence identity (FIG. 5A). Several of these hits were identified in thermophilic bacteria, and are correspondingly thermostable (T _m values > 60°C), which is advantageous in the construction of robust biosensors.

EXAMPLE 3. SENSOR ENGINEERING PHASE 2: LEAD PROTEIN VALIDATION USING LIGAND-MEDIATED THERMOSTABILITY SHIFTS

Eleven homologs that were predicted to be urea-binding proteins (Fig. 6) were selected to probe different degrees of sequence identity to the paAmiC (PDB accession, lpea) seed, and to identify UBPs in thermophilic bacteria. The urea-binding properties of these leads were determined experimentally (Table 4). These experiments comprise four successive steps:

1. Synthetic gene construction. The amino acid sequence of the homology leads were backtranslated into DNA sequences. These were optimized for directing heterologous cytoplasmic expression of the protein homologues in E. coli, using the OrfOpt program (U.S. Patent Publication No. 2011/0171737, hereby incorporated by reference). This program predicts mRNA sequences that direct high-level protein Attorney Docket No. 35327-522001 WO expression in E. coli. The predicted gene sequences were assembled de novo from synthetic oligonucleotides.

2. Heterologous protein expression of the homologues in E. coli. Plasmids carrying the synthetic expression constructs (see above) were transformed into KRX (E. coli K12 derivative strain) competent cells (Promega, Technical Bulletin TB352). Protein production was induced in bacterial cultures of these cultures.

3. Purification of successfully expressed protein using immobilized metal affinity

chromatography.

4. Verification of urea binding. Determination of the urea-binding properties of the purified proteins using a thermal stability shift assay.

Secretion of PBPs into the periplasm is directed by leader peptide sequences

(Eitinger, 2011, FEMS Microbiol. Rev., 35, 3-67). This leader sequence is usually removed in PBP expression constructs, so that the soluble form of the mature protein is produced in the cytoplasm. Alignment of the eleven sequences clearly indicates the start of the mature polypeptide (Fig. 6). Nevertheless, we explored a number of different starting points in the expression constructs. In all constructs we terminated the sequence with a hexahistidine tag to facilitate protein purification. In constructs for gkUBPlO, psUBPl 1, and tsUBP12 we also fused a Flag-acidic-target-tag (FATT) hyperacidic region (FATT domain) to the N-terminus (Sangawa et al. 2013 Protein Sci, 22, 840-50), which has been shown to significantly enhance proper folding of expressed proteins (Wood, 2014, Curr Opin Struct Biol, 26, 54-61).

Seven of the eleven leads (including all three FATT fusions), produced soluble protein in a T7 expression system in sufficient quantity for functional analysis. The urea- binding properties of all seven were confirmed directly using the thermal shift assay (Table 4)·

Attorney Docket No. 35327-522001 WO

Table 4. Li and-bindin and thermostabilit pro erties of UBP candidates.

"Number of identical residues shared with the paAmiC probe sequence.

bJudged by SDS gel electrophoresis of the soluble fraction of a total lysate.

determined in a Roche LightCycler, using SYPRO Orange to monitor the appearance of unfolded protein.

dDetermined by monitoring an increase in the thermostability of the protein in the presence of ligand. nd, not determined; too thermostable to determine.

Enfolded at room temperature in the absence of urea.

Attorney Docket No. 35327-522001 WO

EXAMPLE 4. SENSOR ENGINEERING PHASE 3: DETERMINATION OF csUBP7 STRUCTURE

The crystal structure of Caldicellusiruptor saccharolyticus urea-binding protein (csUBP7) was determined by high-resolution X-ray crystallography (Table 5). The overall structure is similar to paAmiC, superimposing with a backbone RMSD of 1.0 A (FIG. 7). The automatically assigned secondary structure elements are largely conserved (FIG. 8), although there are some subtle differences in their boundaries. Furthermore, csUBP7 a helix 8 is replaced by a less regular region in paAmiC; similarly β strand 11 in csUBP7 is not present in paAmiC.

Table 5. X-ray structure determination of csUBP7

Values for highest resolution shell are given in parentheses. Attorney Docket No. 35327-522001 WO

The structure of the csUBP7 urea complex (FIG. 7B) confirmes the accuracy of the urea- binding PCS deduced from the bioinformatics analysis described above. In many planar ligands bound by PBPs, both ligand faces form extensive van der Waals interactions with the protein, often by stacking against the rings of aromatic amino acids. In paAmiC one face of the acetamide stacks against a tyrosine, whereas the opposing forms less extensive van der Waals interactions with a threonine. Both types of interactions are retained in csUBP7, with the aromatic interaction contributed by F 159 (Yl 52 in paAmiC), and the opposing face by VI 13 (T106 in paAmiC).

The hydrogen-bonding potential of acetamide and urea are fully satisfied in both complexes. The donor hydrogen bonds to the carbonyl by tyrosine, and serine hydroxyl protons are retained. The amine group that is common to both acetamide and urea is bound by a single hydrogen bond acceptor, contributed by a tyrosine hydroxyl oxygen in both proteins. Remarkably, the hydrophobic surface that contacts the methyl group in paAmiC is replaced by three hydrogen bond acceptors, all of which interact with the second amine group in urea. In addition to contributing to the affinity of the interaction, this redundancy of interactions may confer specificity by selecting against groups that cannot form these hydrogen bonds.

The csUBP7 structure was used to aid in the identification of mutations that convert csUBP7 into a fiuorescently responsive urea sensors tuned to respond optimally in the clinically relevant urea concentration range (sensor engineering phases 4 and 5). It was also used to execute a SAFE search for UBP homologs, using the csUBP7 sequence as the seed, its PCS as the structure-based filter for function, and a more aggressive minimum identity threshold of 15%. The resulting set contains a total of 4732 sequences, of which 351 are predicted to be urea-binding proteins, based on their PCS Hamming score (H=0). Unlike the UBPs in this subset (Table 6) that are more closely related to the seed (identity varies from 100% to 43%) than is the case for the paAmiC set (compare FIGS. 5A and B). Attorney Docket No. 35327-522001 WO

Table 6. Urea-Binding Proteins

PCS position and sequence

Gram

# Accession 92 111 113 114 157 159 211 238 Identity Organism Temperature stain

1 csUBP7 (seed structure) S Y V Q Y F N S

2 NC_0094371 YP_001181243.1 S Y V Q Y F N S 0.99 Caldicellulosiruptor saccharol Thermophilic +

Desulfotomaculum

3 NC_0155651 YP_004496535.1 s Y V Q Y F N s 0.79 carboxydivora Mesophilic +

4 NC_015660|YP_004588319.1 s Y V Q Y F N s 0.78 Geobacillus thermoglucosidosiu Hyperthermophilic +

5 NC_014650|YP_003989571.1 s Y V Q Y F N s 0.78 Geobacillus sp. Thermophilic +

6 NC_009012 |Cthe_1823 s Y V Q Y F N s 0.78 Ruminiclostridium thermocellum Mesophilic +

7 NC_006510|YP_147790.1 s Y V Q Y F N s 0.77 Geobacillus kaustophilus Thermophilic +

8 NC_0149151 YP_004132472.1 s Y V Q Y F N s 0.77 Geobacillus sp. Thermophilic +

9 NC_0198971 YP_007214722.1 s Y V Q Y F N s 0.77 Thermobacillus composti Mesophilic +

10 NC_0151721 YP_004266518.1 s Y V Q Y F N s 0.76 Syntrophobotulus glycolicus Mesophilic -

11 NC_017672 | B2K_05545 s Y V Q Y F N s 0.74 Paenibacillus mucilaginosus Mesophilic +

12 NC_013406|YP_003241723.1 s Y V Q Y F N s 0.74 Paenibacillus sp. Mesophilic +

13 NC_0129141 YP_003009323.1 s Y V Q Y F N s 0.74 Paenibacillus sp. Mesophilic +

14 NC_0177431 YP_006233530.1 s Y V Q Y F N s 0.73 Bacillus sp. Mesophilic +

15 NC_0160471 YP_004879238.1 s Y V Q Y F N s 0.72 Bacillus subtilis Mesophilic +

16 NC_0156811 YP_004625975.1 s Y V Q Y F N s 0.71 Thermodesulfatator indicus Thermophilic -

17 NC_0101621 YP_001616222.1 s Y V Q Y F N s 0.71 Sorangium cellulosum Mesophilic -

18 NC_021658|SCE1572_33595 s Y V Q Y F N s 0.7 Sorangium cellulosum Mesophilic -

19 NC_017079|YP_005440252.1 s Y V Q Y F N s 0.7 Caldilinea aerophila Mesophilic +

20 NC_002570| NP_241117.1 s Y V Q Y F N s 0.69 Bacillus halodurans Mesophilic +

21 NC_022657 |AFR_30995 s Y V Q Y F N s 0.67 Actinoplanes friuliensis Mesophilic +

22 NC_0145011 YP_003886632.1 s Y V Q Y F N s 0.66 Cyanothece sp. Mesophilic -

23 NC_013510|YP_003300817.1 s Y V Q Y F N s 0.65 Thermomonospora curvata Thermophilic +

24 NC_0146661 YP_004018654.1 s Y V Q Y F N s 0.65 Frankia sp. Mesophilic +

25 NC_019729|YP_007118759.1 s Y V Q Y F N s 0.65 Oscillatoria igro-viridis Mesophilic +

26 NC_0130931 YP_003099469.1 s Y V Q Y F N s 0.65 Actinosynnema mirum Mesophilic +

27 NC_013739|YP_003395291.1 s Y V Q Y F N s 0.65 Conexibacter woesei Mesophilic +

28 NC_020990|YP_007744365.1 s Y V Q Y F N s 0.64 Streptomyces albus Mesophilic +

29 NC_011729|YP_002378135.1 s Y V Q Y F N s 0.64 Cyanothece sp. Mesophilic -

30 NC_019729|YP_007114178.1 s Y V Q Y F N s 0.64 Oscillatoria nigro-viridis Mesophilic +

31 NC_019738|YP_007121944.1 s Y V Q Y F N s 0.64 Microcoleus sp. Mesophilic +

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32 NC_010296|YP_001655636.1 S Y V Q Y 1 N S 0.64 Microcystis aeruginosa Mesophilic -

33 NC_0196831 YP_007069535.1 S Y V Q Y 1 N S 0.64 Leptolyngbya sp. Mesophilic +

34 NC_0041131 NP_681910.1 S Y V Q Y 1 N S 0.64 Thermosynechococcus elongatus Thermophilic +

35 NC_019689|YP_007081161.1 S Y V Q Y 1 N S 0.64 Pleurocapsa sp. Mesophilic +

36 NC_0031551 NP_822365.1 S Y V Q Y 1 N S 0.63 Streptomyces avermitilis Mesophilic +

37 NC_023033 | NK55_00205 S Y V Q Y 1 N S 0.63 Thermosynechococcus sp. Mesophilic +

38 NC_0197531 YP_007142922.1 S Y V Q Y 1 N S 0.63 Crinalium epipsammum Mesophilic +

39 NC_011884|YP_002482982.1 S Y V Q Y 1 N S 0.63 Cyanothece sp. Mesophilic -

40 NC_0197031 YP_007109005.1 S Y V Q Y 1 N S 0.63 Geitlerinema sp. Mesophilic +

41 NC_0032721 NP_485991.1 S Y V Q Y 1 N S 0.63 Nostoc sp. Mesophilic -

42 NC_020504|YP_007518655.1 S Y V Q Y 1 N S 0.63 Streptomyces davawensis Mesophilic +

43 NC_0074131 YP_324854.1 S Y V Q Y 1 N S 0.63 Anabaena variabilis Mesophilic +

44 NC_0196931 YP_007086905.1 S Y V Q Y 1 N S 0.63 Oscillatoria acuminata Mesophilic +

45 NC_0196931 YP_007086071.1 S Y V Q Y 1 N S 0.63 Oscillatoria acuminata Mesophilic +

46 NC_010628|YP_001867917.1 S Y V Q Y 1 N S 0.62 Nostoc punctiforme Mesophilic -

47 NC_019748|YP_007131516.1 S Y V Q Y 1 N S 0.62 Stanieria cyanosphaera Mesophilic +

48 NC_019776|YP_007163269.1 S Y V Q Y 1 N S 0.62 Cyanobacterium aponinum Mesophilic +

49 NC_0077751 YP_475333.1 S Y V Q Y 1 N S 0.62 Synechococcus sp. Thermophilic -

50 NC_017039|YP_005386846.1 S Y V Q Y 1 N S 0.62 Synechocystis sp. Mesophilic -

51 NC_0099251 YP_001515222.1 S Y V Q Y 1 N S 0.62 Acaryochloris marina Mesophilic -

52 NC_021177 |SFUL_1229 S Y V Q Y 1 N S 0.62 Streptomyces fulvissimus Mesophilic +

53 NC_0104751 YP_001733664.1 S Y V Q Y 1 N S 0.61 Synechococcus sp. Thermophilic -

54 NC_0170521 YP_005409553.1 S Y V Q Y 1 N S 0.61 Synechocystis sp. Mesophilic -

55 NC_0083121 YP_720098.1 s Y V Q Y 1 N S 0.61 Trichodesmium erythraeum Mesophilic -

56 NC_019778|YP_007164862.1 s Y V Q Y 1 N S 0.61 Cyanobacterium stanieri Mesophilic +

57 NC_0154341 YP_004406200.1 s Y V Q Y 1 N S 0.61 Verrucosispora maris Mesophilic +

58 NC_0196951 YP_007092842.1 s Y V Q Y 1 N s 0.61 Chroococcidiopsis thermalis Mesophilic +

59 NC_008820|YP_001018969.1 s Y 1 Q Y 1 N s 0.6 Prochlorococcus marinus Mesophilic -

60 NC_0197451 YP_007126262.1 s Y V Q Y 1 N s 0.6 Gloeocapsa sp. Mesophilic +

61 NC_0146591 YP_004008499.1 s Y V Q Y 1 N s 0.6 Rhodococcus equi Mesophilic +

62 NC_0197011 YP_007103966.1 s Y V Q Y 1 N s 0.6 Pseudanabaena sp. Mesophilic +

63 NC_020506|YP_007530234.1 s Y V Q Y 1 N s 0.6 Corynebacterium callunae Mesophilic +

64 NC_0050711 NP_896053.1 s Y 1 Q Y 1 N s 0.6 Prochlorococcus marinus Mesophilic -

65 NC_023150|Y013_09785 s Y V Q Y 1 N s 0.6 Rhodococcus pyridinivorans Mesophilic +

66 NC_015564|YP_004491855.1 s Y V Q Y 1 N s 0.6 Amycolicicoccus subflavus Mesophilic +

67 NC_0085961 MSMEG_2982 s Y V Q Y 1 N s 0.59 Mycobacterium smegmatis Mesophilic +

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68 NC_0043691 NP_737610.1 S Y V Q Y F N S 0.59 Corynebacterium efficiens Mesop ilic +

69 NC_0197021 YP_007104586.1 S Y V Q Y F N S 0.59 Synechococcus sp. Thermophilic -

70 NC_018581 | KTR9_3419 S Y V Q Y F N S 0.59 Gordonio sp. Mesophilic +

71 NC_023036| D174_12625 S Y V Q Y F N S 0.59 Mycobacterium neoaurum Mesophilic +

72 NC_016640|YP_005072561.1 S Y V Q Y F N S 0.59 Arthrospira platensis Mesophilic -

73 NC_0081461 YP_639455.1 S Y V Q Y F N S 0.59 Mycobacterium sp. Mesophilic +

74 NC_008726|YP_953410.1 S Y V Q Y F N S 0.59 Mycobacterium vanbaalenii Mesophilic +

75 NC_014814|YP_004077591.1 S Y V Q Y F N S 0.59 Mycobacterium gilvum Mesophilic +

76 NC_016604|YP_005003135.1 S Y V Q Y F N S 0.59 Mycobacterium rhodesiae Mesophilic +

77 NC_022115 |O5Y_07415 S Y V Q Y F N S 0.59 Rhodococcus erythropolis Mesophilic +

78 NC_0213511 YP_008065815.1 S Y V Q Y F N S 0.58 Corynebacterium glutamicum Mesophilic +

79 NC_003450| NCgl0893 S Y V Q Y F N S 0.58 OF INDUSTRIAL Mesophilic +

80 NC_0141511 YP_003635811.1 S Y V Q Y F N S 0.58 Cellulomonasflavigena Mesophilic +

81 NC_0180271 YP_006452781.1 S Y V Q Y F N S 0.58 Mycobacterium chubuense Mesophilic +

82 NC_0168871 YP_005266451.1 S Y V Q Y F N S 0.58 Nocardia cyriacigeorgica Mesophilic +

83 NC_0094821 YP_001228710.1 S Y 1 Q Y F N S 0.58 Synechococcus sp. Thermophilic -

84 NC_012522 |YP_002779037.1 S Y V Q Y F N S 0.58 Rhodococcus opacus Mesophilic +

85 NC_008268|YP_702091.1 S Y V Q Y F N S 0.58 Rhodococcus jostii Mesophilic +

86 NC_0063611 YP_121470.1 S Y V Q Y F N s 0.58 Nocardia farcin ica Mesophilic +

87 NC_0196751 YP_007046986.1 S Y 1 Q Y N s 0.58 Cyanobium gracile Mesophilic +

88 NC_0196821 YP_007067425.1 s Y V Q Y F N s 0.58 Calothrix sp. Mesophilic +

89 NC_011593 | Blon_0104 s Y L Q Y F N s 0.58 Bifidobacterium longum Mesophilic +

90 NC_007516|YP_382900.1 s Y 1 Q Y N s 0.57 Synechococcus sp. Thermophilic -

91 NC_008819|YP_001015739.1 s Y 1 Q Y F N s 0.57 Prochlorococcus marinus Mesophilic -

92 NC_009439|YP_001186201.1 s Y V Q Y N s 0.57 Pseudo onas mendocina Mesophilic -

93 NC_007513 |YP_378251.1 s Y 1 Q Y F N s 0.57 Synechococcus sp. Thermophilic -

94 NC_0197571 YP_007145356.1 s Y V Q Y F N s 0.57 Cylindrospermum stagnate Mesophilic +

95 NC_0197711 YP_007156061.1 s Y V Q Y F N s 0.57 Anabaena cylindrica Mesophilic +

96 NC_0059661 YP_046426.1 s Y V Q Y Y N s 0.57 Acinetobacter sp. Mesophilic -

97 NC_018708|YP_006853378.1 s Y V Q Y Y N s 0.57 Acidovorax sp. Mesophilic -

98 NC_0105241 YP_001790118.1 s Y V Q Y Y N s 0.57 Leptothrix cholodnii Mesophilic -

99 NZ_AHJG000000001 WP_010193380.1 s Y 1 Q Y F N s 0.57 Candidatus Nitrosoarchaeum Mesophilic +

100 NC_0134211 YP_003259868.1 s Y V Q Y Y N s 0.57 Pectobacterium wasabiae Mesophilic -

101 NC_0185251 YP_006646896.1 s Y V Q Y Y N s 0.57 Pectobacterium carotovorum Mesophilic -

102 NC_0178451 YP_006283434.1 s Y V Q Y Y N s 0.56 Pectobacterium sp. Mesophilic -

103 NC_007577 |YP_397325.1 s Y 1 Q Y F N s 0.56 Prochlorococcus marinus Mesophilic -

Attorney Docket No. 35327-522001 WO

104 NC_015556|YP_004476124.1 S Y V Q Y Y N S 0.56 Pseudomonas fulva Mesophilic -

105 NC_0097921 YP_001453130.1 S Y V Q Y Y N S 0.56 Citrobacter koseri Mesophilic -

106 NC_013194|YP_003166447.1 S Y V Q Y Y N S 0.56 Candidates Accumulibacter Mesophilic +

107 NC_0129171 YP_003017736.1 S Y V Q Y Y N S 0.56 Pectobacterium carotovorum Mesophilic -

108 NC_0184051 YP_006578678.1 S Y V Q Y Y N S 0.56 Enterobacter cloacae Mesophilic -

109 NC_008786|YP_997959.1 S Y V Q Y Y N S 0.56 Verminephrobacter eiseniae Mesophilic -

110 NC_0129121 YP_003005049.1 S Y V Q Y Y N S 0.56 Dickeya zeae Mesophilic -

111 NC_0230321 P262_02860 S Y V Q Y Y N S 0.56 Cronobacter sakazakii Mesophilic -

112 NC_0230651 YP_008937889.1 S Y V Q Y F N S 0.56 Magnetospirillum gryphiswalden Mesophilic +

113 NC_0087021 YP_931642.1 S Y V Q Y F N S 0.56 Azoarcus sp. Mesophilic -

114 NC_0045471 YP_050239.1 S Y V Q Y Y N S 0.56 Pectobacterium atrosepticum Mesophilic -

115 NC_0168451 YP_005226838.1 S Y V Q Y Y N S 0.55 Klebsiella pneumoniae Mesophilic -

116 NC_0150611 YP_004210833.1 S Y V Q Y Y N S 0.55 Rahnella sp. Mesophilic +

117 NC_001264| NP_285643.1 S Y V Q Y Y N S 0.55 Deinococcus radiodurans Mesophilic +

118 NC_0079731 YP_583107.1 S Y V Q Y Y N S 0.55 Cupriavidus metallidurans Mesophilic -

119 NC_0084631 YP_793325.1 S Y V Q Y Y N S 0.55 Pseudomonas aeruginosa Mesophilic -

120 NC_007969|YP_580259.1 S Y V Q Y Y N S 0.55 Psychrobacter cryohalolentis Psychrophilic -

121 NC_0175321 YP_005940407.1 S Y V Q Y Y N S 0.55 Pseudomonas stutzeri Mesophilic -

122 NC_007298|YP_284662.1 S Y V Q Y Y N S 0.55 Dechloromonas aromatica Mesophilic -

123 NC_009850|YP_001489733.1 s Y V Q Y Y N S 0.55 Arcobacter butzleri Mesophilic -

124 NC_0210461 YP_007845048.1 s Y V Q Y Y N S 0.55 Enterobacter cloacae Mesophilic -

125 NC_023075 |X969_23120 s Y V Q Y Y N S 0.55 Pseudomonas monteilii Mesophilic -

126 NC_013716|YP_003365082.1 s Y V Q Y Y N S 0.55 Citrobacter rodentium Mesophilic -

127 NC_007908| Rfer_3381 s Y V Q Y Y N S 0.55 Albidiferax ferrireducens Mesophilic +

128 NC_0156771 YP_004620409.1 s Y V Q Y Y N S 0.55 Ramlibacter tataouinensis Mesophilic -

129 NC_0138941 YP_003473480.1 s Y V Q Y F N S 0.55 Thermocrinis albus Thermophilic -

130 NC_015726|YP_004684855.1 s Y V Q Y Y N S 0.55 Cupriavidus necator Mesophilic -

131 NC_0148371 YP_004114477.1 s Y V Q Y Y N s 0.55 Pantoea sp. Mesophilic -

132 NC_0145621 YP_003929719.1 s Y V Q Y Y N s 0.55 Pantoea vagans Mesophilic -

133 NC_015138|YP_004235852.1 s Y V Q Y Y N s 0.55 Acidovorax avenae Mesophilic -

134 NC_0087811 YP_981235.1 s Y V Q Y Y N s 0.55 Polaromonas naphthalenivorans Mesophilic -

135 NC_021066|YP_007873403.1 s Y V Q Y Y N s 0.55 Raoultella ornithinolytica Mesophilic +

136 NC_0159681 YP_004828644.1 s Y V Q Y Y N s 0.55 Enterobacter asburiae Mesophilic -

137 NC_0138501 YP_003439644.1 s Y V Q Y Y N s 0.55 Klebsiella variicola Mesophilic -

138 NC_0079481 YP_548240.1 s Y V Q Y Y N s 0.55 Polaromonas sp. Mesophilic -

139 NC_010322 |YP_001671118.1 s Y V Q Y Y N s 0.55 Pseudomonas putida Mesophilic -

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140 NC_0152241 YP_004297604.1 S Y V Q Y Y N S 0.55 Yersinia enterocolitica Mesophi ic -

141 NC_0215911 YP_008137498.1 S Y V Q Y Y N S 0.55 Serratia plymuthica Mesophi ic +

142 NC_009778|YP_001437860.1 S Y V Q Y Y N S 0.55 Cronobacter sakazakii Mesophi ic -

143 NC_016816|YP_005197101.1 S Y V Q Y Y N S 0.55 Pantoea ananatis Mesophi ic -

144 NC_0170751 YP_005438782.1 S Y V Q Y Y N S 0.55 Rubrivivax gelatinosus Mesophi ic +

145 NC_016818|YP_005198188.1 S Y V Q Y Y N S 0.55 Rahnella aquatilis Mesophi ic +

146 NC_018106|YP_006498850.1 S Y V Q Y Y N S 0.55 Klebsiella oxytoca Mesophi ic -

147 NC_0082551 YP_677867.1 S Y V Q Y F N S 0.55 Cytophaga hutchinsonii Mesophi ic -

148 NC_009656|YP_001350899.1 S Y V Q Y Y N S 0.55 Pseudomonas aeruginosa Mesophi ic -

149 NC_0197011 YP_007102831.1 S Y V Q Y F N S 0.55 Pseudanabaena sp. Mesophi ic +

150 NC_009434| PST_3720 S Y V Q Y Y N S 0.55 Pseudomonas stutzeri Mesophi ic -

151 NC_0143061 YP_003740028.1 S Y V Q Y Y N S 0.55 Erwinia billingiae Mesophi ic -

152 NC_0230761 X970_22755 S Y V Q Y Y N S 0.55 Pseudomonas monteilii Mesophi ic -

153 NC_0217411 M495_06585 S Y V Q Y Y N S 0.55 Serratia liquefaciens Mesophi ic +

154 NC_009436|YP_001176715.1 S Y V Q Y Y N S 0.55 Enterobacter sp. Mesophi ic -

155 NC_020829|YP_007659756.1 S Y V Q Y Y N S 0.55 Pseudomonas denitrificans Mesophi ic -

156 NC_0212321 YP_007991487.1 S Y V Q Y Y N S 0.55 Klebsiella pneumoniae Mesophi ic -

157 NC_009256|YP_001118688.1 S Y V Q Y Y N S 0.55 Burkholderia vietnamiensis Mesophi ic -

158 NC_0200631 YP_007340042.1 S Y V Q Y Y N S 0.55 Enterobacteriaceae bacterium Mesophi ic +

159 NC_0212371 YP_007997951.1 S Y V Q Y Y N S 0.55 Pseudomonas protegens Mesophi ic -

160 NC_010528|YP_002005092.1 S Y V Q Y Y N S 0.55 Cupriavidus taiwanensis Mesophi ic -

161 NC_012660|YP_002870258.1 s Y V Q Y Y N S 0.55 Pseudomonas fluorescens Mesophi ic -

162 NC_0216611 PSYCG_05205 s Y V Q Y Y N S 0.55 Psychrobacter sp. Mesophi ic -

163 NC_0105511 YP_001807510.1 s Y V Q Y Y N S 0.55 Burkholderia ambifaria Mesophi ic -

164 NC_0132821 YP_003210547.1 s Y V Q Y Y N S 0.55 Cronobacter turicensis Mesophi ic -

165 NC_0214991 YP_008105445.1 s Y V Q Y Y N S 0.55 Pseudomonas resinovorans Mesophi ic -

166 NC_0106821 YP_001899759.1 s Y V Q Y Y N s 0.55 Ralstonia pickettii Mesophi ic -

167 NC_021878|YP_008330726.1 s Y V Q Y Y N s 0.54 Arcobacter butzleri Mesophi ic -

168 NC_0105011 YP_001751482.1 s Y V Q Y Y N s 0.54 Pseudomonas putida Mesophi ic -

169 NC_0155661 YP_004499842.1 s Y V Q Y Y N s 0.54 Serratia sp. Mesophi ic +

170 NC_010159|YP_001605869.1 s Y V Q Y Y N s 0.54 Yersinia pestis Mesophi ic -

171 NC_0104651 YP_001721602.1 s Y V Q Y Y N s 0.54 Yersinia pseudotuberculosis Mesophi ic -

172 NC_0155671 YP_004504794.1 s Y V Q Y Y N s 0.54 Serratia plymuthica Mesophi ic +

173 NC_0186911 YP_006819365.1 s Y V Q Y Y N s 0.54 Alcanivorax dieselolei Mesophi ic +

174 NC_017559|YP_005996330.1 s Y V Q Y Y N s 0.54 Ralstonia solanacearum Mesophi ic -

175 NC_0098321 YP_001477653.1 s Y V Q Y Y N s 0.54 Serratia proteamaculans Mesophi ic +

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176 NC_015410|YP_004378570.1 S Y V Q Y Y N S 0.54 Pseudomonas mendocina Mesophi ic -

177 NC_0073471 YP_295209.1 S Y V Q Y Y N S 0.54 Ralstonia eutropha Mesophi ic -

178 NC_0166121 YP_005020228.1 S Y V Q Y Y N S 0.54 Klebsiella oxytoca Mesophi ic -

179 NC_0080271 YP_610321.1 S Y V Q Y Y N S 0.54 Pseudomonas entomophila Mesophi ic -

180 NC_0202111 YP_007405216.1 S Y V Q Y Y N S 0.54 Serratia marcescens Mesophi ic +

181 NC_020516|YP_007553848.1 S Y V Q Y Y N S 0.54 Azoarcus sp. Mesophi ic -

182 NC_0087521 YP_971829.1 S Y V Q Y Y N S 0.54 Acidovorax citrulli Mesophi ic -

183 NC_023019| U769_26650 S Y V Q Y Y N S 0.54 Pseudomonas aeruginosa Mesophi ic -

184 NC_0070051 YP_237494.1 S Y V Q Y Y N S 0.54 Pseudomonas syringae Mesophi ic -

185 NC_019936|YP_007238804.1 S Y V Q Y Y N S 0.54 Pseudomonas stutzeri Mesophi ic -

186 NC_011666|YP_002362311.1 S Y V Q Y F N S 0.54 Methylocella silvestris Mesophi ic -

187 NC_015379|YP_004351756.1 S Y V Q Y Y N S 0.54 Pseudomonas brassicacearum Mesophi ic -

188 NC_017920|YP_006331902.1 S Y V Q Y Y N S 0.54 Burkholderia sp. Mesophi ic -

189 NC_017192 |YP_005553223.1 S Y V Q Y Y N S 0.54 Arcobacter sp. Mesophi ic -

190 NC_009648|YP_001335277.1 S Y V Q Y Y N S 0.54 Klebsiella pneumoniae Mesophi ic -

191 NC_0100841 YP_001580663.1 S Y V Q Y Y N S 0.54 Burkholderia multivorans Mesophi ic -

192 NC_0185131 YP_006616708.1 S Y V Q Y Y N S 0.54 Burkholderia cepacia Mesophi ic -

193 NC_0149311 YP_004156925.1 S Y V Q Y Y N S 0.54 Variovorax paradoxus Mesophi ic -

194 NC_007510|YP_368255.1 S Y V Q Y Y N s 0.54 Burkholderia lata Mesophi ic -

195 NC_010170|YP_001628898.1 s Y V Q Y Y N s 0.54 Bordetella petrii Mesophi ic -

196 NC_0106941 YP_001906630.1 s Y V Q Y Y N s 0.54 Erwinia tasmaniensis Mesophi ic -

197 NC_023064| U771_03375 s Y V Q Y Y N s 0.54 Pseudomonas sp. Mesophi ic -

198 NC_010508|YP_001764180.1 s Y V Q Y Y N s 0.54 Burkholderia cenocepacia Mesophi ic -

199 NC_0106221 YP_001858472.1 s Y V a Y Y N s 0.54 Burkholderia phymatum Mesophi ic -

200 NC_0143071 YP_003745265.1 s Y V Q Y Y N s 0.54 Ralstonia solanacearum Mesophi ic -

201 NC_004129|YP_257783.1 s Y V Q Y Y N s 0.54 Pseudomonas protegens Mesophi ic -

202 NC_0200641 YP_007343826.1 s Y V Q Y Y N s 0.54 Serratia marcescens Mesophi ic +

203 NC_0202091 YP_007400304.1 s Y V Q Y Y N s 0.54 Pseudomonas poae Mesophi ic -

204 NC_0074921 YP_346323.1 s Y V Q Y Y N s 0.54 Pseudomonas fluorescens Mesophi ic -

205 NC_0215771 M062_25640 s Y V Q Y Y N s 0.54 Pseudomonas aeruginosa Mesophi ic -

206 NC_008390|YP_772680.1 s Y V Q Y Y N s 0.54 Burkholderia ambifaria Mesophi ic -

207 NC_0045781 NP_794619.1 s Y V Q Y Y N s 0.54 Pseudomonas syringae Mesophi ic -

208 NC_012856|YP_002981823.1 s Y V Q Y Y N s 0.54 Ralstonia pickettii Mesophi ic -

209 NC_018028|YP_006456254.1 s Y V Q Y Y N s 0.54 Pseudomonas stutzeri Mesophi ic -

210 NC_014640|YP_003981249.1 s Y V Q Y Y N s 0.54 Achromobacter xylosoxidans Mesophi ic -

211 NC_0168251 YP_005202834.1 s Y V Q Y Y N s 0.54 Salmonella enterica Mesophi ic -

Attorney Docket No. 35327-522001 WO

212 NC_0116621 YP_002890891.1 S Y V Q Y Y N S 0.54 Thauera sp. Mesophilic -

213 NC_0129971 YP_003075463.1 S Y V Q Y Y N S 0.54 Teredinibacter turnerae Mesophilic -

214 NC_0126911 YP_002892824.1 S Y V Q Y Y N S 0.54 Tolumonas auensis Mesophilic -

215 NC_0155831 YP_004538852.1 S Y V Q Y Y N S 0.54 Novosphingobium sp. Mesophilic -

216 NC_0088251 YP_001019894.1 S Y V Q Y Y N S 0.54 Methylibium petroleiphilum Mesophilic -

217 NC_0212871 YP_008038261.1 S Y V Q Y Y N S 0.53 Burkholderia sp. Mesophilic -

218 NC_0185271 YP_006653903.1 S Y V Q Y Y N S 0.53 Burkholderia pseudomallei Mesophilic -

219 NC_0175741 YP_006029230.1 S Y V Q Y Y N S 0.53 Ralstonia solanacearum Mesophilic -

220 NC_011894|YP_002499775.1 S Y V Q Y Y N S 0.53 Methylobacterium nodularis Mesophilic -

221 NC_015856|YP_004753495.1 S Y V Q Y Y N S 0.53 Collimonas fungivorans Mesophilic -

222 NC_0097201 YP_001419028.1 S Y V Q Y Y N S 0.53 Xanthobacter autotrophicus Mesophilic -

223 NC_023045 | I533_13880 S Y V Q Y Y N S 0.53 Alteromonas macleodii Mesophilic -

224 NC_0180121 YP_006414170.1 S Y V Q Y Y N S 0.53 Thiocystis violascens Mesophilic +

225 NC_022904| U875_22200 S Y V Q Y Y N S 0.53 Pandoraea pnomenusa Mesophilic +

226 NC_0082601 YP_694229.1 S Y V Q Y Y N S 0.53 Alcanivorax borkumensis Mesophilic +

227 NC_0087021 YP_932178.1 S Y V Q Y Y N S 0.53 Azoarcus sp. Mesophilic -

228 NC_017080|YP_005445276.1 S Y V Q Y F N S 0.53 Phycisphaera mikurensis Mesophilic +

229 NC_009080|YP_001081579.1 S Y V Q Y Y N S 0.53 Burkholderia mallei Mesophilic -

230 NC_014166|YP_003655224.1 S Y V Q Y Y N S 0.53 Arcobacter nitroflgilis Mesophilic -

231 NC_0165891 YP_004977834.1 S Y V Q Y Y N S 0.53 Burkholderia sp. Mesophilic -

232 NC_0212851 YP_008030417.1 S Y V Q Y Y N S 0.53 Achromobacter xylosoxidans Mesophilic -

233 NC_0074341 YP_334499.1 s Y V Q Y Y N S 0.53 Burkholderia pseudomallei Mesophilic -

234 NC_023018|X636_11960 s Y V Q Y Y N S 0.53 Pandoraea sp. Mesophilic +

235 NC_0096541 YP_001339814.1 s Y V Q Y Y N S 0.53 Marinomonas sp. Mesophilic -

236 NC_0127241 YP_002910660.1 s Y V Q Y Y N S 0.53 Burkholderia glumae Mesophilic -

237 NC_017059|YP_005417729.1 s Y V Q Y F N S 0.53 Rhodospirillum photometricum Mesophilic +

238 NC_0087091 YP_944287.1 s Y V Q Y Y N s 0.53 Psychromonas ingrahamii Psychrophilic -

239 NC_011369|YP_002282556.1 s Y V Q Y Y N s 0.53 Rhizobium leguminosarum Mesophilic -

240 NC_0153811 YP_004359471.1 s Y V Q Y Y N s 0.53 Burkholderia gladioli Mesophilic -

241 NC_0211731 YP_007917465.1 s Y V Q Y Y N s 0.53 Burkholderia thailandensis Mesophilic -

242 NC_0105051 YP_001754121.1 s Y V Q Y Y N s 0.52 Methylobacterium radiotolerans Mesophilic -

243 NC_0140341 YP_003577390.1 s Y V Q Y Y N s 0.52 Rhodobacter capsulatus Mesophilic -

244 NC_0076451 YP_435644.1 s Y V Q Y Y N s 0.52 Hahella chejuensis Mesophilic -

245 NC_0111381 MADE_1014320 s Y V Q Y Y N s 0.52 Alteromonas macleodii Mesophilic -

246 NC_0155541 YP_004469428.1 s Y V Q Y Y N s 0.52 Alteromonas sp. Mesophilic -

247 NC_0166421 YP_005081493.1 s Y V Q Y Y N s 0.52 Pseudovibrio sp. Mesophilic +

Attorney Docket No. 35327-522001 WO

248 NC_009659|YP_001353496.1 S Y V Q Y Y N S 0.52 Janthinobacterium sp. Mesophi ic -

249 NC_008340|YP_741033.1 S Y V Q Y F N S 0.52 Alkalilimnicola ehrlichii Mesophi ic -

250 NC_008836|YP_001028523.1 S Y V Q Y Y N S 0.52 Burkholderia mallei Mesophi ic -

251 NC_0079121 YP_525702.1 S Y V Q Y Y N S 0.52 Saccharophagus degradans Mesophi ic -

252 NC_0109951 YP_001981733.1 S Y V Q Y Y N S 0.52 Cellvibrio japonicus Mesophi ic -

253 NC_020514|YP_007546992.1 S Y V Q Y Y N S 0.52 Glaciecola psychrophila Mesophi ic +

254 NC_023137 |Gal_03429 S Y V Q Y Y N S 0.52 Phaeobacter gallaeciensis Mesophi ic +

255 NC_0200621 YP_007337601.1 S Y V Q Y Y N S 0.52 Rhizobium tropic! Mesophi ic -

256 NC_0170821 YP_005448343.1 S Y V Q Y Y N S 0.52 Bradyrhizobium sp. Mesophi ic -

257 NC_007925 |YP_533556.1 S Y V Q Y Y N S 0.52 Rhodopseudomonas palustris Mesophi ic -

258 NC_0105111 YP_001769493.1 S Y V Q Y Y N S 0.52 Methylobacterium sp. Mesophi ic -

259 NC_0143231 YP_003778087.1 S Y V Q Y Y N S 0.52 Herbaspirillum seropedicae Mesophi ic -

260 NC_0165851 YP_004973582.1 S Y V Q Y Y N S 0.52 Azospirillum lipoferum Mesophi ic +

261 NC_0145321 YP_003897340.1 S Y V Q Y Y N S 0.52 Halomonas elongata Mesophi ic -

262 NC_012982 | Hbal_2718 S Y V Q Y F N S 0.52 Hirschia baltica Mesophi ic -

263 NC_0138551 YP_003450097.1 S Y V Q Y Y N S 0.52 Azospirillum sp. Mesophi ic +

264 NC_008380|YP_769320.1 S Y V Q Y Y N S 0.52 Rhizobium leguminosarum Mesophi ic -

265 NC_0098311 YP_001475613.1 S Y L Q Y F N S 0.52 Shewanella sediminis Psychrophilic -

266 NC_0155591 YP_004483096.1 S Y V Q Y Y N S 0.52 Marinomonas posidonica Mesophi ic -

267 NC_0179641 YP_006379678.1 S Y V Q Y Y N S 0.52 Advenella kashmirensis Mesophi ic +

268 NC_0141171 YP_003604284.1 S Y V Q Y Y N S 0.52 Burkholderia sp. Mesophi ic -

269 NC_0030781 NP_438057.1 S Y V Q Y Y N S 0.52 Sinorhizobium meliloti Mesophi ic -

270 NC_015596|YP_004556797.1 S Y V Q Y Y N S 0.52 Sinorhizobium meliloti Mesophi ic -

271 NC_007951 |YP_557358.1 s Y V Q Y Y N S 0.52 Burkholderia xenovorans Mesophi ic -

272 NC_0156751 YP_004612695.1 s Y V Q Y Y N S 0.52 Mesorhizobium opportunistum Mesophi ic -

273 NC_012586|YP_002824376.1 s Y V Q Y Y N S 0.52 Sinorhizobium fredii Mesophi ic -

274 NC_009620|YP_001312922.1 s Y V Q Y Y N S 0.52 Sinorhizobium medicae Mesophi ic -

275 NC_0230651 YP_008937892.1 s Y V Q Y Y N s 0.52 Magnetospirillum gryphiswalden Mesophi ic +

276 NC_017059|YP_005417155.1 s Y V Q Y Y N s 0.52 Rhodospirillum photometricum Mesophi ic +

277 NC_015276|YP_004311256.1 s Y V Q Y Y N s 0.52 Marinomonas mediterranea Mesophi ic -

278 NC_0225351 YP_008633407.1 s Y V Q Y Y N s 0.52 Rhizobium sp. Mesophi ic -

279 NC_020888|YP_007684197.1 s Y V Q Y Y N s 0.52 Thalassolituus oleivorans Mesophi ic +

280 NC_0044631 NP_768088.1 s Y V Q Y Y N s 0.52 Bradyrhizobium diazoefficiens Mesophi ic -

281 NC_0086871 YP_917779.1 s Y V Q Y Y N s 0.52 Paracoccus denitrificans Mesophi ic -

282 NC_0166131 YP_005022836.1 s Y V Q Y Y N s 0.52 Vibrio sp. Mesophi ic +

283 NC_0030621 NP_355366.2 s Y V Q Y Y N s 0.52 Agrobacterium fabrum Mesophi ic -

Attorney Docket No. 35327-522001 WO

284 NC_015259|YP_004302144.1 S Y V Q Y Y N S 0.52 Polymorphum gilvum Mesophi ic -

285 NC_0180001 YP_006396988.1 S Y V Q Y Y N S 0.52 Sinorhizobium fredii Mesophi ic -

286 NC_0166171 YP_005032267.1 S Y V Q Y Y N S 0.52 Azospirillum brasilense Mesophi ic +

287 NC_0106811 YP_001894597.1 S Y V Q Y Y N S 0.52 Burkholderia phytqfirmans Mesophi ic -

288 NC_0119851 YP_002545350.1 S Y V Q Y Y N S 0.52 Agrobacterium radiobacter Mesophi ic -

289 NC_0149231 YP_004143235.1 S Y V Q Y Y N S 0.52 Mesorhizobium ciceri Mesophi ic -

290 NC_018268|YP_006559381.1 S Y V Q Y Y N S 0.52 Marinobacter sp. Mesophi ic +

291 NC_0155721 YP_004513420.1 S Y V Q Y Y N S 0.52 Methylomonas methanica Mesophi ic -

292 NC_015136|YP_004227222.1 S Y V Q Y Y N S 0.51 Burkholderia sp. Mesophi ic -

293 NC_017249|YP_005613229.1 S Y V Q Y Y N S 0.51 Bradyrhizobium japonicum Mesophi ic -

294 NC_0186951 YP_006833023.1 S Y V Q Y Y N S 0.51 Burkholderia phenoliruptrix Mesophi ic -

295 NC_0168151 YP_005191649.1 S Y V Q Y Y N S 0.51 Sinorhizobium fredii Mesophi ic -

296 NC_0077611 YP_470808.1 S Y V Q Y Y N S 0.51 Rhizobium etli Mesophi ic -

297 NC_0151831 YP_004279628.1 S Y V Q Y Y N S 0.51 Agrobacterium sp. Mesophi ic -

298 NC_012850|YP_002977104.1 S Y V Q Y Y N S 0.51 Rhizobium leguminosarum Mesophi ic -

299 NC_0099371 YP_001524674.1 S Y V Q Y Y N S 0.51 Azorhizobium caulinodans Mesophi ic -

300 NC_002678| NP_102500.1 S Y V Q Y Y N S 0.51 Mesorhizobium loti Mesophi ic -

301 NC_0087401 YP_960262.1 S Y V Q Y Y N S 0.51 Marinobacter aquaeolei Mesophi ic +

302 NC_0170671 YP_005430828.1 S Y V Q Y Y N S 0.51 Marinobacter hydrocarbonoclast Mesophi ic +

303 NC_0199731 YP_007305659.1 S Y V Q Y Y N S 0.51 Mesorhizobium australicum Mesophi ic -

304 NC_017326|YP_005722442.1 S Y V Q Y Y N S 0.51 Sinorhizobium meliloti Mesophi ic -

305 NC_0182861 YP_006564404.1 s Y V Q Y Y N S 0.51 Phaeobacter gallaeciensis Mesophi ic +

306 NC_0204531 YP_007516150.1 s Y V Q Y Y N S 0.51 Bradyrhizobium oligotrophicum Mesophi ic -

307 NC_009379|YP_001155981.1 s Y V Q Y Y N S 0.51 Polynucleobacter necessarius Mesophi ic -

308 NC_0148341 YP_004108031.1 s Y V Q Y Y N S 0.51 Rhodopseudomonas palustris Mesophi ic -

309 NC_0134221 YP_003262986.1 s Y V Q Y Y N S 0.51 Halothiobacillus neapolitanus Mesophi ic -

310 NC_0094851 YP_001242809.1 s Y V Q Y Y N s 0.51 Bradyrhizobium sp. Mesophi ic -

311 NC_009428|YP_001167199.1 s Y V Q Y Y N s 0.51 Rhodobacter sphaeroides Mesophi ic -

312 NC_011989|YP_002550517.1 s Y V Q Y Y N s 0.51 Agrobacterium vitis Mesophi ic -

313 NC_0085761 YP_864943.1 s Y V Q Y Y N s 0.51 Magnetococcus marinus Mesophi ic +

314 NC_0219911 YP_008391987.1 s Y V Q Y Y N s 0.51 Acetobacter pasteurianus Mesophi ic -

315 NC_017956|YP_006371145.1 s Y V Q Y Y N s 0.51 Tistrella mobilis Mesophi ic +

316 NC_0186971 YP_006836550.1 s Y V Q Y Y N s 0.51 Cycloclasticus sp. Mesophi ic +

317 NC_0115651 YP_002308907.1 s Y V Q Y F N s 0.51 Candidatus Azobacteroides Mesophi ic +

318 NC_003911 |SPO1710 s Y V Q Y Y N s 0.51 Ruegeria pomeroyi Mesophi ic -

319 NC_0079631 YP_574362.1 s Y V Q Y Y N s 0.51 Chromohalobacter salexigens Mesophi ic -

Attorney Docket No. 35327-522001 WO

320 NC_0219171 YP_008372709.1 S Y V Q Y Y N S 0.51 Cycloclasticus zancles Mesophilic +

321 NC_0219051 REMIM1_CH03377 S Y V Q Y Y N S 0.51 Rhizobium etli Mesophilic -

322 NC_0084351 YP_782650.1 S Y V Q Y Y N S 0.51 Rhodopseudomonos palustris Mesophilic -

323 NC_0134461 CtCNBl_4515 S Y V Q Y Y N S 0.51 Comamonas testosteroni Mesophilic -

324 NC_022543 | YP_008641473.1 S Y V Q Y Y N S 0.5 Vibrio nigripulchritudo Mesophilic +

325 NC_007493 | RSP_0301 S Y V Q Y Y N S 0.5 Rhodobacter sphaeroides Mesophilic -

326 NC_0142171 YP_003693312.1 S Y V Q Y Y N S 0.5 Starkeya novella Mesophilic -

327 NC_0171111 YP_005484746.1 S Y V Q Y Y N S 0.5 Acetobacter pasteurianus Mesophilic -

328 NC_007958|YP_570634.1 S Y V Q Y Y N S 0.5 Rhodopseudomonos palustris Mesophilic -

329 NC_010506|YP_001762134.1 S Y L Q Y F N S 0.5 Shewanella woodyi Mesophilic -

330 NC_010571 |YP_001821102.1 S Y V Q Y Y N S 0.5 Opitutus terrae Mesophilic -

331 NC_008209| RD1_2166 S Y V Q Y Y N S 0.5 Roseobacter denitriflcans Mesophilic -

332 NC_015730|YP_004690268.1 S Y V Q Y Y N S 0.5 Roseobacter litoralis Mesophilic -

333 NC_015174|YP_004270640.1 S Y L Q Y F N S 0.49 Planctomyces brasiliensis Mesophilic -

334 NC_0099521 YP_001534029.1 S Y V Q Y Y N S 0.49 Dinoroseobacter shibae Mesophilic -

335 NC_017506|YP_005886573.1 S Y V Q Y Y N S 0.49 Marinobacter adhaerens ? +

336 NC_0143941 YP_003847887.1 S Y V Q Y F N S 0.49 Gallionella capsiferriformans Mesophilic -

337 NZ_AJVJ000000001 WP_014963736.1 S Y V Q Y F N S 0.49 Methanobacterium sp. ? N/a

338 NC_0173841 YP_005795720.1 S Y V Q Y Y N S 0.49 Ketogulonicigenium vulgare Mesophilic -

339 NC_0186551 YP_006774297.1 S Y V Q Y F N S 0.49 Candidatus Nitrosopumilus Mesophilic +

340 NC_0212911 YP_008046494.1 s Y V Q Y Y N S 0.49 Spiribacter salinus Mesophilic +

341 NC_0223571 YP_008545103.1 s Y V Q Y F N S 0.48 Sulfuricella denitriflcans Mesophilic +

342 NZ_AJVI000000001 WP_014963736.1 s Y V Q Y F N S 0.48 Methanobacterium sp. ? N/a

343 NC_016078|YP_004901286.1 s Y V Q Y Y N S 0.48 Pelagibacterium halotolerans Mesophilic +

344 NC_0209111 YP_007703090.1 s Y V Q Y Y N S 0.48 Octadecabacter antarcticus Mesophilic +

345 NC_0209081 YP_007700904.1 s Y V Q Y Y N S 0.48 Octadecabacter arcticus Mesophilic +

346 NC_014008|YP_003549337.1 s Y V Q Y Y N S 0.48 Coraliomargarita akajimensis Mesophilic -

347 NC_0161121 YP_004916295.1 s Y V Q Y F N s 0.46 Methylomicrobium alcaliphilum Mesophilic +

348 NC_0134401 YP_003269659.1 s Y L Q Y Y N s 0.46 Haliangium ochraceum Mesophilic -

349 NC_0094811 YP_001224322.1 s Y V Q Y Y N s 0.43 Synechococcus sp. Thermophilic -

Attorney Docket No. 35327-522001 WO

The distribution of Hamming distance values (FIG. 5C) shows that sequences are either members of the UBP functional family (H=0), or not (H>1), but very few are intermediate (H=l). This behavior reflects a selective pressure that ensures ligand-binding specificity. From a practical point of view, it confirms the reliability of the SAFE method.

EXAMPLE 5. SENSOR ENGINEERING PHASE 4: CYSTEINE MUTANT SCANS AND FLUOROPHORE SCREENING TO IDENTIFY FLUORESCENTLY RESPONSIVE UREA SENSORS

Semi-synthetic FRSs can be engineered by site-specifically attaching thiol-reactive, environmentally sensitive fluorophores that respond to ligand-mediated conformational changes. Identification of FRS candidates that can be used for sensing applications comprises four steps:

1. Cysteine scan. Mutant urea-binding proteins containing single cysteines are

constructed for site-specific attachment of thiol-reactive fluorophores. General structural principles have been established to identify positions in PBPs where attached single fluorophores are likely to exhibit ligand-dependent responses (de Lorimier et al., 2002, Protein Sci, 11, 2655-75). Candidate positions fall into three classes: endosteric, replacing a residue that contacts the ligand directly; peristeric, located at the rim of the binding site; allosteric (Marvin et al., 1997, Proc Natl Acad Sci USA, 94, 4366-71; Marvin, 1998, J Am Chem Soc, 120, 7-11), located outside the binding site at sites that undergo local structural changes in concert with the hinge- bending motion.

2. Fluorophore screening. Thiol-reactive, environmentally sensitive fluorophores are attached to each cysteine mutant prepared in step 1.

3. Evaluation of the urea-mediated change of all the fluorescent conjugates prepared in step 2. Responses to ligand binding in which there is both a change in fluorescence emission intensity and spectral shape are essential for chemometric applications, because such changes enable ratiometric measurements. Changes in spectral shape typically are accompanied by a shift in the wavelength of the emission intensity maxima. Three classes of fluorescent responses are possible:

i. No response. Attorney Docket No. 35327-522001 WO ii. Monochromatic response (emission intensity increases or decreases without a change in spectral shape)

iii. Dichromatic response (both intensity and spectral shape changes) which can be classified into two sub-classes:

i. Hypsochromatic: emission intensity shifts to shorter wavelengths upon binding ligand ("blue shift").

ii. Bathochromatic: emission intensity shifts to longer wavelengths upon binding ligand ("red shift").

4. Double labeling strategies to convert monochromatic responses into dichromatic signals, or to improve upon weak dichromatic responses.

We constructed 20 single cysteine mutants in csUBP7, exploring 7 endosteric, 12 peristeric, and 1 allosteric position (FIG. 9). At each position we attached the Prodan-derived fiuorophores Acrylodan and Badan, which differ by one methylene group in their thiol- reactive linker. The fluorescent responses of these conjugates was determined initially as a function of urea concentration and temperature (FIG. 10). This thermal landscape analysis showed that 13 of these positions, representing all three classes of attachment sites, exhibited a fluorescent response to urea binding for at least one conjugate (Table 7). The ligand dependence of the emission spectra shapes was determined for these conjugates (Table 8). At least one conjugate at 11 of the 13 positions exhibited a dichromatic response, suitable for ratiometric measurements (see FIG. 11 for an example). In the dichromatic responses of the Acrylodan or Badan conjugates, ligand-mediated changes in emission intensity spectral shapes arise from redistribution of the populations of 'blue' and 'green' emission states (Table 8), corresponding to distinct excited state transition dipoles. Such a redistribution does not occur in monochromatic responses.

Attorney Docket No. 35327-522001 WO Table 7. Response of bsUBP3, ctUBP6, and csUBP7 Acrylodan and Badan conjugates*.

"Measured in a Roche LightCycler (see Materials and methods).

bA, Acrylodan; B, Badan.

cy, yes; n, no. Attorney Docket No. 35327-522001 WO

Table 8. Responses of Acrylodan and Badan csUBP7 conjugates".

"Determined by fitting the ratiometric signal of the intensities measured at λΐ and λ2 to equation 1-6.

bThe PCS comprises S92, Yl l l, VI 13, Q114, Y157, F159, N211, S238.

ca, allosteric; e, endosteric; p, peristeric.

dm, monochromatic; d, dichromatic (i.e. spectral shape changes); 0, no change.

e+, increases in response to urea; -, decreases; 0, no change.

fEstimated change in populations of major emission bands: blue, (maxima < 500 nm); g, green (maxima > 500 nm); b/g, mixed population.

We also constructed a cysteine scan at several equivalent positions in the bsUPB3 and ctUBP6 homologs (FIG. 9) and evaluated the urea responses of Acrylodan or Badan conjugates using thermal melts (Table 7). Ligand-dependent shifts in emission intensity wavelengths were determined for a subset of these mutants (Table 9). In all three homologs that were tested, equivalent residue positions in the sequence alignment exhibited similar responses, consistent with structural conservation and generality of the coupling mechanisms within this family of proteins.

Attorney Docket No. 35327-522001 WO

Table 9. Urea response of Acrylodan and Badan conjugates in a cysteine scan of the ctUBP6 scaffold.

"a, allosteric; e, endosteric; p, peristeric.

bm, monochromatic; d, dichromatic (i.e. spectral shape change).

°A, Acrylodan; B, Badan.

dnoisy data and or bad fit.

enb; no binding, nd; not determined.

In the csUBP7 homolog, we further tested the urea responses of several other fluorescent conjugates that represent some of the major fluorophore classes (FIG. 12). These conjugates (Table 10) were all attached to a 186C variant that also contained the Ql 14A mutation which tunes the urea affinity to optimize responses in the clinical concentration range (see next section for construction of this mutant). Several conjugates exhibited large monochromatic intensity changes, most notably Alexa532 (~5-fold increase) and Oregon Green (~2-fold increase). IAEDANS exhibited a dichromatic response.

Attorney Docket No. 35327-522001 WO

"λεχ, preferred excitation wavelength (from supplier); observed maximum emission wavelength of the apo-protein; ^apo imax, observed intensity at ^"λ^; ^sa %nax, observed maximum emission wavelength of the urea complex; ^sal / _max , observed intensity at ^sa ^max; *™ ^β Κ _ά , affinity determined from fit of equation 1 to the monochromatic emission intensities. Emission spectra were measured on the Nanodrop3300, using -10 μΜ protein. The observed absolute emission intensities are a rough guide to the relative brightness of the conjugate, because the protein concentration was approximately the same for each experiment. See Table 6 for description of fits. Used linear baselines for saturated protein.

bAbbreviations, chemical names and supplier catalogue numbers as follows: Acrylodan (A433); Badan (B6057); 5-IAF (130451); Oregon Green 488 (O6034); CPM (D346); IANBD (D2004); IAEDANS (114); Pacific Blue (P30506); BODIPY 499 (D20350); BODIPY 507 (D6004); BODIPY 577 (D20351); Alexa 532 (A10255); Alexa 555 (A20346); Texas Red (T6008); PyMPO (M6026) from Life Technologies and Cy5 (13080) from Lumiprobe.

cThe Nanodrop3300 fixed wavelength LED that most closely matched λ _βχ was used.

Finally, we tested whether ngmFRET effects in doubly labeled proteins could improve ratiometric signaling. To this end, we fused a small, disulfide-containing domain, PZif (Smith et al., 2005, Protein Sci, 14, 64-73) to the C-terminus of several csUBP7 cysteine mutants (Table 11). This arrangement enables independent, site-specific labeling with two different, thiol-reactive fluorophores by first reacting at the unprotected thiol in the csUBP7, followed by a reduction of the βΖίί disulfide to deprotect and label this second site Attorney Docket No. 35327-522001 WO with a second fluorophore. The first fluorophore, attached to csUBP responds directly to urea binding (directly responsive partner), whereas the second one, attached to the βΖίί fusion, does not (indirectly responsive partner). Indirectly responsive partners are selected according to their excitation and emission characteristics such that ngmFRET is established with the directly responsive partner. Under favorable circumstances, monochromatic responses of the directly responsive partner or weak dichromatic responses can be converted in to strong ratiometric signals, by exploiting ligand-induced modulation of non-geometrical factors affecting ngmFRET such as changes in spectral overlap between the two partnered fluorophores, and alteration of non-radiative decay rates in the directly responsive partner. The mechanism for ngmFRET effects is detailed in Materials and Methods and PCT

International Patent Application No. PCT/US 16/62958, filed November 19, 2016, the entire content of which is incorporated herein by reference.

Table 11. Urea affinities of csUBP7 pZif conjugates based on ngmFRET

acsUBP7 and βΖίί indicate attachment site for the fluorophores. OG, Oregon Green; PB, Pacific Blue.

bIntensity changes of donor and acceptor with increasing urea concentration: 0, no change; +, increase; -, decrease.

Qualitative assessment of energy transfer coupling factor, φ, based on relative intensities of the donor (J _D ) and acceptor (JA) emission intensities: w, weak ¾ » /A); m, medium ¾ * JA); strong (J _D « JA). Medium coupling gives the best dichromatic responses.

dSee Materials and methods for fitting procedures.

''Weak or no response due to extensive overlap of donor and acceptor emissions.

fNoisy data.

gSmall change (if any). Attorney Docket No. 35327-522001 WO

Several dichromatic and monochromatic csUBP7 Acrylodan and Badan conjugates were combined as ngmFRET directly responsive donors with pZif Alexa532 indirectly responsive acceptors (Table 11). In several cases, the resulting ratiometric responses improved significantly. For instance, neither directly responsive fluorophore exhibits strong dichromatic responses when coupled by themselves at positions 26C, but in conjunction with the indirectly responsive Alexa532 conjugate, good ratiometric responses are observed. Both donor and acceptor fluorophores undergo opposing changes in emission intensities, consistent with a mechanism that is dominated by a change in spectral overlap between the two partners. This behavior is consistent with the ligand-mediated redistribution between the two green and blue excited state transition dipoles of the two singly labeled conjugates at this position (Table 8): Acrylodan undergoes a bathochromic shift, whereas Badan exhibits slight hypsochromicity. Accordingly, the spectral overlap between the directly responsive and indirectly responsive ngmFRET partners in the Acrylodan conjugate increases, resulting in enhancement of the energy transfer coupling factor, φ, and a corresponding loss in donor and gain in acceptor emission intensities (Table 12, cP<fi ^~ ). In the Badan conjugate, the opposite response pattern is observed, because the hypsochromic shift diminishes spectral overlap (Table 12,

Attorney Docket No. 35327-522001 WO Table 12. Qualitative analysis of the patterns of donor and acceptor emission intensity changes in ngmFRET ¹

aThe effects of increasing or decreasing quenching in the directly responsive ngmFRET partner (d for donors, a for acceptors) or the energy transfer coupling (φ) between the donor and acceptor are tabulated. The consequences of using a directly responsive donor or acceptor are examined. Changes in quenching and energy transfer coupling parameters can occur singly or in combination, leading to 16 possible models. The models examine the effects of the direction of change in quenching parameters (no change, d° or a ⁰ ; increase c or a ; decrease, d or d) and the energy transfer coupling factor (no change, <ft; increase, ; decrease, ψ) on the patterns in the direction of change of the donor, QD (equation 16) or acceptor, QA (equation 18) quantum yields, and their ratio, QAIQD (equation 19):†, increase; • , decrease; 0, no change; *, response is dependent on precise quantitation rather than direction of change in the underlying parameter values.

The monochromatic response of the directly responsive acceptor Alexa532 conjugate at 186C in csUBP7 (Table 10) was converted into a dichromatic signal by partnering with a indirectly responsive donor Acrylodan placed in the βΖίί fusion domain (FIG. 13). Both indirectly responsive donor and directly responsive acceptor intensities changed in response to urea, in opposite directions. This pattern can occur only if the energy transfer coupling factor, φ, changes between the partners as a consequence of a change in spectral overlap. Furthermore, the loss in donor and gain in acceptor intensities indicate a bathochromic shift of the directly responsive acceptor absorbance spectrum in response to ligand binding (Table 12, a°<f). Given that the response of the singly labeled directly responsive Alexa532 Attorney Docket No. 35327-522001 WO conjugate is monochromatic (Table 10), this conclusion indicates that Alexa532 undergoes a urea-mediated switch between two electronic transitions, only one of which is fluorescent, but both of which can be excited by resonance energy transfer.

The average energy transfer coupling strength plays in important role in determining the effectiveness for ratiometric of a particular ngmFRET fluorophore pair (Table 12).

Coupling strengths can be scored qualitatively based on the relative sizes of the donor (¾) and acceptor (JA) emission intensities (also taking into account the differences in the quantum yield of the two partners). If the donor intensity exceeds that of the acceptor on average, than coupling is weak (e.g. csUBP7 27C-Acrylodan-pZif-Alexa523, Table 11). Conversely if J consistently exceeds JD, coupling is strong, because most of the donor excited state resonance is transferred to the acceptor (e.g. csUBP7 186C-Alexa532-pZif-Badan). Medium-strength coupling occurs when both intensities are on par. Extremes in coupling strength do not lead to usable ratiometric responses, because the intensities of one of the two partners remain low, thereby increasing the overall error in the signal. For the same directly responsive partner, coupling strengths are highly dependent on the indirectly responsive partner. For instance, the directly responsive 186C Alexa532 acceptor partnered with a indirectly responsive Acrylodan donor exhibits medium coupling strength, whereas partnered with a indirectly responsive Badan donor such strong coupling is established that the Badan emission intensity is barely observable. It is remarkable that a small change in the geometry of the linker group that mediates attachment of the same naphthalene fluorescent core (FIGS. 12A, B) results in such large differences. The Badan linker is one methylene group shorter than that of the Acrylodan, possibly causing differences in the conformational degrees of freedom of these two conjugates, which in turn could lead to differences in the average orientations between the ngmFRET partners and hence in resonance transfer efficiencies (t effects, see Materials and Methods).

EXAMPLE 6. SENSOR ENGINEERING PHASE 5: AFFINITY TUNING

Normal blood urea concentrations range from about 1.8 mM to about 7.1 mM (Burtis, 2012, Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Elsevier).

Measurements using reagentless sensors are most sensitive at analyte concentrations that match the dissociation constant (de Lorimier et al., 2002, Protein Sci, 11, 2655-75; Marvin et al., 1997, Proc Natl Acad Sci USA, 94, 4366-71). The urea affinity of csUBP7 186C ^• Acrylodan is too high and must therefore be "tuned" by raising the K _& value. Attorney Docket No. 35327-522001 WO The mutations that alter urea affinities fall into four classes:

1. Alteration of direct interactions in the PCS between the protein and the bound urea.

2. Manipulation of the equilibrium between the open (ligand-free) and closed (ligand- bound) states (Marvin and Hellinga, 2001, Nat Struct Biol, 8, 795-8).

3. Indirect interactions that alter the geometry of the binding site.

4. Alteration of interactions between the protein and the fluorescent conjugate.

The effects of mutations representing the first three classes of mutations were determined in the csUBP7 186C-Acrylodan conjugate. First, an alanine scan of the eight residues in the PCS was conducted to evaluate the relative contributions of these direct interactions (Table 13). This analysis revealed that the hydrogen bond formed by S92 to the amino common to both urea and acetamide (amine A) is critical. The loss of the second, more distant interaction by Yl 11 does affect binding strongly. The contributions of the three residues that interact with the amine not present in acetamide (amine B) differ by an order of magnitude. Most important is Ν211, the loss of which causes a large loss in affinity, whereas loss of either of the other two residues has much smaller effect. Both the carbonyl hydrogen bond by Y157 and the extensive van der Waals contact by F159 are important, as expected. Loss of the van der Waals interaction in VI 13A diminishes affinity as much as F159A, indicating that VI 13 functions as the second van der Waals surface that "sandwiches" the bound urea, analogous to the geometries observed in many other PBPs that bind a wide variety of organic ligands.

Table 13. Alanine scan of the PCS residues of csUBP7 186C labeled with Acrylodan".

a Determined by fitting the ratiometric signal of the intensities measured at λΐ and λ2 to equation 1-6.

bnb, no binding.

cMeasured in a Roche LightCycler (see Materials and methods). Attorney Docket No. 35327-522001 WO

Exploration of class 1 effects was limited to the three-residue cluster forming interactions with amine group B and to the van der Waals interactions of VI 13. (Table 14). Even though the N211 A mutant nearly abolishes binding, more subtle effects can be achieved by charge (N21 ID), geometry (N211Q, N21 IS, N21 IT), or a combination of both (N21 IE). Interestingly, the introduction of charge in N21 IE weakens affinity, whereas Ql 14E improves binding by an order of magnitude. The consequences of manipulating the van der Waals interactions of VI 13 are complex. Loss of this interaction in VI 13A weakens binding significantly. The introduction of a polar group in VI 13T has only a small effect. Bulkier polar groups weaken binding, but VI 13Q has a 10-fold stronger affinity than either VI 13N or VI 13H, suggesting that the glutamine forms an unanticipated hydrogen bond.

Table 14. Affinity-tuning mutations of csUBP7 186C-Acrylodan conjugates.

Attorney Docket No. 35327-522001 WO

a Determined by fitting the ratiometric signal of the intensities measured at λΐ and λ2 to equation 1-6.

bn/b, no binding.

cMeasured in a Roche LightCycler (see Materials and methods).

Class 2 effects were explored by removing hydrogen bonds between the N- and C- terminal domains (Table 14), identified in the csUBP7 structure. The most effective of these was a double mutant (S30I, E241 A) that removes two such inter-domain interactions, confirming that manipulation of conformational equilibria is an effective strategy for manipulating ligand affinities(Marvin and Hellinga, 2001, Nat Struct Biol, 8, 795-8).

Class 3 interactions were tested by removing secondary shell interactions. The glutamate at position 116 stabilizes the conformation of S92, the residue that binds the second urea amino group. Each of these has a large effect on urea affinity (Table 14), consistent with the observation that S92A abolishes binding (Table 13).

This collection of affinity-tuned fluorescently responsive sensors spans almost four orders of magnitude (from 60 μΜ to 180 mM) and contains candidates suitable both for clinical [e.g. (less than about 2 mM), within (about 2 mM to about 7 mM), or above (greater than about 7 mM) the normal range of human blood] and environmental sensing {e.g., from 60 μΜ ίο 180 mM).

EXAMPLE 7. SENSOR ARRAYS FOR DETECTING A WIDE RANGE OF UREA CONCENTRATIONS

The precision (reciprocal of the error) of individual sensor precision is maximal at the K _& value, and decreases at lower or higher urea concentrations (Marvin et al., 1997, Proc Natl Acad Sci USA, 94, 4366-71). Construction of a high-precision sensor capable of spanning the entire clinical concentration range from 1.8 to 7.1 mM would benefit from combining several sensors together to maintain a high precision level. Candidates for such a high- precision sensor array include csUBP7 186C-Acrylodan and the Ql 14 A, Ql 14Y mutants in this background. Attorney Docket No. 35327-522001 WO

EXAMPLE 8. SENSOR ENGINEERING PHASE 6: DEVICE INTEGRATION

Protein immobilization on solid surfaces is an important step for incorporating biosensors into devices. Immobilization enables (i) spatial localization, (ii) control over the presentation of the sensors to the reader (e.g. by encoding geometries for optical readouts), (iii) selective retention in sample separation procedures. It is advantageous to control the geometry of the protein attachment to the solid surface, in order to minimize perturbation of the fluorescence sensing mechanism. Such constructs fuse an N- or C-terminal protein domain that can mediate site-specific attachment to an appropriately chemically activated surface. For instance, hexa-histidine peptide for metal-mediated immobilization, a hexa- lysine peptide for attachment to amine-reactive groups, or a zinc-finger domain (ZF- QNK)(Smith et al., 2005, Protein Sci, 14, 64-73), or a disulfide-containing truncated zinc finger (pZif)(Smith et al., 2005, Protein Sci, 14, 64-73) at N- or C-termini of the FRS to thiol-reactive groups (FIG. 14). Here we show that site-specific attachment of a robust urea sensor to suitably derivatized agarose beads conserves its emission fluorescence spectral response, binding affinity, and thermostability.

The csUBP7 186C-Acrylodan Ql 14A protein was site-specifically immobilized on agarose beads derivatized with N-hydroxysuccinimide through a carboxy-terminal hexa- lysine fusion tag. This protein also was site-specifically immobilized through its C-terminal hexa-histidine tag on commercially available agarose-coated magnetic beads derivatized with Ni-NTA. The use of magnetic beads affords a straightforward means for holding the beads in place within their respective sensor patches in the sampling cartridge with a magnetic field. The immobilized proteins exhibited a urea titration curve similar to that measured in solution (FIG. 15 A), indicating that immobilization interferes neither with ligand binding nor with the fluorescent signaling mechanism. Furthermore, comparison of protein thermostabilities determined in solution and on beads showed that protein stabilities are not perturbed significantly by immobilization FIG. 15B, C).

The urea-responsive magnetic beads were dried by incubation at 50°C for 20 minutes, using an aqueous ammonium bicarbonate buffer. The stability properties of the sensor are approximately retained up on rehydration (FIG. 15D). The csUBP7-based FRSs therefore are sufficiently robust to be handled at ambient temperatures in a desiccated state, greatly simplifying manufacturing, distribution, and long-term storage conditions. Attorney Docket No. 35327-522001 WO

EXAMPLE 9. CRYSTAL STRUCTURE COORDINATES FOR CSUBP7 UREA- BINDING PROTEIN (MATURE FORM).

Atom positions are provided as Cartesian coordinates, using standard Protein

Databank (PDB) format. ATOM records refer to amino acids (naming is standard three-letter amino acid code); HETATM records refer to non-amino acid atoms.

Column 1 : record type (ATOM or HEATM); column 2: atom number; column 3 atom name (standard naming scheme for amino acids); column 4: residue name (ATOM records), or component name (HETATM records); column 5: chain identifier (A, B, C, ...); column 6: amino acid residue sequence number (ATOM records), or component number (HETATM records); columns 7-9: x,y,z Cartesian positional coordinates; column 10: fractional occupancy (set to 10.0 in listing); column 11 : B-factor (ignored in this listing); column 12: file identifier (ignored in this listing); column 13: line number (same as atom number in this listing).

For heteratom (HETATM) records, the component name (column 4) is as follows: HOH, water

URE, urea

Provided are coordinates for the two protein molecules (chain identifiers A and B) in the asymmetric unit, their bound urea ligand (chain identifiers C and D), and the ordered solvent waters (chain identifier S).

ATOM 9 N ILE A 15 7. .009 63. .200 28. .310 1. .00 0. .00 xxxx 9

ATOM 10 CA ILE A 15 5. .562 63. .372 28. .226 1. .00 0. .00 xxxx 10

ATOM 11 C ILE A 15 4. .922 62. .811 29. .487 1. .00 0. .00 xxxx 11

ATOM 12 O ILE A 15 4. .916 61. .599 29. .697 1. .00 0. .00 xxxx 12

ATOM 13 CB ILE A 15 4. .949 62. .669 27. .002 1. .00 0. .00 xxxx 13

ATOM 14 CGI ILE A 15 5. .395 63. .347 25. .708 1. .00 0. .00 xxxx 14

ATOM 15 CD1 ILE A 15 4. .991 62. .588 24. .464 1. .00 0. .00 xxxx 15

ATOM 16 CG2 ILE A 15 3. .432 62. .692 27. .088 1. .00 0. .00 xxxx 16

ATOM 17 N LYS A 16 4. .390 63. .687 30. .329 1. .00 0. .00 xxxx 17

ATOM 18 CA LYS A 16 3. .826 63. .243 31. .594 1. .00 0. .00 xxxx 18

ATOM 19 C LYS A 16 2. .417 62. .696 31. .411 1. .00 0. .00 xxxx 19

ATOM 20 O LYS A 16 1. .592 63. .281 30. .708 1. .00 0. .00 xxxx 20

ATOM 21 CB LYS A 16 3. .834 64. .381 32. .615 1. .00 0. .00 xxxx 21

ATOM 22 CG LYS A 16 5. .235 64. .766 33. .059 1. .00 0. .00 xxxx 22

ATOM 23 CD LYS A 16 5. .219 65. .820 34. .148 1. .00 0. .00 xxxx 23

ATOM 24 CE LYS A 16 6. .631 66. .108 34. .634 1. .00 0. .00 xxxx 24

ATOM 25 NZ LYS A 16 6. .649 67. .081 35. .759 1. .00 0. .00 xxxx 25

ATOM 26 N VAL A 17 2. .158 61. .560 32. .048 1. .00 0. .00 xxxx 26

ATOM 27 CA VAL A 17 0. .844 60. .939 32. .018 1. .00 0. .00 xxxx 27

ATOM 28 C VAL A 17 0. .393 60. .653 33. .442 1. .00 0. .00 xxxx 28

ATOM 29 O VAL A 17 1. .196 60. .268 34. .292 1. .00 0. .00 xxxx 29

ATOM 30 CB VAL A 17 0. .846 59. .633 31. .199 1. .00 0. .00 xxxx 30

ATOM 31 CGI VAL A 17 1. .297 59. .901 29. .769 1. .00 0. .00 xxxx 31

ATOM 32 CG2 VAL A 17 1. .738 58. .591 31. .858 1. .00 0. .00 xxxx 32

ATOM 33 N GLY A 18 -0. .893 60. .844 33. .701 1. .00 0. .00 xxxx 33

ATOM 34 CA GLY A 18 -1. .421 60. .650 35. .036 1. .00 0. .00 xxxx 34

ATOM 35 C GLY A 18 -1. .924 59. .244 35. .286 1. .00 0. .00 xxxx 35 Attorney Docket No. 35327-522001 WO

ATOM 36 O GLY A 18 -2. .511 58. .613 34. .407 1. .00 0. .00 xxxx 36

ATOM 37 N ILE A 19 -1. .682 58. .753 36. .496 1. .00 0. .00 xxxx 37

ATOM 38 CA ILE A 19 -2. .271 57. .504 36. .953 1. .00 0. .00 xxxx 38

ATOM 39 C ILE A 19 -3. .056 57. .785 38. .225 1. .00 0. .00 xxxx 39

ATOM 40 O ILE A 19 -2. .486 58. .173 39. .245 1. .00 0. .00 xxxx 40

ATOM 41 CB ILE A 19 -1. .206 56. .424 37. .215 1. .00 0. .00 xxxx 41

ATOM 42 CGI ILE A 19 -0. .555 55. .989 35. .900 1. .00 0. .00 xxxx 42

ATOM 43 CD1 ILE A 19 0. .550 54. .968 36. .077 1. .00 0. .00 xxxx 43

ATOM 44 CG2 ILE A 19 -1. .824 55. .229 37. .923 1. .00 0. .00 xxxx 44

ATOM 45 N LEU A 20 -4. .368 57. .592 38. .160 1. .00 0. .00 xxxx 45

ATOM 46 CA LEU A 20 -5. .248 57. .986 39. .250 1. .00 0. .00 xxxx 46

ATOM 47 C LEU A 20 -6. .163 56. .836 39. .659 1. .00 0. .00 xxxx 47

ATOM 48 O LEU A 20 -7. .189 56. .585 39. .026 1. .00 0. .00 xxxx 48

ATOM 49 CB LEU A 20 -6. .068 59. .213 38. .841 1. .00 0. .00 xxxx 49

ATOM 50 CG LEU A 20 -7. .104 59. .755 39. .825 1. .00 0. .00 xxxx 50

ATOM 51 CD1 LEU A 20 -6. .461 60. .063 41. .167 1. .00 0. .00 xxxx 51

ATOM 52 CD2 LEU A 20 -7. .774 60. .995 39. .250 1. .00 0. .00 xxxx 52

ATOM 53 N HIS A 21 -5. .779 56. .143 40. .726 1. .00 0. .00 xxxx 53

ATOM 54 CA HIS A 21 -6. .503 54. .969 41. .195 1. .00 0. .00 xxxx 54

ATOM 55 C HIS A 21 -6. .562 54. .941 42. .716 1. .00 0. .00 xxxx 55

ATOM 56 O HIS A 21 -5. .779 55. .612 43. .389 1. .00 0. .00 xxxx 56

ATOM 57 CB HIS A 21 -5. .846 53. .685 40. .679 1. .00 0. .00 xxxx 57

ATOM 58 CG HIS A 21 -6. .150 53. .380 39. .246 1. .00 0. .00 xxxx 58

ATOM 59 ND1 HIS A 21 -7. .417 53. .060 38. .808 1. .00 0. .00 xxxx 59

ATOM 60 CD2 HIS A 21 -5. .353 53. .342 38. .152 1. .00 0. .00 xxxx 60

ATOM 61 CE1 HIS A 21 -7. .388 52. .839 37. .506 1. .00 0. .00 xxxx 61

ATOM 62 NE2 HIS A 21 -6. .147 53. .005 37. .083 1. .00 0. .00 xxxx 62

ATOM 63 N SER A 22 -7. .498 54. .167 43. .254 1. .00 0. .00 xxxx 63

ATOM 64 CA SER A 22 -7. .576 53. .958 44. .693 1. .00 0. .00 xxxx 64

ATOM 65 C SER A 22 -6. .465 53. .022 45. .154 1. .00 0. .00 xxxx 65

ATOM 66 O SER A 22 -6. .556 51. .808 44. .981 1. .00 0. .00 xxxx 66

ATOM 67 CB SER A 22 -8. .944 53. .395 45. .083 1. .00 0. .00 xxxx 67

ATOM 68 OG SER A 22 -9. .984 54. .262 44. .669 1. .00 0. .00 xxxx 68

ATOM 69 N LEU A 23 -5. .419 53. .593 45. .742 1. .00 0. .00 xxxx 69

ATOM 70 CA LEU A 23 -4. .316 52. .805 46. .279 1. .00 0. .00 xxxx 70

ATOM 71 C LEU A 23 -4. .530 52. .559 47. .765 1. .00 0. .00 xxxx 71

ATOM 72 O LEU A 23 -3. .786 51. .811 48. .399 1. .00 0. .00 xxxx 72

ATOM 73 CB LEU A 23 -2. .985 53. .515 46. .039 1. .00 0. .00 xxxx 73

ATOM 74 CG LEU A 23 -2. .789 54. .016 44. .606 1. .00 0. .00 xxxx 74

ATOM 75 CD1 LEU A 23 -1. .432 54. .684 44. .441 1. .00 0. .00 xxxx 75

ATOM 76 CD2 LEU A 23 -2. .966 52. .881 43. .606 1. .00 0. .00 xxxx 76

ATOM 77 N SER A 24 -5. .558 53. .204 48. .305 1. .00 0. .00 xxxx 77

ATOM 78 CA SER A 24 -5. .993 52. .986 49. .678 1. .00 0. .00 xxxx 78

ATOM 79 C SER A 24 -7. .516 52. .978 49. .725 1. .00 0. .00 xxxx 79

ATOM 80 O SER A 24 -8. .173 53. .438 48. .791 1. .00 0. .00 xxxx 80

ATOM 81 CB SER A 24 -5. .432 54. .062 50. .612 1. .00 0. .00 xxxx 81

ATOM 82 OG SER A 24 -5. .916 55. .350 50. .268 1. .00 0. .00 xxxx 82

ATOM 83 N GLY A 25 -8. .075 52. .453 50. .808 1. .00 0. .00 xxxx 83

ATOM 84 CA GLY A 25 -9. .516 52. .415 50. .965 1. .00 0. .00 xxxx 84

ATOM 85 C GLY A 25 -10. .153 51. .160 50. .401 1. .00 0. .00 xxxx 85

ATOM 86 O GLY A 25 -9. .465 50. .255 49. .928 1. .00 0. .00 xxxx 86

ATOM 87 N THR A 26 -11. .480 51. .119 50. .452 1. .00 0. .00 xxxx 87

ATOM 88 CA THR A 26 -12. .249 49. .925 50. .115 1. .00 0. .00 xxxx 88

ATOM 89 C THR A 26 -12. .073 49. .442 48. .674 1. .00 0. .00 xxxx 89

ATOM 90 O THR A 26 -12. .328 48. .275 48. .378 1. .00 0. .00 xxxx 90

ATOM 91 CB THR A 26 -13. .755 50. .156 50. .366 1. .00 0. .00 xxxx 91

ATOM 92 OG1 THR A 26 -14. .468 48. .924 50. .198 1. .00 0. .00 xxxx 92

ATOM 93 CG2 THR A 26 -14. .310 51. .199 49. .402 1. .00 0. .00 xxxx 93

ATOM 94 N MET A 27 -11. .649 50. .329 47. .777 1. .00 0. .00 xxxx 94

ATOM 95 CA MET A 27 -11. .507 49. .963 46. .367 1. .00 0. .00 xxxx 95

ATOM 96 C MET A 27 -10. .088 49. .523 45. .995 1. .00 0. .00 xxxx 96

ATOM 97 O MET A 27 -9. .841 49. .102 44. .863 1. .00 0. .00 xxxx 97

ATOM 98 CB MET A 27 -11. .933 51. .129 45. .469 1. .00 0. .00 xxxx 98

ATOM 99 CG MET A 27 -13. .423 51. .448 45. .510 1. .00 0. .00 xxxx 99

ATOM 100 SD MET A 27 -14. .467 50. .021 45. .148 1. .00 0. .00 xxxx 100

ATOM 101 CE MET A 27 -13. .779 49. .472 43. .589 1. .00 0. .00 xxxx 101

ATOM 102 N SER A 28 -9. .161 49. .615 46. .944 1. .00 0. .00 xxxx 102 Attorney Docket No. 35327-522001 WO

ATOM 103 CA SER A 28 -7. .758 49. .318 46. .662 1. .00 0. .00 xxxx 103

ATOM 104 C SER A 28 -7. .553 47. .848 46. .303 1. .00 0. .00 xxxx 104

ATOM 105 O SER A 28 -6. .591 47. .498 45. .619 1. .00 0. .00 xxxx 105

ATOM 106 CB SER A 28 -6. .874 49. .698 47. .855 1. .00 0. .00 xxxx 106

ATOM 107 OG SER A 28 -7. .141 48. .879 48. .982 1. .00 0. .00 xxxx 107

ATOM 108 N ILE A 29 -8. .456 46. .993 46. .772 1. .00 0. .00 xxxx 108

ATOM 109 CA ILE A 29 -8. .422 45. .576 46. .429 1. .00 0. .00 xxxx 109

ATOM 110 C ILE A 29 -8. .471 45. .389 44. .915 1. .00 0. .00 xxxx 110

ATOM 111 O ILE A 29 -7. .891 44. .447 44. .370 1. .00 0. .00 xxxx 111

ATOM 112 CB ILE A 29 -9. .592 44. .809 47. .080 1. .00 0. .00 xxxx 112

ATOM 113 CGI ILE A 29 -9. .506 43. .316 46. .757 1. .00 0. .00 xxxx 113

ATOM 114 CG2 ILE A 29 -10. .931 45. .391 46. .637 1. .00 0. .00 xxxx 114

ATOM 115 CD1 ILE A 29 -10. .560 42. .479 47. .455 1. .00 0. .00 xxxx 115

ATOM 116 N SER A 30 -9. .171 46. .300 44. .248 1. .00 0. .00 xxxx 116

ATOM 117 CA SER A 30 -9. .398 46. .216 42. .811 1. .00 0. .00 xxxx 117

ATOM 118 C SER A 30 -8. .435 47. .063 41. .979 1. .00 0. .00 xxxx 118

ATOM 119 O SER A 30 -7. .970 46. .625 40. .929 1. .00 0. .00 xxxx 119

ATOM 120 CB SER A 30 -10. .838 46. .625 42. .487 1. .00 0. .00 xxxx 120

ATOM 121 OG SER A 30 -11. .755 45. .615 42. .868 1. .00 0. .00 xxxx 121

ATOM 122 N GLU A 31 -8. .130 48. .269 42. .450 1. .00 0. .00 xxxx 122

ATOM 123 CA GLU A 31 -7. .507 49. .276 41. .590 1. .00 0. .00 xxxx 123

ATOM 124 C GLU A 31 -5. .979 49. .292 41. .589 1. .00 0. .00 xxxx 124

ATOM 125 O GLU A 31 -5. .371 49. .830 40. .663 1. .00 0. .00 xxxx 125

ATOM 126 CB GLU A 31 -8. .010 50. .668 41. .977 1. .00 0. .00 xxxx 126

ATOM 127 CG GLU A 31 -9. .492 50. .895 41. .723 1. .00 0. .00 xxxx 127

ATOM 128 CD GLU A 31 -9. .875 52. .358 41. .834 1. .00 0. .00 xxxx 128

ATOM 129 OEl GLU A 31 -9. .235 53. .190 41. .157 1. .00 0. .00 xxxx 129

ATOM 130 OE2 GLU A 31 -10. .816 52. .677 42. .592 1. .00 0. .00 xxxx 130

ATOM 131 N VAL A 32 -5. .356 48. .733 42. .622 1. .00 0. .00 xxxx 131

ATOM 132 CA VAL A 32 -3. .898 48. .748 42. .701 1. .00 0. .00 xxxx 132

ATOM 133 C VAL A 32 -3. .287 48. .014 41. .513 1. .00 0. .00 xxxx 133

ATOM 134 O VAL A 32 -2. .295 48. .463 40. .940 1. .00 0. .00 xxxx 134

ATOM 135 CB VAL A 32 -3. .384 48. .117 44. .006 1. .00 0. .00 xxxx 135

ATOM 136 CGI VAL A 32 -1. .884 47. .846 43. .907 1. .00 0. .00 xxxx 136

ATOM 137 CG2 VAL A 32 -3. .694 49. .025 45. .187 1. .00 0. .00 xxxx 137

ATOM 138 N SER A 33 -3. .897 46. .894 41. .138 1. .00 0. .00 xxxx 138

ATOM 139 CA SER A 33 -3. .404 46. .086 40. .028 1. .00 0. .00 xxxx 139

ATOM 140 C SER A 33 -3. .590 46. .794 38. .687 1. .00 0. .00 xxxx 140

ATOM 141 O SER A 33 -2. .910 46. .475 37. .711 1. .00 0. .00 xxxx 141

ATOM 142 CB SER A 33 -4. .104 44. .725 40. .003 1. .00 0. .00 xxxx 142

ATOM 143 OG SER A 33 -5. .508 44. .871 39. .881 1. .00 0. .00 xxxx 143

ATOM 144 N LEU A 34 -4. .508 47. .754 38. .639 1. .00 0. .00 xxxx 144

ATOM 145 CA LEU A 34 -4. .677 48. .567 37. .440 1. .00 0. .00 xxxx 145

ATOM 146 C LEU A 34 -3. .488 49. .509 37. .282 1. .00 0. .00 xxxx 146

ATOM 147 O LEU A 34 -3. .016 49. .743 36. .169 1. .00 0. .00 xxxx 147

ATOM 148 CB LEU A 34 -5. .987 49. .358 37. .486 1. .00 0. .00 xxxx 148

ATOM 149 CG LEU A 34 -7. .274 48. .532 37. .524 1. .00 0. .00 xxxx 149

ATOM 150 CD1 LEU A 34 -8. .487 49. .405 37. .221 1. .00 0. .00 xxxx 150

ATOM 151 CD2 LEU A 34 -7. .193 47. .364 36. .556 1. .00 0. .00 xxxx 151

ATOM 152 N LYS A 35 -3. .018 50. .055 38. .400 1. .00 0. .00 xxxx 152

ATOM 153 CA LYS A 35 -1. .796 50. .850 38. .407 1. .00 0. .00 xxxx 153

ATOM 154 C LYS A 35 -0. .622 50. .026 37. .885 1. .00 0. .00 xxxx 154

ATOM 155 O LYS A 35 0. .201 50. .518 37. .113 1. .00 0. .00 xxxx 155

ATOM 156 CB LYS A 35 -1. .488 51. .370 39. .814 1. .00 0. .00 xxxx 156

ATOM 157 CG LYS A 35 -0. .135 52. .059 39. .927 1. .00 0. .00 xxxx 157

ATOM 158 CD LYS A 35 0. .485 51. .885 41. .303 1. .00 0. .00 xxxx 158

ATOM 159 CE LYS A 35 0. .810 50. .430 41. .589 1. .00 0. .00 xxxx 159

ATOM 160 NZ LYS A 35 1. .679 50. .289 42. .792 1. .00 0. .00 xxxx 160

ATOM 161 N ASP A 36 -0. .553 48. .769 38. .315 1. .00 0. .00 xxxx 161

ATOM 162 CA ASP A 36 0. .507 47. .862 37. .886 1. .00 0. .00 xxxx 162

ATOM 163 C ASP A 36 0. .450 47. .618 36. .382 1. .00 0. .00 xxxx 163

ATOM 164 O ASP A 36 1. .479 47. .614 35. .707 1. .00 0. .00 xxxx 164

ATOM 165 CB ASP A 36 0. .411 46. .528 38. .630 1. .00 0. .00 xxxx 165

ATOM 166 CG ASP A 36 0. .739 46. .654 40. .105 1. .00 0. .00 xxxx 166

ATOM 167 OD1 ASP A 36 1. .432 47. .621 40. .486 1. .00 0. .00 xxxx 167

ATOM 168 OD2 ASP A 36 0. .300 45. .782 40. .883 1. .00 0. .00 xxxx 168

ATOM 169 N ALA A 37 -0. .758 47. .411 35. .866 1. .00 0. .00 xxxx 169 Attorney Docket No. 35327-522001 WO

ATOM 170 CA ALA A 37 -0. .956 47. .171 34. .440 1. .00 0. .00 xxxx 170

ATOM 171 C ALA A 37 -0. .545 48. .383 33. .609 1. .00 0. .00 xxxx 171

ATOM 172 O ALA A 37 0. .132 48. .250 32. .589 1. .00 0. .00 xxxx 172

ATOM 173 CB ALA A 37 -2. .409 46. .808 34. .160 1. .00 0. .00 xxxx 173

ATOM 174 N GLU A 38 -0. .957 49. .565 34. .053 1. .00 0. .00 xxxx 174

ATOM 175 CA GLU A 38 -0. .653 50. .796 33. .335 1. .00 0. .00 xxxx 175

ATOM 176 C GLU A 38 0. .845 51. .091 33. .347 1. .00 0. .00 xxxx 176

ATOM 177 O GLU A 38 1. .400 51. .550 32. .349 1. .00 0. .00 xxxx 177

ATOM 178 CB GLU A 38 -1. .440 51. .965 33. .930 1. .00 0. .00 xxxx 178

ATOM 179 CG GLU A 38 -2. .943 51. .845 33. .720 1. .00 0. .00 xxxx 179

ATOM 180 CD GLU A 38 -3. .751 52. .494 34. .828 1. .00 0. .00 xxxx 180

ATOM 181 OE1 GLU A 38 -3. .141 53. .052 35. .762 1. .00 0. .00 xxxx 181

ATOM 182 OE2 GLU A 38 -4. .998 52. .443 34. .763 1. .00 0. .00 xxxx 182

ATOM 183 N LEU A 39 1. .497 50. .827 34. .475 1. .00 0. .00 xxxx 183

ATOM 184 CA LEU A 39 2. .933 51. .057 34. .584 1. .00 0. .00 xxxx 184

ATOM 185 C LEU A 39 3. .730 50. .078 33. .724 1. .00 0. .00 xxxx 185

ATOM 186 O LEU A 39 4. .786 50. .429 33. .197 1. .00 0. .00 xxxx 186

ATOM 187 CB LEU A 39 3. .389 50. .970 36. .043 1. .00 0. .00 xxxx 187

ATOM 188 CG LEU A 39 3. .026 52. .174 36. .914 1. .00 0. .00 xxxx 188

ATOM 189 CD1 LEU A 39 3. .392 51. .929 38. .369 1. .00 0. .00 xxxx 189

ATOM 190 CD2 LEU A 39 3. .715 53. .425 36. .390 1. .00 0. .00 xxxx 190

ATOM 191 N MET A 40 3. .234 48. .851 33. .587 1. .00 0. .00 xxxx 191

ATOM 192 CA MET A 40 3. .903 47. .866 32. .742 1. .00 0. .00 xxxx 192

ATOM 193 C MET A 40 3. .845 48. .286 31. .277 1. .00 0. .00 xxxx 193

ATOM 194 O MET A 40 4. .851 48. .241 30. .569 1. .00 0. .00 xxxx 194

ATOM 195 CB MET A 40 3. .285 46. .475 32. .910 1. .00 0. .00 xxxx 195

ATOM 196 CG MET A 40 4. .026 45. .399 32. .122 1. .00 0. .00 xxxx 196

ATOM 197 SD MET A 40 3. .421 43. .720 32. .378 1. .00 0. .00 xxxx 197

ATOM 198 CE MET A 40 1. .832 43. .799 31. .556 1. .00 0. .00 xxxx 198

ATOM 199 N ALA A 41 2. .659 48. .694 30. .832 1. .00 0. .00 xxxx 199

ATOM 200 CA ALA A 41 2. .467 49. .167 29. .464 1. .00 0. .00 xxxx 200

ATOM 201 C ALA A 41 3. .364 50. .363 29. .163 1. .00 0. .00 xxxx 201

ATOM 202 O ALA A 41 3. .978 50. .438 28. .098 1. .00 0. .00 xxxx 202

ATOM 203 CB ALA A 41 1. .007 49. .527 29. .225 1. .00 0. .00 xxxx 203

ATOM 204 N ILE A 42 3. .430 51. .298 30. .105 1. .00 0. .00 xxxx 204

ATOM 205 CA ILE A 42 4. .288 52. .469 29. .968 1. .00 0. .00 xxxx 205

ATOM 206 C ILE A 42 5. .761 52. .081 29. .835 1. .00 0. .00 xxxx 206

ATOM 207 O ILE A 42 6. .484 52. .630 29. .002 1. .00 0. .00 xxxx 207

ATOM 208 CB ILE A 42 4. .125 53. .425 31. .165 1. .00 0. .00 xxxx 208

ATOM 209 CGI ILE A 42 2. .734 54. .063 31. .151 1. .00 0. .00 xxxx 209

ATOM 210 CD1 ILE A 42 2. .400 54. .828 32. .416 1. .00 0. .00 xxxx 210

ATOM 211 CG2 ILE A 42 5. .208 54. .494 31. .148 1. .00 0. .00 xxxx 211

ATOM 212 N GLU A 43 6. .202 51. .136 30. .661 1. .00 0. .00 xxxx 212

ATOM 213 CA GLU A 43 7. .585 50. .670 30. .618 1. .00 0. .00 xxxx 213

ATOM 214 C GLU A 43 7. .904 49. .990 29. .291 1. .00 0. .00 xxxx 214

ATOM 215 O GLU A 43 8. .980 50. .189 28. .724 1. .00 0. .00 xxxx 215

ATOM 216 CB GLU A 43 7. .868 49. .711 31. .776 1. .00 0. .00 xxxx 216

ATOM 217 CG GLU A 43 9. .267 49. .117 31. .751 1. .00 0. .00 xxxx 217

ATOM 218 CD GLU A 43 9. .543 48. .214 32. .938 1. .00 0. .00 xxxx 218

ATOM 219 OE1 GLU A 43 8. .833 47. .196 33. .093 1. .00 0. .00 xxxx 219

ATOM 220 OE2 GLU A 43 10. .470 48. .521 33. .716 1. .00 0. .00 xxxx 220

ATOM 221 N GLU A 44 6. .965 49. .184 28. .804 1. .00 0. .00 xxxx 221

ATOM 222 CA GLU A 44 7. .131 48. .492 27. .529 1. .00 0. .00 xxxx 222

ATOM 223 C GLU A 44 7. .279 49. .491 26. .387 1. .00 0. .00 xxxx 223

ATOM 224 O GLU A 44 8. .181 49. .375 25. .557 1. .00 0. .00 xxxx 224

ATOM 225 CB GLU A 44 5. .946 47. .560 27. .258 1. .00 0. .00 xxxx 225

ATOM 226 CG GLU A 44 5. .854 46. .373 28. .199 1. .00 0. .00 xxxx 226

ATOM 227 CD GLU A 44 4. .640 45. .508 27. .926 1. .00 0. .00 xxxx 227

ATOM 228 OE1 GLU A 44 3. .855 45. .850 27. .017 1. .00 0. .00 xxxx 228

ATOM 229 OE2 GLU A 44 4. .470 44. .485 28. .622 1. .00 0. .00 xxxx 229

ATOM 230 N ILE A 45 6. .385 50. .474 26. .355 1. .00 0. .00 xxxx 230

ATOM 231 CA ILE A 45 6. .404 51. .507 25. .325 1. .00 0. .00 xxxx 231

ATOM 232 C ILE A 45 7. .682 52. .345 25. .371 1. .00 0. .00 xxxx 232

ATOM 233 O ILE A 45 8. .240 52. .695 24. .329 1. .00 0. .00 xxxx 233

ATOM 234 CB ILE A 45 5. .181 52. .435 25. .450 1. .00 0. .00 xxxx 234

ATOM 235 CGI ILE A 45 3. .903 51. .671 25. .093 1. .00 0. .00 xxxx 235

ATOM 236 CG2 ILE A 45 5. .340 53. .652 24. .554 1. .00 0. .00 xxxx 236 Attorney Docket No. 35327-522001 WO

ATOM 237 CD1 ILE A 45 2. .625 52. .407 25. .438 1. .00 0. .00 xxxx 237

ATOM 238 N ASN A 46 8. .141 52. .669 26. .576 1. .00 0. .00 xxxx 238

ATOM 239 CA ASN A 46 9. .368 53. .443 26. .735 1. .00 0. .00 xxxx 239

ATOM 240 C ASN A 46 10. .576 52. .680 26. .206 1. .00 0. .00 xxxx 240

ATOM 241 O ASN A 46 11. .473 53. .261 25. .595 1. .00 0. .00 xxxx 241

ATOM 242 CB ASN A 46 9. .585 53. .821 28. .201 1. .00 0. .00 xxxx 242

ATOM 243 CG ASN A 46 8. .711 54. .981 28. .639 1. .00 0. .00 xxxx 243

ATOM 244 OD1 ASN A 46 8. .231 55. .757 27. .812 1. .00 0. .00 xxxx 244

ATOM 245 ND2 ASN A 46 8. .507 55. .111 29. .946 1. .00 0. .00 xxxx 245

ATOM 246 N ASN A 47 10. .589 51. .373 26. .444 1. .00 0. .00 xxxx 246

ATOM 247 CA ASN A 47 11. .667 50. .518 25. .966 1. .00 0. .00 xxxx 247

ATOM 248 C ASN A 47 11. .651 50. .374 24. .447 1. .00 0. .00 xxxx 248

ATOM 249 O ASN A 47 12. .659 50. .009 23. .844 1. .00 0. .00 xxxx 249

ATOM 250 CB ASN A 47 11. .586 49. .139 26. .625 1. .00 0. .00 xxxx 250

ATOM 251 CG ASN A 47 11. .934 49. .177 28. .101 1. .00 0. .00 xxxx 251

ATOM 252 OD1 ASN A 47 12. .550 50. .128 28. .582 1. .00 0. .00 xxxx 252

ATOM 253 ND2 ASN A 47 11. .540 48. .138 28. .828 1. .00 0. .00 xxxx 253

ATOM 254 N ASN A 48 10. .503 50. .655 23. .834 1. .00 0. .00 xxxx 254

ATOM 255 CA ASN A 48 10. .372 50. .589 22. .379 1. .00 0. .00 xxxx 255

ATOM 256 C ASN A 48 10. .612 51. .925 21. .682 1. .00 0. .00 xxxx 256

ATOM 257 O ASN A 48 10. .320 52. .071 20. .496 1. .00 0. .00 xxxx 257

ATOM 258 CB ASN A 48 8. .986 50. .066 21. .994 1. .00 0. .00 xxxx 258

ATOM 259 CG ASN A 48 8. .822 48. .587 22. .271 1. .00 0. .00 xxxx 259

ATOM 260 OD1 ASN A 48 9. .765 47. .914 22. .682 1. .00 0. .00 xxxx 260

ATOM 261 ND2 ASN A 48 7. .618 48. .072 22. .042 1. .00 0. .00 xxxx 261

ATOM 262 N GLY A 49 11. .142 52. .898 22. .416 1. .00 0. .00 xxxx 262

ATOM 263 CA GLY A 49 11. .456 54. .193 21. .840 1. .00 0. .00 xxxx 263

ATOM 264 C GLY A 49 10. .443 55. .271 22. .174 1. .00 0. .00 xxxx 264

ATOM 265 O GLY A 49 10. .497 56. .376 21. .634 1. .00 0. .00 xxxx 265

ATOM 266 N GLY A 50 9. .512 54. .944 23. .064 1. .00 0. .00 xxxx 266

ATOM 267 CA GLY A 50 8. .574 55. .921 23. .588 1. .00 0. .00 xxxx 267

ATOM 268 C GLY A 50 7. .596 56. .483 22. .573 1. .00 0. .00 xxxx 268

ATOM 269 O GLY A 50 7. .202 55. .806 21. .624 1. .00 0. .00 xxxx 269

ATOM 270 N VAL A 51 7. .201 57. .735 22. .782 1. .00 0. .00 xxxx 270

ATOM 271 CA VAL A 51 6. .164 58. .361 21. .974 1. .00 0. .00 xxxx 271

ATOM 272 C VAL A 51 6. .596 59. .734 21. .474 1. .00 0. .00 xxxx 272

ATOM 273 O VAL A 51 6. .963 60. .600 22. .268 1. .00 0. .00 xxxx 273

ATOM 274 CB VAL A 51 4. .847 58. .511 22. .765 1. .00 0. .00 xxxx 274

ATOM 275 CGI VAL A 51 3. .848 59. .351 21. .981 1. .00 0. .00 xxxx 275

ATOM 276 CG2 VAL A 51 4. .268 57. .145 23. .104 1. .00 0. .00 xxxx 276

ATOM 277 N LEU A 52 6. .539 59. .927 20. .158 1. .00 0. .00 xxxx 277

ATOM 278 CA LEU A 52 6. .974 61. .174 19. .534 1. .00 0. .00 xxxx 278

ATOM 279 C LEU A 52 8. .385 61. .565 19. .960 1. .00 0. .00 xxxx 279

ATOM 280 O LEU A 52 8. .683 62. .746 20. .147 1. .00 0. .00 xxxx 280

ATOM 281 CB LEU A 52 5. .994 62. .303 19. .864 1. .00 0. .00 xxxx 281

ATOM 282 CG LEU A 52 4. .555 62. .082 19. .393 1. .00 0. .00 xxxx 282

ATOM 283 CD1 LEU A 52 3. .678 63. .276 19. .742 1. .00 0. .00 xxxx 283

ATOM 284 CD2 LEU A 52 4. .531 61. .806 17. .898 1. .00 0. .00 xxxx 284

ATOM 285 N GLY A 53 9. .241 60. .559 20. .112 1. .00 0. .00 xxxx 285

ATOM 286 CA GLY A 53 10. .626 60. .774 20. .484 1. .00 0. .00 xxxx 286

ATOM 287 C GLY A 53 10. .827 61. .113 21. .948 1. .00 0. .00 xxxx 287

ATOM 288 O GLY A 53 11. .914 61. .526 22. .352 1. .00 0. .00 xxxx 288

ATOM 289 N LYS A 54 9. .776 60. .952 22. .745 1. .00 0. .00 xxxx 289

ATOM 290 CA LYS A 54 9. .863 61. .212 24. .177 1. .00 0. .00 xxxx 290

ATOM 291 C LYS A 54 9. .467 59. .988 24. .995 1. .00 0. .00 xxxx 291

ATOM 292 O LYS A 54 8. .652 59. .176 24. .560 1. .00 0. .00 xxxx 292

ATOM 293 CB LYS A 54 8. .981 62. .405 24. .562 1. .00 0. .00 xxxx 293

ATOM 294 CG LYS A 54 9. .345 63. .704 23. .861 1. .00 0. .00 xxxx 294

ATOM 295 CD LYS A 54 8. .379 64. .821 24. .230 1. .00 0. .00 xxxx 295

ATOM 296 CE LYS A 54 8. .757 66. .125 23. .550 1. .00 0. .00 xxxx 296

ATOM 297 NZ LYS A 54 8. .692 66. .002 22. .069 1. .00 0. .00 xxxx 297

ATOM 298 N LYS A 55 10. .051 59. .860 26. .182 1. .00 0. .00 xxxx 298

ATOM 299 CA LYS A 55 9. .657 58. .811 27. .112 1. .00 0. .00 xxxx 299

ATOM 300 C LYS A 55 8. .435 59. .263 27. .905 1. .00 0. .00 xxxx 300

ATOM 301 O LYS A 55 8. .241 60. .457 28. .130 1. .00 0. .00 xxxx 301

ATOM 302 CB LYS A 55 10. .805 58. .458 28. .059 1. .00 0. .00 xxxx 302

ATOM 303 CG LYS A 55 12. .028 57. .868 27. .372 1. .00 0. .00 xxxx 303 Attorney Docket No. 35327-522001 WO

ATOM 304 CD LYS A 55 11. .638 56. .776 26. .389 1. .00 0. .00 xxxx 304

ATOM 305 CE LYS A 55 12. .860 56. .202 25. .691 1. .00 0. .00 xxxx 305

ATOM 306 NZ LYS A 55 13. .765 55. .509 26. .649 1. .00 0. .00 xxxx 306

ATOM 307 N LEU A 56 7. .612 58. .310 28. .327 1. .00 0. .00 xxxx 307

ATOM 308 CA LEU A 56 6. .458 58. .630 29. .158 1. .00 0. .00 xxxx 308

ATOM 309 C LEU A 56 6. .854 58. .655 30. .629 1. .00 0. .00 xxxx 309

ATOM 310 O LEU A 56 7. .536 57. .751 31. .113 1. .00 0. .00 xxxx 310

ATOM 311 CB LEU A 56 5. .329 57. .623 28. .929 1. .00 0. .00 xxxx 311

ATOM 312 CG LEU A 56 4. .860 57. .430 27. .485 1. .00 0. .00 xxxx 312

ATOM 313 CD1 LEU A 56 3. .893 56. .260 27. .387 1. .00 0. .00 xxxx 313

ATOM 314 CD2 LEU A 56 4. .221 58. .703 26. .953 1. .00 0. .00 xxxx 314

ATOM 315 N GLU A 57 6. .428 59. .697 31. .334 1. .00 0. .00 xxxx 315

ATOM 316 CA GLU A 57 6. .711 59. .822 32. .759 1. .00 0. .00 xxxx 316

ATOM 317 C GLU A 57 5. .419 59. .775 33. .562 1. .00 0. .00 xxxx 317

ATOM 318 O GLU A 57 4. .650 60. .735 33. .564 1. .00 0. .00 xxxx 318

ATOM 319 CB GLU A 57 7. .466 61. .119 33. .059 1. .00 0. .00 xxxx 319

ATOM 320 CG GLU A 57 7. .685 61. .366 34. .546 1. .00 0. .00 xxxx 320

ATOM 321 CD GLU A 57 8. .491 62. .621 34. .824 1. .00 0. .00 xxxx 321

ATOM 322 OE1 GLU A 57 8. .832 63. .340 33. .861 1. .00 0. .00 xxxx 322

ATOM 323 OE2 GLU A 57 8. .784 62. .890 36. .008 1. .00 0. .00 xxxx 323

ATOM 324 N PRO A 58 5. .180 58. .651 34. .250 1. .00 0. .00 xxxx 324

ATOM 325 CA PRO A 58 3. .942 58. .471 35. .014 1. .00 0. .00 xxxx 325

ATOM 326 C PRO A 58 3. .925 59. .272 36. .315 1. .00 0. .00 xxxx 326

ATOM 327 O PRO A 58 4. .907 59. .288 37. .059 1. .00 0. .00 xxxx 327

ATOM 328 CB PRO A 58 3. .924 56. .968 35. .299 1. .00 0. .00 xxxx 328

ATOM 329 CG PRO A 58 5. .360 56. .570 35. .305 1. .00 0. .00 xxxx 329

ATOM 330 CD PRO A 58 6. .067 57. .478 34. .331 1. .00 0. .00 xxxx 330

ATOM 331 N ILE A 59 2. .804 59. .935 36. .574 1. .00 0. .00 xxxx 331

ATOM 332 CA ILE A 59 2. .580 60. .622 37. .838 1. .00 0. .00 xxxx 332

ATOM 333 C ILE A 59 1. .459 59. .909 38. .580 1. .00 0. .00 xxxx 333

ATOM 334 O ILE A 59 0. .296 60. .010 38. .196 1. .00 0. .00 xxxx 334

ATOM 335 CB ILE A 59 2. .211 62. .102 37. .636 1. .00 0. .00 xxxx 335

ATOM 336 CGI ILE A 59 3. .225 62. .788 36. .716 1. .00 0. .00 xxxx 336

ATOM 337 CD1 ILE A 59 4. .639 62. .784 37. .249 1. .00 0. .00 xxxx 337

ATOM 338 CG2 ILE A 59 2. .116 62. .815 38. .978 1. .00 0. .00 xxxx 338

ATOM 339 N VAL A 60 1. .812 59. .184 39. .637 1. .00 0. .00 xxxx 339

ATOM 340 CA VAL A 60 0. .851 58. .332 40. .331 1. .00 0. .00 xxxx 340

ATOM 341 C VAL A 60 0. .192 59. .052 41. .503 1. .00 0. .00 xxxx 341

ATOM 342 O VAL A 60 0. .871 59. .607 42. .369 1. .00 0. .00 xxxx 342

ATOM 343 CB VAL A 60 1. .518 57. .041 40. .844 1. .00 0. .00 xxxx 343

ATOM 344 CGI VAL A 60 0. .527 56. .209 41. .647 1. .00 0. .00 xxxx 344

ATOM 345 CG2 VAL A 60 2. .074 56. .238 39. .682 1. .00 0. .00 xxxx 345

ATOM 346 N GLU A 61 -1. .137 59. .036 41. .521 1. .00 0. .00 xxxx 346

ATOM 347 CA GLU A 61 -1. .906 59. .687 42. .577 1. .00 0. .00 xxxx 347

ATOM 348 C GLU A 61 -2. .923 58. .734 43. .197 1. .00 0. .00 xxxx 348

ATOM 349 O GLU A 61 -3. .594 57. .980 42. .494 1. .00 0. .00 xxxx 349

ATOM 350 CB GLU A 61 -2. .620 60. .928 42. .034 1. .00 0. .00 xxxx 350

ATOM 351 CG GLU A 61 -1. .688 62. .025 41. .546 1. .00 0. .00 xxxx 351

ATOM 352 CD GLU A 61 -0. .884 62. .648 42. .672 1. .00 0. .00 xxxx 352

ATOM 353 OE1 GLU A 61 -1. .361 62. .627 43. .827 1. .00 0. .00 xxxx 353

ATOM 354 OE2 GLU A 61 0. .225 63. .159 42. .403 1. .00 0. .00 xxxx 354

ATOM 355 N ASP A 62 -3. .031 58. .771 44. .520 1. .00 0. .00 xxxx 355

ATOM 356 CA ASP A 62 -4. .011 57. .957 45. .229 1. .00 0. .00 xxxx 356

ATOM 357 C ASP A 62 -5. .384 58. .628 45. .227 1. .00 0. .00 xxxx 357

ATOM 358 O ASP A 62 -5. .537 59. .743 45. .725 1. .00 0. .00 xxxx 358

ATOM 359 CB ASP A 62 -3. .545 57. .697 46. .666 1. .00 0. .00 xxxx 359

ATOM 360 CG ASP A 62 -4. .533 56. .866 47. .464 1. .00 0. .00 xxxx 360

ATOM 361 OD1 ASP A 62 -5. .352 56. .148 46. .852 1. .00 0. .00 xxxx 361

ATOM 362 OD2 ASP A 62 -4. .489 56. .932 48. .711 1. .00 0. .00 xxxx 362

ATOM 363 N GLY A 63 -6. .377 57. .947 44. .661 1. .00 0. .00 xxxx 363

ATOM 364 CA GLY A 63 -7. .744 58. .439 44. .683 1. .00 0. .00 xxxx 364

ATOM 365 C GLY A 63 -8. .432 58. .105 45. .995 1. .00 0. .00 xxxx 365

ATOM 366 O GLY A 63 -9. .473 58. .673 46. .327 1. .00 0. .00 xxxx 366

ATOM 367 N ALA A 64 -7. .847 57. .164 46. .731 1. .00 0. .00 xxxx 367

ATOM 368 CA ALA A 64 -8. .236 56. .869 48. .108 1. .00 0. .00 xxxx 368

ATOM 369 C ALA A 64 -9. .689 56. .422 48. .273 1. .00 0. .00 xxxx 369

ATOM 370 O ALA A 64 -10. .279 56. .626 49. .333 1. .00 0. .00 xxxx 370 Attorney Docket No. 35327-522001 WO

ATOM 371 CB ALA A 64 -7. .969 58. .085 48. .987 1. .00 0. .00 xxxx 371

ATOM 372 N SER A 65 -10. .257 55. .806 47. .239 1. .00 0. .00 xxxx 372

ATOM 373 CA SER A 65 -11. .644 55. .342 47. .289 1. .00 0. .00 xxxx 373

ATOM 374 C SER A 65 -12. .588 56. .471 47. .702 1. .00 0. .00 xxxx 374

ATOM 375 O SER A 65 -13. .645 56. .233 48. .288 1. .00 0. .00 xxxx 375

ATOM 376 CB SER A 65 -11. .784 54. .159 48. .253 1. .00 0. .00 xxxx 376

ATOM 377 OG SER A 65 -10. .884 53. .113 47. .925 1. .00 0. .00 xxxx 377

ATOM 378 N ASP A 66 -12. .193 57. .699 47. .389 1. .00 0. .00 xxxx 378

ATOM 379 CA ASP A 66 -12. .928 58. .884 47. .812 1. .00 0. .00 xxxx 379

ATOM 380 C ASP A 66 -13. .152 59. .797 46. .616 1. .00 0. .00 xxxx 380

ATOM 381 O ASP A 66 -12. .208 60. .362 46. .066 1. .00 0. .00 xxxx 381

ATOM 382 CB ASP A 66 -12. .176 59. .623 48. .921 1. .00 0. .00 xxxx 382

ATOM 383 CG ASP A 66 -12. .942 60. .821 49. .448 1. .00 0. .00 xxxx 383

ATOM 384 OD1 ASP A 66 -13. .940 60. .620 50. .172 1. .00 0. .00 xxxx 384

ATOM 385 OD2 ASP A 66 -12. .546 61. .964 49. .136 1. .00 0. .00 xxxx 385

ATOM 386 N TRP A 67 -14. .410 59. .924 46. .212 1. .00 0. .00 xxxx 386

ATOM 387 CA TRP A 67 -14. .755 60. .579 44. .956 1. .00 0. .00 xxxx 387

ATOM 388 C TRP A 67 -14. .342 62. .052 44. .912 1. .00 0. .00 xxxx 388

ATOM 389 O TRP A 67 -13. .872 62. .528 43. .879 1. .00 0. .00 xxxx 389

ATOM 390 CB TRP A 67 -16. .255 60. .422 44. .687 1. .00 0. .00 xxxx 390

ATOM 391 CG TRP A 67 -16. .792 59. .082 45. .135 1. .00 0. .00 xxxx 391

ATOM 392 CD1 TRP A 67 -17. .999 58. .837 45. .721 1. .00 0. .00 xxxx 392

ATOM 393 CD2 TRP A 67 -16. .122 57. .812 45. .054 1. .00 0. .00 xxxx 393

ATOM 394 NE1 TRP A 67 -18. .130 57. .495 45. .996 1. .00 0. .00 xxxx 394

ATOM 395 CE2 TRP A 67 -16. .990 56. .846 45. .600 1. .00 0. .00 xxxx 395

ATOM 396 CE3 TRP A 67 -14. .874 57. .400 44. .571 1. .00 0. .00 xxxx 396

ATOM 397 CZ2 TRP A 67 -16. .653 55. .498 45. .674 1. .00 0. .00 xxxx 397

ATOM 398 CZ3 TRP A 67 -14. .541 56. .055 44. .649 1. .00 0. .00 xxxx 398

ATOM 399 CH2 TRP A 67 -15. .428 55. .123 45. .195 1. .00 0. .00 xxxx 399

ATOM 400 N PRO A 68 -14. .516 62. .782 46. .026 1. .00 0. .00 xxxx 400

ATOM 401 CA PRO A 68 -13. .989 64. .150 46. .065 1. .00 0. .00 xxxx 401

ATOM 402 C PRO A 68 -12. .471 64. .195 45. .881 1. .00 0. .00 xxxx 402

ATOM 403 O PRO A 68 -11. .958 65. .106 45. .228 1. .00 0. .00 xxxx 403

ATOM 404 CB PRO A 68 -14. .390 64. .638 47. .458 1. .00 0. .00 xxxx 404

ATOM 405 CG PRO A 68 -15. .604 63. .837 47. .792 1. .00 0. .00 xxxx 405

ATOM 406 CD PRO A 68 -15. .345 62. .479 47. .205 1. .00 0. .00 xxxx 406

ATOM 407 N THR A 69 -11. .766 63. .221 46. .450 1. .00 0. .00 xxxx 407

ATOM 408 CA THR A 69 -10. .319 63. .126 46. .283 1. .00 0. .00 xxxx 408

ATOM 409 C THR A 69 -9. .939 62. .873 44. .827 1. .00 0. .00 xxxx 409

ATOM 410 O THR A 69 -8. .962 63. .433 44. .330 1. .00 0. .00 xxxx 410

ATOM 411 CB THR A 69 -9. .717 62. .011 47. .158 1. .00 0. .00 xxxx 411

ATOM 412 OG1 THR A 69 -9. .986 62. .287 48. .537 1. .00 0. .00 xxxx 412

ATOM 413 CG2 THR A 69 -8. .211 61. .929 46. .950 1. .00 0. .00 xxxx 413

ATOM 414 N PHE A 70 -10. .709 62. .025 44. .152 1. .00 0. .00 xxxx 414

ATOM 415 CA PHE A 70 -10. .488 61. .764 42. .732 1. .00 0. .00 xxxx 415

ATOM 416 C PHE A 70 -10. .576 63. .052 41. .923 1. .00 0. .00 xxxx 416

ATOM 417 O PHE A 70 -9. .758 63. .294 41. .036 1. .00 0. .00 xxxx 417

ATOM 418 CB PHE A 70 -11. .495 60. .742 42. .199 1. .00 0. .00 xxxx 418

ATOM 419 CG PHE A 70 -11. .016 59. .320 42. .276 1. .00 0. .00 xxxx 419

ATOM 420 CD1 PHE A 70 -10. .267 58. .775 41. .245 1. .00 0. .00 xxxx 420

ATOM 421 CD2 PHE A 70 -11. .326 58. .523 43. .366 1. .00 0. .00 xxxx 421

ATOM 422 CE1 PHE A 70 -9. .825 57. .469 41. .304 1. .00 0. .00 xxxx 422

ATOM 423 CE2 PHE A 70 -10. .887 57. .213 43. .430 1. .00 0. .00 xxxx 423

ATOM 424 CZ PHE A 70 -10. .137 56. .685 42. .397 1. .00 0. .00 xxxx 424

ATOM 425 N ALA A 71 -11. .574 63. .872 42. .236 1. .00 0. .00 xxxx 425

ATOM 426 CA ALA A 71 -11. .778 65. .133 41. .533 1. .00 0. .00 xxxx 426

ATOM 427 C ALA A 71 -10. .596 66. .077 41. .732 1. .00 0. .00 xxxx 427

ATOM 428 O ALA A 71 -10. .084 66. .651 40. .771 1. .00 0. .00 xxxx 428

ATOM 429 CB ALA A 71 -13. .070 65. .795 41. .997 1. .00 0. .00 xxxx 429

ATOM 430 N GLU A 72 -10. .164 66. .231 42. .979 1. .00 0. .00 xxxx 430

ATOM 431 CA GLU A 72 -9. .043 67. .112 43. .295 1. .00 0. .00 xxxx 431

ATOM 432 C GLU A 72 -7. .742 66. .648 42. .649 1. .00 0. .00 xxxx 432

ATOM 433 O GLU A 72 -6. .979 67. .458 42. .127 1. .00 0. .00 xxxx 433

ATOM 434 CB GLU A 72 -8. .859 67. .219 44. .810 1. .00 0. .00 xxxx 434

ATOM 435 CG GLU A 72 -9. .931 68. .039 45. .501 1. .00 0. .00 xxxx 435

ATOM 436 CD GLU A 72 -10. .079 69. .427 44. .906 1. .00 0. .00 xxxx 436

ATOM 437 OE1 GLU A 72 -9. .060 70. .140 44. .797 1. .00 0. .00 xxxx 437 Attorney Docket No. 35327-522001 WO

ATOM 438 OE2 GLU A 72 -11. .215 69. .802 44. .542 1. .00 0. .00 xxxx 438

ATOM 439 N LYS A 73 -7. .491 65. .343 42. .694 1. .00 0. .00 xxxx 439

ATOM 440 CA LYS A 73 -6. .282 64. .782 42. .100 1. .00 0. .00 xxxx 440

ATOM 441 C LYS A 73 -6. .265 64. .949 40. .584 1. .00 0. .00 xxxx 441

ATOM 442 O LYS A 73 -5. .221 65. .240 40. .000 1. .00 0. .00 xxxx 442

ATOM 443 CB LYS A 73 -6. .133 63. .304 42. .469 1. .00 0. .00 xxxx 443

ATOM 444 CG LYS A 73 -5. .843 63. .075 43. .942 1. .00 0. .00 xxxx 444

ATOM 445 CD LYS A 73 -4. .531 63. .736 44. .336 1. .00 0. .00 xxxx 445

ATOM 446 CE LYS A 73 -4. .183 63. .467 45. .789 1. .00 0. .00 xxxx 446

ATOM 447 NZ LYS A 73 -3. .868 62. .034 46. .028 1. .00 0. .00 xxxx 447

ATOM 448 N ALA A 74 -7. .419 64. .761 39. .951 1. .00 0. .00 xxxx 448

ATOM 449 CA ALA A 74 -7. .535 64. .941 38. .507 1. .00 0. .00 xxxx 449

ATOM 450 C ALA A 74 -7. .225 66. .387 38. .139 1. .00 0. .00 xxxx 450

ATOM 451 O ALA A 74 -6. .584 66. .664 37. .124 1. .00 0. .00 xxxx 451

ATOM 452 CB ALA A 74 -8. .924 64. .551 38. .026 1. .00 0. .00 xxxx 452

ATOM 453 N LYS A 75 -7. .692 67. .304 38. .979 1. .00 0. .00 xxxx 453

ATOM 454 CA LYS A 75 -7. .459 68. .728 38. .783 1. .00 0. .00 xxxx 454

ATOM 455 C LYS A 75 -5. .971 69. .060 38. .875 1. .00 0. .00 xxxx 455

ATOM 456 O LYS A 75 -5. .435 69. .780 38. .033 1. .00 0. .00 xxxx 456

ATOM 457 CB LYS A 75 -8. .254 69. .535 39. .811 1. .00 0. .00 xxxx 457

ATOM 458 CG LYS A 75 -8. .206 71. .040 39. .614 1. .00 0. .00 xxxx 458

ATOM 459 CD LYS A 75 -9. .152 71. .736 40. .581 1. .00 0. .00 xxxx 459

ATOM 460 CE LYS A 75 -9. .167 73. .240 40. .368 1. .00 0. .00 xxxx 460

ATOM 461 NZ LYS A 75 -10. .122 73. .916 41. .292 1. .00 0. .00 xxxx 461

ATOM 462 N LYS A 76 -5. .310 68. .533 39. .902 1. .00 0. .00 xxxx 462

ATOM 463 CA LYS A 76 -3. .871 68. .722 40. .068 1. .00 0. .00 xxxx 463

ATOM 464 C LYS A 76 -3. .085 68. .143 38. .893 1. .00 0. .00 xxxx 464

ATOM 465 O LYS A 76 -2. .166 68. .780 38. .377 1. .00 0. .00 xxxx 465

ATOM 466 CB LYS A 76 -3. .387 68. .085 41. .372 1. .00 0. .00 xxxx 466

ATOM 467 CG LYS A 76 -1. .871 68. .010 41. .481 1. .00 0. .00 xxxx 467

ATOM 468 CD LYS A 76 -1. .428 67. .349 42. .774 1. .00 0. .00 xxxx 468

ATOM 469 CE LYS A 76 -0. .726 66. .026 42. .507 1. .00 0. .00 xxxx 469

ATOM 470 NZ LYS A 76 0. .521 66. .197 41. .707 1. .00 0. .00 xxxx 470

ATOM 471 N LEU A 77 -3. .448 66. .931 38. .482 1. .00 0. .00 xxxx 471

ATOM 472 CA LEU A 77 -2. .756 66. .245 37. .396 1. .00 0. .00 xxxx 472

ATOM 473 C LEU A 77 -2. .831 67. .021 36. .083 1. .00 0. .00 xxxx 473

ATOM 474 O LEU A 77 -1. .859 67. .074 35. .330 1. .00 0. .00 xxxx 474

ATOM 475 CB LEU A 77 -3. .331 64. .839 37. .205 1. .00 0. .00 xxxx 475

ATOM 476 CG LEU A 77 -2. .867 63. .794 38. .223 1. .00 0. .00 xxxx 476

ATOM 477 CD1 LEU A 77 -3. .691 62. .523 38. .112 1. .00 0. .00 xxxx 477

ATOM 478 CD2 LEU A 77 -1. .387 63. .494 38. .037 1. .00 0. .00 xxxx 478

ATOM 479 N LEU A 78 -3. .986 67. .621 35. .813 1. .00 0. .00 xxxx 479

ATOM 480 CA LEU A 78 -4. .183 68. .369 34. .576 1. .00 0. .00 xxxx 480

ATOM 481 C LEU A 78 -3. .627 69. .790 34. .653 1. .00 0. .00 xxxx 481

ATOM 482 O LEU A 78 -3. .013 70. .276 33. .703 1. .00 0. .00 xxxx 482

ATOM 483 CB LEU A 78 -5. .669 68. .414 34. .209 1. .00 0. .00 xxxx 483

ATOM 484 CG LEU A 78 -6. .311 67. .077 33. .830 1. .00 0. .00 xxxx 484

ATOM 485 CD1 LEU A 78 -7. .799 67. .250 33. .566 1. .00 0. .00 xxxx 485

ATOM 486 CD2 LEU A 78 -5. .615 66. .468 32. .620 1. .00 0. .00 xxxx 486

ATOM 487 N GLN A 79 -3. .842 70. .451 35. .786 1. .00 0. .00 xxxx 487

ATOM 488 CA GLN A 79 -3. .524 71. .872 35. .913 1. .00 0. .00 xxxx 488

ATOM 489 C GLN A 79 -2. .118 72. .151 36. .446 1. .00 0. .00 xxxx 489

ATOM 490 O GLN A 79 -1. .468 73. .103 36. .015 1. .00 0. .00 xxxx 490

ATOM 491 CB GLN A 79 -4. .557 72. .553 36. .814 1. .00 0. .00 xxxx 491

ATOM 492 CG GLN A 79 -5. .963 72. .564 36. .236 1. .00 0. .00 xxxx 492

ATOM 493 CD GLN A 79 -6. .935 73. .357 37. .084 1. .00 0. .00 xxxx 493

ATOM 494 OE1 GLN A 79 -6. .573 73. .880 38. .137 1. .00 0. .00 xxxx 494

ATOM 495 NE2 GLN A 79 -8. .180 73. .450 36. .629 1. .00 0. .00 xxxx 495

ATOM 496 N LYS A 80 -1. .647 71. .326 37. .374 1. .00 0. .00 xxxx 496

ATOM 497 CA LYS A 80 -0. .332 71. .538 37. .972 1. .00 0. .00 xxxx 497

ATOM 498 C LYS A 80 0. .742 70. .687 37. .303 1. .00 0. .00 xxxx 498

ATOM 499 O LYS A 80 1. .794 71. .193 36. .909 1. .00 0. .00 xxxx 499

ATOM 500 CB LYS A 80 -0. .374 71. .242 39. .472 1. .00 0. .00 xxxx 500

ATOM 501 CG LYS A 80 -1. .262 72. .189 40. .260 1. .00 0. .00 xxxx 501

ATOM 502 CD LYS A 80 -0. .718 73. .608 40. .215 1. .00 0. .00 xxxx 502

ATOM 503 CE LYS A 80 -1. .543 74. .548 41. .078 1. .00 0. .00 xxxx 503

ATOM 504 NZ LYS A 80 -1. .533 74. .145 42. .512 1. .00 0. .00 xxxx 504 Attorney Docket No. 35327-522001 WO

ATOM 505 N ASP A 81 0. .474 69. .392 37. .180 1. .00 0. .00 xxxx 505

ATOM 506 CA ASP A 81 1. .423 68. .479 36. .560 1. .00 0. .00 xxxx 506

ATOM 507 C ASP A 81 1. .358 68. .595 35. .043 1. .00 0. .00 xxxx 507

ATOM 508 O ASP A 81 2. .311 68. .249 34. .343 1. .00 0. .00 xxxx 508

ATOM 509 CB ASP A 81 1. .145 67. .040 36. .997 1. .00 0. .00 xxxx 509

ATOM 510 CG ASP A 81 1. .313 66. .844 38. .491 1. .00 0. .00 xxxx 510

ATOM 511 OD1 ASP A 81 2. .389 67. .192 39. .020 1. .00 0. .00 xxxx 511

ATOM 512 OD2 ASP A 81 0. .366 66. .348 39. .136 1. .00 0. .00 xxxx 512

ATOM 513 N LYS A 82 0. .226 69. .091 34. .550 1. .00 0. .00 xxxx 513

ATOM 514 CA LYS A 82 -0. .001 69. .278 33. .120 1. .00 0. .00 xxxx 514

ATOM 515 C LYS A 82 0. .251 67. .997 32. .332 1. .00 0. .00 xxxx 515

ATOM 516 O LYS A 82 0. .975 67. .998 31. .337 1. .00 0. .00 xxxx 516

ATOM 517 CB LYS A 82 0. .876 70. .411 32. .585 1. .00 0. .00 xxxx 517

ATOM 518 CG LYS A 82 0. .522 71. .777 33. .153 1. .00 0. .00 xxxx 518

ATOM 519 CD LYS A 82 1. .492 72. .846 32. .682 1. .00 0. .00 xxxx 519

ATOM 520 CE LYS A 82 1. .200 74. .183 33. .345 1. .00 0. .00 xxxx 520

ATOM 521 NZ LYS A 82 -0. .238 74. .553 33. .236 1. .00 0. .00 xxxx 521

ATOM 522 N VAL A 83 -0. .353 66. .904 32. .785 1. .00 0. .00 xxxx 522

ATOM 523 CA VAL A 83 -0. .227 65. .629 32. .095 1. .00 0. .00 xxxx 523

ATOM 524 C VAL A 83 -0. .980 65. .670 30. .768 1. .00 0. .00 xxxx 524

ATOM 525 O VAL A 83 -1. .882 66. .486 30. .581 1. .00 0. .00 xxxx 525

ATOM 526 CB VAL A 83 -0. .756 64. .466 32. .955 1. .00 0. .00 xxxx 526

ATOM 527 CGI VAL A 83 -0. .005 64. .401 34. .282 1. .00 0. .00 xxxx 527

ATOM 528 CG2 VAL A 83 -2. .249 64. .617 33. .187 1. .00 0. .00 xxxx 528

ATOM 529 N ALA A 84 -0. .609 64. .784 29. .851 1. .00 0. .00 xxxx 529

ATOM 530 CA ALA A 84 -1. .257 64. .723 28. .547 1. .00 0. .00 xxxx 530

ATOM 531 C ALA A 84 -2. .525 63. .884 28. .619 1. .00 0. .00 xxxx 531

ATOM 532 O ALA A 84 -3. .400 63. .987 27. .760 1. .00 0. .00 xxxx 532

ATOM 533 CB ALA A 84 -0. .305 64. .157 27. .505 1. .00 0. .00 xxxx 533

ATOM 534 N VAL A 85 -2. .615 63. .054 29. .650 1. .00 0. .00 xxxx 534

ATOM 535 CA VAL A 85 -3. .725 62. .122 29. .788 1. .00 0. .00 xxxx 535

ATOM 536 C VAL A 85 -3. .748 61. .525 31. .189 1. .00 0. .00 xxxx 536

ATOM 537 O VAL A 85 -2. .717 61. .453 31. .859 1. .00 0. .00 xxxx 537

ATOM 538 CB VAL A 85 -3. .639 60. .983 28. .748 1. .00 0. .00 xxxx 538

ATOM 539 CGI VAL A 85 -2. .373 60. .169 28. .960 1. .00 0. .00 xxxx 539

ATOM 540 CG2 VAL A 85 -4. .870 60. .090 28. .822 1. .00 0. .00 xxxx 540

ATOM 541 N ILE A 86 -4. .929 61. .108 31. .630 1. .00 0. .00 xxxx 541

ATOM 542 CA ILE A 86 -5. .068 60. .401 32. .894 1. .00 0. .00 xxxx 542

ATOM 543 C ILE A 86 -5. .610 58. .998 32. .668 1. .00 0. .00 xxxx 543

ATOM 544 O ILE A 86 -6. .639 58. .820 32. .016 1. .00 0. .00 xxxx 544

ATOM 545 CB ILE A 86 -6. .007 61. .142 33. .866 1. .00 0. .00 xxxx 545

ATOM 546 CGI ILE A 86 -5. .464 62. .537 34. .185 1. .00 0. .00 xxxx 546

ATOM 547 CG2 ILE A 86 -6. .191 60. .332 35. .141 1. .00 0. .00 xxxx 547

ATOM 548 CD1 ILE A 86 -6. .411 63. .386 35. .011 1. .00 0. .00 xxxx 548

ATOM 549 N PHE A 87 -4. .905 58. .004 33. .197 1. .00 0. .00 xxxx 549

ATOM 550 CA PHE A 87 -5. .420 56. .642 33. .252 1. .00 0. .00 xxxx 550

ATOM 551 C PHE A 87 -5. .904 56. .363 34. .674 1. .00 0. .00 xxxx 551

ATOM 552 O PHE A 87 -5. .130 56. .486 35. .622 1. .00 0. .00 xxxx 552

ATOM 553 CB PHE A 87 -4. .343 55. .632 32. .843 1. .00 0. .00 xxxx 553

ATOM 554 CG PHE A 87 -3. .706 55. .926 31. .512 1. .00 0. .00 xxxx 554

ATOM 555 CD1 PHE A 87 -4. .340 55. .579 30. .331 1. .00 0. .00 xxxx 555

ATOM 556 CD2 PHE A 87 -2. .471 56. .549 31. .446 1. .00 0. .00 xxxx 556

ATOM 557 CE1 PHE A 87 -3. .753 55. .850 29. .106 1. .00 0. .00 xxxx 557

ATOM 558 CE2 PHE A 87 -1. .878 56. .822 30. .225 1. .00 0. .00 xxxx 558

ATOM 559 CZ PHE A 87 -2. .521 56. .472 29. .054 1. .00 0. .00 xxxx 559

ATOM 560 N GLY A 88 -7. .169 55. .992 34. .839 1. .00 0. .00 xxxx 560

ATOM 561 CA GLY A 88 -7. .660 55. .729 36. .181 1. .00 0. .00 xxxx 561

ATOM 562 C GLY A 88 -9. .158 55. .646 36. .399 1. .00 0. .00 xxxx 562

ATOM 563 O GLY A 88 -9. .941 55. .580 35. .450 1. .00 0. .00 xxxx 563

ATOM 564 N ALA A 89 -9. .533 55. .640 37. .678 1. .00 0. .00 xxxx 564

ATOM 565 CA ALA A 89 -10. .914 55. .502 38. .142 1. .00 0. .00 xxxx 565

ATOM 566 C ALA A 89 -11. .406 54. .060 38. .039 1. .00 0. .00 xxxx 566

ATOM 567 O ALA A 89 -10. .868 53. .259 37. .274 1. .00 0. .00 xxxx 567

ATOM 568 CB ALA A 89 -11. .841 56. .439 37. .372 1. .00 0. .00 xxxx 568

ATOM 569 N TRP A 90 -12. .423 53. .739 38. .832 1. .00 0. .00 xxxx 569

ATOM 570 CA TRP A 90 -13. .065 52. .431 38. .784 1. .00 0. .00 xxxx 570

ATOM 571 C TRP A 90 -14. .567 52. .602 38. .973 1. .00 0. .00 xxxx 571 Attorney Docket No. 35327-522001 WO

ATOM 572 O TRP A 90 -15. .344 52. .381 38. .045 1. .00 0. .00 xxxx 572

ATOM 573 CB TRP A 90 -12. .486 51. .490 39. .853 1. .00 0. .00 xxxx 573

ATOM 574 CG TRP A 90 -13. .174 50. .143 39. .939 1. .00 0. .00 xxxx 574

ATOM 575 CD1 TRP A 90 -14. .453 49. .894 40. .354 1. .00 0. .00 xxxx 575

ATOM 576 CD2 TRP A 90 -12. .612 48. .866 39. .600 1. .00 0. .00 xxxx 576

ATOM 577 NE1 TRP A 90 -14. .720 48. .549 40. .291 1. .00 0. .00 xxxx 577

ATOM 578 CE2 TRP A 90 -13. .608 47. .895 39. .834 1. .00 0. .00 xxxx 578

ATOM 579 CE3 TRP A 90 -11. .364 48. .450 39. .124 1. .00 0. .00 xxxx 579

ATOM 580 CZ2 TRP A 90 -13. .395 46. .536 39. .606 1. .00 0. .00 xxxx 580

ATOM 581 CZ3 TRP A 90 -11. .155 47. .100 38. .897 1. .00 0. .00 xxxx 581

ATOM 582 CH2 TRP A 90 -12. .165 46. .159 39. .139 1. .00 0. .00 xxxx 582

ATOM 583 N THR A 91 -14. .974 52. .998 40. .177 1. .00 0. .00 xxxx 583

ATOM 584 CA THR A 91 -16. .388 53. .216 40. .450 1. .00 0. .00 xxxx 584

ATOM 585 C THR A 91 -16. .904 54. .349 39. .574 1. .00 0. .00 xxxx 585

ATOM 586 O THR A 91 -16. .183 55. .310 39. .301 1. .00 0. .00 xxxx 586

ATOM 587 CB THR A 91 -16. .650 53. .555 41. .930 1. .00 0. .00 xxxx 587

ATOM 588 OG1 THR A 91 -16. .068 54. .825 42. .246 1. .00 0. .00 xxxx 588

ATOM 589 CG2 THR A 91 -16. .068 52. .483 42. .843 1. .00 0. .00 xxxx 589

ATOM 590 N SER A 92 -18. .156 54. .240 39. .145 1. .00 0. .00 xxxx 590

ATOM 591 CA SER A 92 -18. .775 55. .281 38. .339 1. .00 0. .00 xxxx 591

ATOM 592 C SER A 92 -18. .872 56. .580 39. .131 1. .00 0. .00 xxxx 592

ATOM 593 O SER A 92 -18. .956 57. .665 38. .556 1. .00 0. .00 xxxx 593

ATOM 594 CB SER A 92 -20. .158 54. .838 37. .862 1. .00 0. .00 xxxx 594

ATOM 595 OG SER A 92 -20. .052 53. .751 36. .960 1. .00 0. .00 xxxx 595

ATOM 596 N ALA A 93 -18. .855 56. .460 40. .456 1. .00 0. .00 xxxx 596

ATOM 597 CA ALA A 93 -18. .814 57. .625 41. .331 1. .00 0. .00 xxxx 597

ATOM 598 C ALA A 93 -17. .519 58. .400 41. .124 1. .00 0. .00 xxxx 598

ATOM 599 O ALA A 93 -17. .528 59. .626 41. .002 1. .00 0. .00 xxxx 599

ATOM 600 CB ALA A 93 -18. .956 57. .204 42. .790 1. .00 0. .00 xxxx 600

ATOM 601 N SER A 94 -16. .404 57. .677 41. .080 1. .00 0. .00 xxxx 601

ATOM 602 CA SER A 94 -15. .100 58. .295 40. .870 1. .00 0. .00 xxxx 602

ATOM 603 C SER A 94 -14. .969 58. .852 39. .453 1. .00 0. .00 xxxx 603

ATOM 604 O SER A 94 -14. .401 59. .926 39. .254 1. .00 0. .00 xxxx 604

ATOM 605 CB SER A 94 -13. .975 57. .293 41. .153 1. .00 0. .00 xxxx 605

ATOM 606 OG SER A 94 -13. .952 56. .252 40. .193 1. .00 0. .00 xxxx 606

ATOM 607 N ARG A 95 -15. .492 58. .121 38. .472 1. .00 0. .00 xxxx 607

ATOM 608 CA ARG A 95 -15. .432 58. .572 37. .085 1. .00 0. .00 xxxx 608

ATOM 609 C ARG A 95 -16. .239 59. .853 36. .901 1. .00 0. .00 xxxx 609

ATOM 610 O ARG A 95 -15. .793 60. .793 36. .242 1. .00 0. .00 xxxx 610

ATOM 611 CB ARG A 95 -15. .945 57. .495 36. .126 1. .00 0. .00 xxxx 611

ATOM 612 CG ARG A 95 -15. .678 57. .820 34. .659 1. .00 0. .00 xxxx 612

ATOM 613 CD ARG A 95 -16. .442 56. .911 33. .702 1. .00 0. .00 xxxx 613

ATOM 614 NE ARG A 95 -17. .890 57. .088 33. .800 1. .00 0. .00 xxxx 614

ATOM 615 CZ ARG A 95 -18. .702 56. .256 34. .442 1. .00 0. .00 xxxx 615

ATOM 616 NH1 ARG A 95 -18. .213 55. .180 35. .040 1. .00 0. .00 xxxx 616

ATOM 617 NH2 ARG A 95 -20. .006 56. .498 34. .480 1. .00 0. .00 xxxx 617

ATOM 618 N LYS A 96 -17. .432 59. .881 37. .487 1. .00 0. .00 xxxx 618

ATOM 619 CA LYS A 96 -18. .325 61. .025 37. .350 1. .00 0. .00 xxxx 619

ATOM 620 C LYS A 96 -17. .824 62. .235 38. .130 1. .00 0. .00 xxxx 620

ATOM 621 O LYS A 96 -18. .209 63. .368 37. .843 1. .00 0. .00 xxxx 621

ATOM 622 CB LYS A 96 -19. .738 60. .654 37. .801 1. .00 0. .00 xxxx 622

ATOM 623 CG LYS A 96 -20. .516 59. .852 36. .768 1. .00 0. .00 xxxx 623

ATOM 624 CD LYS A 96 -21. .931 59. .556 37. .234 1. .00 0. .00 xxxx 624

ATOM 625 CE LYS A 96 -22. .659 58. .663 36. .243 1. .00 0. .00 xxxx 625

ATOM 626 NZ LYS A 96 -22. .860 59. .339 34. .929 1. .00 0. .00 xxxx 626

ATOM 627 N ALA A 97 -16. .974 61. .993 39. .122 1. .00 0. .00 xxxx 627

ATOM 628 CA ALA A 97 -16. .320 63. .081 39. .840 1. .00 0. .00 xxxx 628

ATOM 629 C ALA A 97 -15. .213 63. .679 38. .977 1. .00 0. .00 xxxx 629

ATOM 630 O ALA A 97 -14. .947 64. .881 39. .022 1. .00 0. .00 xxxx 630

ATOM 631 CB ALA A 97 -15. .766 62. .591 41. .166 1. .00 0. .00 xxxx 631

ATOM 632 N VAL A 98 -14. .571 62. .821 38. .191 1. .00 0. .00 xxxx 632

ATOM 633 CA VAL A 98 -13. .494 63. .233 37. .300 1. .00 0. .00 xxxx 633

ATOM 634 C VAL A 98 -14. .030 63. .852 36. .011 1. .00 0. .00 xxxx 634

ATOM 635 O VAL A 98 -13. .383 64. .713 35. .412 1. .00 0. .00 xxxx 635

ATOM 636 CB VAL A 98 -12. .584 62. .040 36. .944 1. .00 0. .00 xxxx 636

ATOM 637 CGI VAL A 98 -11. .600 62. .422 35. .846 1. .00 0. .00 xxxx 637

ATOM 638 CG2 VAL A 98 -11. .851 61. .541 38. .185 1. .00 0. .00 xxxx 638 Attorney Docket No. 35327-522001 WO

ATOM 639 N LEU A 99 -15. .212 63. .406 35. .594 1. .00 0. .00 xxxx 639

ATOM 640 CA LEU A 99 -15. .792 63. .798 34. .310 1. .00 0. .00 xxxx 640

ATOM 641 C LEU A 99 -15. .823 65. .314 34. .091 1. .00 0. .00 xxxx 641

ATOM 642 O LEU A 99 -15. .362 65. .800 33. .058 1. .00 0. .00 xxxx 642

ATOM 643 CB LEU A 99 -17. .206 63. .224 34. .176 1. .00 0. .00 xxxx 643

ATOM 644 CG LEU A 99 -17. .940 63. .439 32. .847 1. .00 0. .00 xxxx 644

ATOM 645 CD1 LEU A 99 -19. .041 62. .404 32. .676 1. .00 0. .00 xxxx 645

ATOM 646 CD2 LEU A 99 -18. .517 64. .841 32. .745 1. .00 0. .00 xxxx 646

ATOM 647 N PRO A 100 -16. .370 66. .068 35. .056 1. .00 0. .00 xxxx 647

ATOM 648 CA PRO A 100 -16. .426 67. .525 34. .888 1. .00 0. .00 xxxx 648

ATOM 649 C PRO A 100 -15. .041 68. .169 34. .835 1. .00 0. .00 xxxx 649

ATOM 650 O PRO A 100 -14. .880 69. .217 34. .208 1. .00 0. .00 xxxx 650

ATOM 651 CB PRO A 100 -17. .203 67. .994 36. .125 1. .00 0. .00 xxxx 651

ATOM 652 CG PRO A 100 -17. .051 66. .889 37. .116 1. .00 0. .00 xxxx 652

ATOM 653 CD PRO A 100 -17. .002 65. .632 36. .311 1. .00 0. .00 xxxx 653

ATOM 654 N VAL A 101 -14. .055 67. .546 35. .472 1. .00 0. .00 xxxx 654

ATOM 655 CA VAL A 101 -12. .702 68. .091 35. .480 1. .00 0. .00 xxxx 655

ATOM 656 C VAL A 101 -12. .028 67. .972 34. .113 1. .00 0. .00 xxxx 656

ATOM 657 O VAL A 101 -11. .437 68. .935 33. .625 1. .00 0. .00 xxxx 657

ATOM 658 CB VAL A 101 -11. .818 67. .397 36. .533 1. .00 0. .00 xxxx 658

ATOM 659 CGI VAL A 101 -10. .416 67. .991 36. .518 1. .00 0. .00 xxxx 659

ATOM 660 CG2 VAL A 101 -12. .442 67. .519 37. .916 1. .00 0. .00 xxxx 660

ATOM 661 N VAL A 102 -12. .117 66. .798 33. .494 1. .00 0. .00 xxxx 661

ATOM 662 CA VAL A 102 -11. .510 66. .597 32. .181 1. .00 0. .00 xxxx 662

ATOM 663 C VAL A 102 -12. .256 67. .371 31. .098 1. .00 0. .00 xxxx 663

ATOM 664 O VAL A 102 -11. .656 67. .824 30. .123 1. .00 0. .00 xxxx 664

ATOM 665 CB VAL A 102 -11. .460 65. .103 31. .790 1. .00 0. .00 xxxx 665

ATOM 666 CGI VAL A 102 -10. .355 64. .385 32. .555 1. .00 0. .00 xxxx 666

ATOM 667 CG2 VAL A 102 -12. .816 64. .441 32. .014 1. .00 0. .00 xxxx 667

ATOM 668 N GLU A 103 -13. .565 67. .524 31. .268 1. .00 0. .00 xxxx 668

ATOM 669 CA GLU A 103 -14. .356 68. .281 30. .308 1. .00 0. .00 xxxx 669

ATOM 670 C GLU A 103 -14. .040 69. .775 30. .387 1. .00 0. .00 xxxx 670

ATOM 671 O GLU A 103 -13. .872 70. .432 29. .364 1. .00 0. .00 xxxx 671

ATOM 672 CB GLU A 103 -15. .851 68. .037 30. .525 1. .00 0. .00 xxxx 672

ATOM 673 CG GLU A 103 -16. .314 66. .655 30. .082 1. .00 0. .00 xxxx 673

ATOM 674 CD GLU A 103 -17. .819 66. .556 29. .929 1. .00 0. .00 xxxx 674

ATOM 675 OE1 GLU A 103 -18. .519 67. .542 30. .246 1. .00 0. .00 xxxx 675

ATOM 676 OE2 GLU A 103 -18. .304 65. .493 29. .486 1. .00 0. .00 xxxx 676

ATOM 677 N GLU A 104 -13. .952 70. .313 31. .598 1. .00 0. .00 xxxx 677

ATOM 678 CA GLU A 104 -13. .697 71. .742 31. .760 1. .00 0. .00 xxxx 678

ATOM 679 C GLU A 104 -12. .282 72. .114 31. .314 1. .00 0. .00 xxxx 679

ATOM 680 O GLU A 104 -12. .057 73. .201 30. .782 1. .00 0. .00 xxxx 680

ATOM 681 CB GLU A 104 -13. .932 72. .173 33. .208 1. .00 0. .00 xxxx 681

ATOM 682 CG GLU A 104 -14. .016 73. .681 33. .384 1. .00 0. .00 xxxx 682

ATOM 683 CD GLU A 104 -14. .200 74. .096 34. .829 1. .00 0. .00 xxxx 683

ATOM 684 OE1 GLU A 104 -13. .909 73. .278 35. .726 1. .00 0. .00 xxxx 684

ATOM 685 OE2 GLU A 104 -14. .639 75. .241 35. .068 1. .00 0. .00 xxxx 685

ATOM 686 N ASN A 105 -11. .332 71. .211 31. .536 1. .00 0. .00 xxxx 686

ATOM 687 CA ASN A 105 -9. .946 71. .456 31. .151 1. .00 0. .00 xxxx 687

ATOM 688 C ASN A 105 -9. .622 70. .888 29. .774 1. .00 0. .00 xxxx 688

ATOM 689 O ASN A 105 -8. .492 71. .002 29. .298 1. .00 0. .00 xxxx 689

ATOM 690 CB ASN A 105 -8. .990 70. .861 32. .187 1. .00 0. .00 xxxx 690

ATOM 691 CG ASN A 105 -9. .072 71. .563 33. .527 1. .00 0. .00 xxxx 691

ATOM 692 OD1 ASN A 105 -8. .410 72. .576 33. .750 1. .00 0. .00 xxxx 692

ATOM 693 ND2 ASN A 105 -9. .882 71. .023 34. .430 1. .00 0. .00 xxxx 693

ATOM 694 N ASN A 106 -10. .626 70. .293 29. .136 1. .00 0. .00 xxxx 694

ATOM 695 CA ASN A 106 -10. .432 69. .558 27. .890 1. .00 0. .00 xxxx 695

ATOM 696 C ASN A 106 -9. .271 68. .570 27. .988 1. .00 0. .00 xxxx 696

ATOM 697 O ASN A 106 -8. .399 68. .527 27. .121 1. .00 0. .00 xxxx 697

ATOM 698 CB ASN A 106 -10. .202 70. .524 26. .726 1. .00 0. .00 xxxx 698

ATOM 699 CG ASN A 106 -10. .392 69. .862 25. .371 1. .00 0. .00 xxxx 699

ATOM 700 OD1 ASN A 106 -11. .155 68. .904 25. .236 1. .00 0. .00 xxxx 700

ATOM 701 ND2 ASN A 106 -9. .698 70. .373 24. .360 1. .00 0. .00 xxxx 701

ATOM 702 N GLY A 107 -9. .263 67. .786 29. .059 1. .00 0. .00 xxxx 702

ATOM 703 CA GLY A 107 -8. .279 66. .734 29. .219 1. .00 0. .00 xxxx 703

ATOM 704 C GLY A 107 -8. .853 65. .413 28. .755 1. .00 0. .00 xxxx 704

ATOM 705 O GLY A 107 -9. .961 65. .362 28. .222 1. .00 0. .00 xxxx 705 Attorney Docket No. 35327-522001 WO

ATOM 706 N LEU A 108 -8. .102 64. .337 28. .958 1. .00 0. .00 xxxx 706

ATOM 707 CA LEU A 108 -8. .586 63. .011 28. .606 1. .00 0. .00 xxxx 707

ATOM 708 C LEU A 108 -8. .441 62. .034 29. .762 1. .00 0. .00 xxxx 708

ATOM 709 O LEU A 108 -7. .395 61. .964 30. .406 1. .00 0. .00 xxxx 709

ATOM 710 CB LEU A 108 -7. .845 62. .477 27. .380 1. .00 0. .00 xxxx 710

ATOM 711 CG LEU A 108 -8. .200 63. .120 26. .038 1. .00 0. .00 xxxx 711

ATOM 712 CD1 LEU A 108 -7. .440 62. .440 24. .908 1. .00 0. .00 xxxx 712

ATOM 713 CD2 LEU A 108 -9. .705 63. .067 25. .796 1. .00 0. .00 xxxx 713

ATOM 714 N LEU A 109 -9. .507 61. .284 30. .021 1. .00 0. .00 xxxx 714

ATOM 715 CA LEU A 109 -9. .450 60. .171 30. .953 1. .00 0. .00 xxxx 715

ATOM 716 C LEU A 109 -9. .620 58. .862 30. .200 1. .00 0. .00 xxxx 716

ATOM 717 O LEU A 109 -10. .591 58. .687 29. .462 1. .00 0. .00 xxxx 717

ATOM 718 CB LEU A 109 -10. .530 60. .294 32. .031 1. .00 0. .00 xxxx 718

ATOM 719 CG LEU A 109 -10. .652 59. .069 32. .943 1. .00 0. .00 xxxx 719

ATOM 720 CD1 LEU A 109 -9. .465 58. .982 33. .895 1. .00 0. .00 xxxx 720

ATOM 721 CD2 LEU A 109 -11. .964 59. .072 33. .712 1. .00 0. .00 xxxx 721

ATOM 722 N PHE A 110 -8. .676 57. .947 30. .378 1. .00 0. .00 xxxx 722

ATOM 723 CA PHE A 110 -8. .857 56. .595 29. .874 1. .00 0. .00 xxxx 723

ATOM 724 C PHE A 110 -9. .316 55. .706 31. .024 1. .00 0. .00 xxxx 724

ATOM 725 O PHE A 110 -8. .565 55. .422 31. .957 1. .00 0. .00 xxxx 725

ATOM 726 CB PHE A 110 -7. .575 56. .072 29. .222 1. .00 0. .00 xxxx 726

ATOM 727 CG PHE A 110 -7. .461 56. .424 27. .762 1. .00 0. .00 xxxx 727

ATOM 728 CD1 PHE A 110 -7. .281 57. .739 27. .365 1. .00 0. .00 xxxx 728

ATOM 729 CD2 PHE A 110 -7. .558 55. .444 26. .788 1. .00 0. .00 xxxx 729

ATOM 730 CE1 PHE A 110 -7. .189 58. .069 26. .023 1. .00 0. .00 xxxx 730

ATOM 731 CE2 PHE A 110 -7. .465 55. .767 25. .444 1. .00 0. .00 xxxx 731

ATOM 732 CZ PHE A 110 -7. .279 57. .081 25. .063 1. .00 0. .00 xxxx 732

ATOM 733 N TYR A 111 -10. .573 55. .285 30. .929 1. .00 0. .00 xxxx 733

ATOM 734 CA TYR A 111 -11. .288 54. .600 31. .999 1. .00 0. .00 xxxx 734

ATOM 735 C TYR A 111 -11. .451 53. .115 31. .675 1. .00 0. .00 xxxx 735

ATOM 736 O TYR A 111 -12. .111 52. .760 30. .702 1. .00 0. .00 xxxx 736

ATOM 737 CB TYR A 111 -12. .644 55. .283 32. .196 1. .00 0. .00 xxxx 737

ATOM 738 CG TYR A 111 -13. .602 54. .604 33. .139 1. .00 0. .00 xxxx 738

ATOM 739 CD1 TYR A 111 -14. .751 53. .994 32. .658 1. .00 0. .00 xxxx 739

ATOM 740 CD2 TYR A 111 -13. .372 54. .588 34. .506 1. .00 0. .00 xxxx 740

ATOM 741 CE1 TYR A 111 -15. .640 53. .380 33. .509 1. .00 0. .00 xxxx 741

ATOM 742 CE2 TYR A 111 -14. .259 53. .974 35. .369 1. .00 0. .00 xxxx 742

ATOM 743 CZ TYR A 111 -15. .393 53. .370 34. .861 1. .00 0. .00 xxxx 743

ATOM 744 OH TYR A 111 -16. .286 52. .753 35. .705 1. .00 0. .00 xxxx 744

ATOM 745 N PRO A 112 -10. .838 52. .243 32. .491 1. .00 0. .00 xxxx 745

ATOM 746 CA PRO A 112 -10. .720 50. .820 32. .157 1. .00 0. .00 xxxx 746

ATOM 747 C PRO A 112 -11. .776 49. .881 32. .746 1. .00 0. .00 xxxx 747

ATOM 748 O PRO A 112 -11. .618 48. .670 32. .601 1. .00 0. .00 xxxx 748

ATOM 749 CB PRO A 112 -9. .349 50. .464 32. .732 1. .00 0. .00 xxxx 749

ATOM 750 CG PRO A 112 -9. .266 51. .308 33. .965 1. .00 0. .00 xxxx 750

ATOM 751 CD PRO A 112 -10. .003 52. .599 33. .653 1. .00 0. .00 xxxx 751

ATOM 752 N VAL A 113 -12. .824 50. .397 33. .379 1. .00 0. .00 xxxx 752

ATOM 753 CA VAL A 113 -13. .725 49. .515 34. .122 1. .00 0. .00 xxxx 753

ATOM 754 C VAL A 113 -15. .135 49. .412 33. .538 1. .00 0. .00 xxxx 754

ATOM 755 O VAL A 113 -15. .710 50. .399 33. .081 1. .00 0. .00 xxxx 755

ATOM 756 CB VAL A 113 -13. .846 49. .960 35. .597 1. .00 0. .00 xxxx 756

ATOM 757 CGI VAL A 113 -14. .743 49. .002 36. .370 1. .00 0. .00 xxxx 757

ATOM 758 CG2 VAL A 113 -12. .469 50. .039 36. .243 1. .00 0. .00 xxxx 758

ATOM 759 N GLN A 114 -15. .672 48. .195 33. .548 1. .00 0. .00 xxxx 759

ATOM 760 CA GLN A 114 -17. .074 47. .943 33. .221 1. .00 0. .00 xxxx 760

ATOM 761 C GLN A 114 -17. .998 48. .907 33. .966 1. .00 0. .00 xxxx 761

ATOM 762 O GLN A 114 -17. .713 49. .289 35. .101 1. .00 0. .00 xxxx 762

ATOM 763 CB GLN A 114 -17. .440 46. .493 33. .554 1. .00 0. .00 xxxx 763

ATOM 764 CG GLN A 114 -17. .139 46. .081 34. .996 1. .00 0. .00 xxxx 764

ATOM 765 CD GLN A 114 -18. .215 46. .511 35. .979 1. .00 0. .00 xxxx 765

ATOM 766 OE1 GLN A 114 -17. .920 46. .887 37. .115 1. .00 0. .00 xxxx 766

ATOM 767 NE2 GLN A 114 -19. .469 46. .444 35. .551 1. .00 0. .00 xxxx 767

ATOM 768 N TYR A 115 -19. .101 49. .303 33. .338 1. .00 0. .00 xxxx 768

ATOM 769 CA TYR A 115 -20. .004 50. .247 33. .987 1. .00 0. .00 xxxx 769

ATOM 770 C TYR A 115 -21. .408 50. .254 33. .378 1. .00 0. .00 xxxx 770

ATOM 771 O TYR A 115 -21. .729 49. .447 32. .502 1. .00 0. .00 xxxx 771

ATOM 772 CB TYR A 115 -19. .392 51. .657 33. .960 1. .00 0. .00 xxxx 772 Attorney Docket No. 35327-522001 WO

ATOM 773 CG TYR A 115 -19. .652 52. .454 32. .699 1. .00 0. .00 xxxx 773

ATOM 774 CD1 TYR A 115 -19. .157 52. .037 31. .470 1. .00 0. .00 xxxx 774

ATOM 775 CD2 TYR A 115 -20. .375 53. .638 32. .745 1. .00 0. .00 xxxx 775

ATOM 776 CE1 TYR A 115 -19. .394 52. .770 30. .317 1. .00 0. .00 xxxx 776

ATOM 777 CE2 TYR A 115 -20. .614 54. .377 31. .602 1. .00 0. .00 xxxx 777

ATOM 778 CZ TYR A 115 -20. .125 53. .941 30. .392 1. .00 0. .00 xxxx 778

ATOM 779 OH TYR A 115 -20. .367 54. .684 29. .257 1. .00 0. .00 xxxx 779

ATOM 780 N GLU A 116 -22. .241 51. .170 33. .863 1. .00 0. .00 xxxx 780

ATOM 781 CA GLU A 116 -23. .673 51. .161 33. .576 1. .00 0. .00 xxxx 781

ATOM 782 C GLU A 116 -24. .041 51. .761 32. .221 1. .00 0. .00 xxxx 782

ATOM 783 O GLU A 116 -25. .173 51. .613 31. .762 1. .00 0. .00 xxxx 783

ATOM 784 CB GLU A 116 -24. .424 51. .910 34. .681 1. .00 0. .00 xxxx 784

ATOM 785 CG GLU A 116 -24. .204 53. .420 34. .681 1. .00 0. .00 xxxx 785

ATOM 786 CD GLU A 116 -22. .870 53. .832 35. .282 1. .00 0. .00 xxxx 786

ATOM 787 OE1 GLU A 116 -22. .158 52. .962 35. .831 1. .00 0. .00 xxxx 787

ATOM 788 OE2 GLU A 116 -22. .536 55. .034 35. .214 1. .00 0. .00 xxxx 788

ATOM 789 N GLY A 117 -23. .093 52. .438 31. .584 1. .00 0. .00 xxxx 789

ATOM 790 CA GLY A 117 -23. .380 53. .130 30. .341 1. .00 0. .00 xxxx 790

ATOM 791 C GLY A 117 -24. .174 54. .403 30. .578 1. .00 0. .00 xxxx 791

ATOM 792 O GLY A 117 -23. .981 55. .079 31. .589 1. .00 0. .00 xxxx 792

ATOM 793 N LEU A 118 -25. .069 54. .728 29. .648 1. .00 0. .00 xxxx 793

ATOM 794 CA LEU A 118 -25. .884 55. .937 29. .751 1. .00 0. .00 xxxx 794

ATOM 795 C LEU A 118 -25. .006 57. .178 29. .882 1. .00 0. .00 xxxx 795

ATOM 796 O LEU A 118 -25. .378 58. .155 30. .532 1. .00 0. .00 xxxx 796

ATOM 797 CB LEU A 118 -26. .848 55. .838 30. .934 1. .00 0. .00 xxxx 797

ATOM 798 CG LEU A 118 -27. .837 54. .674 30. .876 1. .00 0. .00 xxxx 798

ATOM 799 CD1 LEU A 118 -28. .815 54. .738 32. .035 1. .00 0. .00 xxxx 799

ATOM 800 CD2 LEU A 118 -28. .578 54. .672 29. .547 1. .00 0. .00 xxxx 800

ATOM 801 N GLU A 119 -23. .837 57. .122 29. .254 1. .00 0. .00 xxxx 801

ATOM 802 CA GLU A 119 -22. .868 58. .207 29. .315 1. .00 0. .00 xxxx 802

ATOM 803 C GLU A 119 -21. .970 58. .175 28. .084 1. .00 0. .00 xxxx 803

ATOM 804 O GLU A 119 -21. .747 57. .115 27. .501 1. .00 0. .00 xxxx 804

ATOM 805 CB GLU A 119 -22. .032 58. .102 30. .592 1. .00 0. .00 xxxx 805

ATOM 806 CG GLU A 119 -21. .065 59. .252 30. .813 1. .00 0. .00 xxxx 806

ATOM 807 CD GLU A 119 -20. .138 59. .005 31. .989 1. .00 0. .00 xxxx 807

ATOM 808 OE1 GLU A 119 -20. .617 59. .049 33. .143 1. .00 0. .00 xxxx 808

ATOM 809 OE2 GLU A 119 -18. .933 58. .761 31. .761 1. .00 0. .00 xxxx 809

ATOM 810 N SER A 120 -21. .465 59. .338 27. .686 1. .00 0. .00 xxxx 810

ATOM 811 CA SER A 120 -20. .501 59. .414 26. .593 1. .00 0. .00 xxxx 811

ATOM 812 C SER A 120 -19. .807 60. .770 26. .561 1. .00 0. .00 xxxx 812

ATOM 813 O SER A 120 -20. .096 61. .607 25. .705 1. .00 0. .00 xxxx 813

ATOM 814 CB SER A 120 -21. .181 59. .142 25. .250 1. .00 0. .00 xxxx 814

ATOM 815 OG SER A 120 -21. .364 57. .751 25. .041 1. .00 0. .00 xxxx 815

ATOM 816 N SER A 121 -18. .890 60. .981 27. .498 1. .00 0. .00 xxxx 816

ATOM 817 CA SER A 121 -18. .124 62. .218 27. .552 1. .00 0. .00 xxxx 817

ATOM 818 C SER A 121 -17. .110 62. .267 26. .417 1. .00 0. .00 xxxx 818

ATOM 819 O SER A 121 -16. .403 61. .292 26. .171 1. .00 0. .00 xxxx 819

ATOM 820 CB SER A 121 -17. .412 62. .353 28. .900 1. .00 0. .00 xxxx 820

ATOM 821 OG SER A 121 -16. .499 63. .439 28. .891 1. .00 0. .00 xxxx 821

ATOM 822 N PRO A 122 -17. .035 63. .409 25. .718 1. .00 0. .00 xxxx 822

ATOM 823 CA PRO A 122 -16. .027 63. .577 24. .667 1. .00 0. .00 xxxx 823

ATOM 824 C PRO A 122 -14. .613 63. .568 25. .239 1. .00 0. .00 xxxx 824

ATOM 825 O PRO A 122 -13. .642 63. .455 24. .491 1. .00 0. .00 xxxx 825

ATOM 826 CB PRO A 122 -16. .371 64. .944 24. .068 1. .00 0. .00 xxxx 826

ATOM 827 CG PRO A 122 -17. .057 65. .672 25. .176 1. .00 0. .00 xxxx 827

ATOM 828 CD PRO A 122 -17. .848 64. .623 25. .905 1. .00 0. .00 xxxx 828

ATOM 829 N ASN A 123 -14. .508 63. .675 26. .561 1. .00 0. .00 xxxx 829

ATOM 830 CA ASN A 123 -13. .212 63. .716 27. .226 1. .00 0. .00 xxxx 830

ATOM 831 C ASN A 123 -12. .903 62. .437 27. .998 1. .00 0. .00 xxxx 831

ATOM 832 O ASN A 123 -12. .010 62. .414 28. .844 1. .00 0. .00 xxxx 832

ATOM 833 CB ASN A 123 -13. .143 64. .923 28. .162 1. .00 0. .00 xxxx 833

ATOM 834 CG ASN A 123 -13. .232 66. .238 27. .416 1. .00 0. .00 xxxx 834

ATOM 835 OD1 ASN A 123 -14. .314 66. .801 27. .254 1. .00 0. .00 xxxx 835

ATOM 836 ND2 ASN A 123 -12. .092 66. .728 26. .944 1. .00 0. .00 xxxx 836

ATOM 837 N ILE A 124 -13. .649 61. .377 27. .708 1. .00 0. .00 xxxx 837

ATOM 838 CA ILE A 124 -13. .376 60. .073 28. .299 1. .00 0. .00 xxxx 838

ATOM 839 C ILE A 124 -13. .328 58. .987 27. .234 1. .00 0. .00 xxxx 839 Attorney Docket No. 35327-522001 WO

ATOM 840 O ILE A 124 -14. .194 58. .921 26. .361 1. .00 0. .00 xxxx 840

ATOM 841 CB ILE A 124 -14. .434 59. .681 29. .351 1. .00 0. .00 xxxx 841

ATOM 842 CGI ILE A 124 -14. .496 60. .717 30. .474 1. .00 0. .00 xxxx 842

ATOM 843 CG2 ILE A 124 -14. .127 58. .303 29. .928 1. .00 0. .00 xxxx 843

ATOM 844 CD1 ILE A 124 -15. .513 60. .382 31. .545 1. .00 0. .00 xxxx 844

ATOM 845 N PHE A 125 -12. .311 58. .137 27. .309 1. .00 0. .00 xxxx 845

ATOM 846 CA PHE A 125 -12. .273 56. .931 26. .496 1. .00 0. .00 xxxx 846

ATOM 847 C PHE A 125 -12. .527 55. .719 27. .387 1. .00 0. .00 xxxx 847

ATOM 848 O PHE A 125 -11. .841 55. .516 28. .390 1. .00 0. .00 xxxx 848

ATOM 849 CB PHE A 125 -10. .936 56. .811 25. .760 1. .00 0. .00 xxxx 849

ATOM 850 CG PHE A 125 -10. .840 57. .687 24. .542 1. .00 0. .00 xxxx 850

ATOM 851 CD1 PHE A 125 -10. .424 59. .003 24. .650 1. .00 0. .00 xxxx 851

ATOM 852 CD2 PHE A 125 -11. .180 57. .197 23. .292 1. .00 0. .00 xxxx 852

ATOM 853 CE1 PHE A 125 -10. .343 59. .814 23. .532 1. .00 0. .00 xxxx 853

ATOM 854 CE2 PHE A 125 -11. .100 58. .002 22. .170 1. .00 0. .00 xxxx 854

ATOM 855 CZ PHE A 125 -10. .679 59. .311 22. .289 1. .00 0. .00 xxxx 855

ATOM 856 N TYR A 126 -13. .517 54. .919 27. .009 1. .00 0. .00 xxxx 856

ATOM 857 CA TYR A 126 -14. .014 53. .844 27. .859 1. .00 0. .00 xxxx 857

ATOM 858 C TYR A 126 -13. .481 52. .493 27. .398 1. .00 0. .00 xxxx 858

ATOM 859 O TYR A 126 -13. .900 51. .973 26. .364 1. .00 0. .00 xxxx 859

ATOM 860 CB TYR A 126 -15. .546 53. .826 27. .857 1. .00 0. .00 xxxx 860

ATOM 861 CG TYR A 126 -16. .194 55. .142 28. .238 1. .00 0. .00 xxxx 861

ATOM 862 CD1 TYR A 126 -16. .226 56. .208 27. .346 1. .00 0. .00 xxxx 862

ATOM 863 CD2 TYR A 126 -16. .791 55. .313 29. .481 1. .00 0. .00 xxxx 863

ATOM 864 CE1 TYR A 126 -16. .824 57. .410 27. .685 1. .00 0. .00 xxxx 864

ATOM 865 CE2 TYR A 126 -17. .393 56. .512 29. .829 1. .00 0. .00 xxxx 865

ATOM 866 CZ TYR A 126 -17. .406 57. .557 28. .927 1. .00 0. .00 xxxx 866

ATOM 867 OH TYR A 126 -18. .003 58. .750 29. .271 1. .00 0. .00 xxxx 867

ATOM 868 N MET A 127 -12. .555 51. .929 28. .167 1. .00 0. .00 xxxx 868

ATOM 869 CA MET A 127 -11. .930 50. .663 27. .806 1. .00 0. .00 xxxx 869

ATOM 870 C MET A 127 -12. .671 49. .480 28. .419 1. .00 0. .00 xxxx 870

ATOM 871 O MET A 127 -12. .481 48. .337 28. .005 1. .00 0. .00 xxxx 871

ATOM 872 CB MET A 127 -10. .464 50. .648 28. .247 1. .00 0. .00 xxxx 872

ATOM 873 CG MET A 127 -9. .625 51. .791 27. .686 1. .00 0. .00 xxxx 873

ATOM 874 SD MET A 127 -9. .443 51. .750 25. .889 1. .00 0. .00 xxxx 874

ATOM 875 CE MET A 127 -10. .621 53. .005 25. .393 1. .00 0. .00 xxxx 875

ATOM 876 N GLY A 128 -13. .514 49. .760 29. .408 1. .00 0. .00 xxxx 876

ATOM 877 CA GLY A 128 -14. .316 48. .729 30. .039 1. .00 0. .00 xxxx 877

ATOM 878 C GLY A 128 -15. .642 48. .537 29. .330 1. .00 0. .00 xxxx 878

ATOM 879 O GLY A 128 -16. .068 49. .390 28. .551 1. .00 0. .00 xxxx 879

ATOM 880 N ALA A 129 -16. .295 47. .413 29. .601 1. .00 0. .00 xxxx 880

ATOM 881 CA ALA A 129 -17. .534 47. .059 28. .919 1. .00 0. .00 xxxx 881

ATOM 882 C ALA A 129 -18. .643 48. .087 29. .123 1. .00 0. .00 xxxx 882

ATOM 883 O ALA A 129 -18. .834 48. .605 30. .224 1. .00 0. .00 xxxx 883

ATOM 884 CB ALA A 129 -18. .010 45. .690 29. .381 1. .00 0. .00 xxxx 884

ATOM 885 N ALA A 130 -19. .367 48. .375 28. .047 1. .00 0. .00 xxxx 885

ATOM 886 CA ALA A 130 -20. .666 49. .022 28. .151 1. .00 0. .00 xxxx 886

ATOM 887 C ALA A 130 -21. .685 47. .949 28. .517 1. .00 0. .00 xxxx 887

ATOM 888 O ALA A 130 -21. .403 46. .758 28. .383 1. .00 0. .00 xxxx 888

ATOM 889 CB ALA A 130 -21. .038 49. .716 26. .851 1. .00 0. .00 xxxx 889

ATOM 890 N PRO A 131 -22. .873 48. .360 28. .983 1. .00 0. .00 xxxx 890

ATOM 891 CA PRO A 131 -23. .846 47. .388 29. .499 1. .00 0. .00 xxxx 891

ATOM 892 C PRO A 131 -24. .266 46. .325 28. .478 1. .00 0. .00 xxxx 892

ATOM 893 O PRO A 131 -24. .526 45. .185 28. .865 1. .00 0. .00 xxxx 893

ATOM 894 CB PRO A 131 -25. .042 48. .266 29. .897 1. .00 0. .00 xxxx 894

ATOM 895 CG PRO A 131 -24. .855 49. .551 29. .145 1. .00 0. .00 xxxx 895

ATOM 896 CD PRO A 131 -23. .377 49. .742 29. .045 1. .00 0. .00 xxxx 896

ATOM 897 N ASN A 132 -24. .316 46. .680 27. .197 1. .00 0. .00 xxxx 897

ATOM 898 CA ASN A 132 -24. .656 45. .700 26. .171 1. .00 0. .00 xxxx 898

ATOM 899 C ASN A 132 -23. .526 44. .689 25. .984 1. .00 0. .00 xxxx 899

ATOM 900 O ASN A 132 -23. .707 43. .649 25. .349 1. .00 0. .00 xxxx 900

ATOM 901 CB ASN A 132 -24. .977 46. .387 24. .841 1. .00 0. .00 xxxx 901

ATOM 902 CG ASN A 132 -23. .746 46. .950 24. .157 1. .00 0. .00 xxxx 902

ATOM 903 OD1 ASN A 132 -22. .991 47. .724 24. .745 1. .00 0. .00 xxxx 903

ATOM 904 ND2 ASN A 132 -23. .537 46. .559 22. .904 1. .00 0. .00 xxxx 904

ATOM 905 N GLN A 133 -22. .365 44. .999 26. .551 1. .00 0. .00 xxxx 905

ATOM 906 CA GLN A 133 -21. .198 44. .131 26. .447 1. .00 0. .00 xxxx 906 Attorney Docket No. 35327-522001 WO

ATOM 907 C GLN A 133 -20. .931 43. .331 27. .722 1. .00 0. .00 xxxx 907

ATOM 908 O GLN A 133 -19. .924 42. .630 27. .815 1. .00 0. .00 xxxx 908

ATOM 909 CB GLN A 133 -19. .958 44. .955 26. .097 1. .00 0. .00 xxxx 909

ATOM 910 CG GLN A 133 -20. .070 45. .739 24. .804 1. .00 0. .00 xxxx 910

ATOM 911 CD GLN A 133 -18. .871 46. .638 24. .572 1. .00 0. .00 xxxx 911

ATOM 912 OE1 GLN A 133 -18. .403 47. .316 25. .487 1. .00 0. .00 xxxx 912

ATOM 913 NE2 GLN A 133 -18. .363 46. .643 23. .344 1. .00 0. .00 xxxx 913

ATOM 914 N GLN A 134 -21. .823 43. .437 28. .703 1. .00 0. .00 xxxx 914

ATOM 915 CA GLN A 134 -21. .654 42. .691 29. .948 1. .00 0. .00 xxxx 915

ATOM 916 C GLN A 134 -22. .981 42. .367 30. .630 1. .00 0. .00 xxxx 916

ATOM 917 O GLN A 134 -23. .469 41. .240 30. .555 1. .00 0. .00 xxxx 917

ATOM 918 CB GLN A 134 -20. .758 43. .464 30. .921 1. .00 0. .00 xxxx 918

ATOM 919 CG GLN A 134 -20. .417 42. .681 32. .185 1. .00 0. .00 xxxx 919

ATOM 920 CD GLN A 134 -19. .788 43. .542 33. .264 1. .00 0. .00 xxxx 920

ATOM 921 OE1 GLN A 134 -20. .234 44. .660 33. .522 1. .00 0. .00 xxxx 921

ATOM 922 NE2 GLN A 134 -18. .750 43. .019 33. .907 1. .00 0. .00 xxxx 922

ATOM 923 N ILE A 135 -23. .556 43. .363 31. .296 1. .00 0. .00 xxxx 923

ATOM 924 CA ILE A 135 -24. .736 43. .153 32. .129 1. .00 0. .00 xxxx 924

ATOM 925 C ILE A 135 -25. .935 42. .612 31. .350 1. .00 0. .00 xxxx 925

ATOM 926 O ILE A 135 -26. .633 41. .717 31. .825 1. .00 0. .00 xxxx 926

ATOM 927 CB ILE A 135 -25. .151 44. .455 32. .838 1. .00 0. .00 xxxx 927

ATOM 928 CGI ILE A 135 -24. .154 44. .793 33. .951 1. .00 0. .00 xxxx 928

ATOM 929 CD1 ILE A 135 -24. .356 46. .165 34. .560 1. .00 0. .00 xxxx 929

ATOM 930 CG2 ILE A 135 -26. .548 44. .324 33. .415 1. .00 0. .00 xxxx 930

ATOM 931 N VAL A 136 -26. .171 43. .149 30. .157 1. .00 0. .00 xxxx 931

ATOM 932 CA VAL A 136 -27. .332 42. .745 29. .368 1. .00 0. .00 xxxx 932

ATOM 933 C VAL A 136 -27. .259 41. .279 28. .934 1. .00 0. .00 xxxx 933

ATOM 934 O VAL A 136 -28. .188 40. .512 29. .184 1. .00 0. .00 xxxx 934

ATOM 935 CB VAL A 136 -27. .503 43. .634 28. .121 1. .00 0. .00 xxxx 935

ATOM 936 CGI VAL A 136 -28. .532 43. .033 27. .178 1. .00 0. .00 xxxx 936

ATOM 937 CG2 VAL A 136 -27. .904 45. .043 28. .529 1. .00 0. .00 xxxx 937

ATOM 938 N PRO A 137 -26. .155 40. .882 28. .280 1. .00 0. .00 xxxx 938

ATOM 939 CA PRO A 137 -25. .986 39. .469 27. .919 1. .00 0. .00 xxxx 939

ATOM 940 C PRO A 137 -25. .941 38. .554 29. .144 1. .00 0. .00 xxxx 940

ATOM 941 O PRO A 137 -26. .349 37. .395 29. .053 1. .00 0. .00 xxxx 941

ATOM 942 CB PRO A 137 -24. .651 39. .451 27. .160 1. .00 0. .00 xxxx 942

ATOM 943 CG PRO A 137 -23. .976 40. .738 27. .506 1. .00 0. .00 xxxx 943

ATOM 944 CD PRO A 137 -25. .075 41. .723 27. .739 1. .00 0. .00 xxxx 944

ATOM 945 N ALA A 138 -25. .456 39. .071 30. .270 1. .00 0. .00 xxxx 945

ATOM 946 CA ALA A 138 -25. .423 38. .308 31. .514 1. .00 0. .00 xxxx 946

ATOM 947 C ALA A 138 -26. .836 37. .914 31. .933 1. .00 0. .00 xxxx 947

ATOM 948 O ALA A 138 -27. .098 36. .755 32. .256 1. .00 0. .00 xxxx 948

ATOM 949 CB ALA A 138 -24. .742 39. .111 32. .618 1. .00 0. .00 xxxx 949

ATOM 950 N VAL A 139 -27. .740 38. .888 31. .928 1. .00 0. .00 xxxx 950

ATOM 951 CA VAL A 139 -29. .134 38. .642 32. .277 1. .00 0. .00 xxxx 951

ATOM 952 C VAL A 139 -29. .783 37. .648 31. .318 1. .00 0. .00 xxxx 952

ATOM 953 O VAL A 139 -30. .472 36. .720 31. .747 1. .00 0. .00 xxxx 953

ATOM 954 CB VAL A 139 -29. .956 39. .946 32. .283 1. .00 0. .00 xxxx 954

ATOM 955 CGI VAL A 139 -31. .439 39. .641 32. .460 1. .00 0. .00 xxxx 955

ATOM 956 CG2 VAL A 139 -29. .457 40. .880 33. .377 1. .00 0. .00 xxxx 956

ATOM 957 N LYS A 140 -29. .565 37. .845 30. .020 1. .00 0. .00 xxxx 957

ATOM 958 CA LYS A 140 -30. .161 36. .974 29. .012 1. .00 0. .00 xxxx 958

ATOM 959 C LYS A 140 -29. .678 35. .533 29. .148 1. .00 0. .00 xxxx 959

ATOM 960 O LYS A 140 -30. .478 34. .601 29. .094 1. .00 0. .00 xxxx 960

ATOM 961 CB LYS A 140 -29. .872 37. .488 27. .599 1. .00 0. .00 xxxx 961

ATOM 962 CG LYS A 140 -30. .590 36. .683 26. .523 1. .00 0. .00 xxxx 962

ATOM 963 CD LYS A 140 -30. .709 37. .447 25. .216 1. .00 0. .00 xxxx 963

ATOM 964 CE LYS A 140 -31. .921 36. .980 24. .418 1. .00 0. .00 xxxx 964

ATOM 965 NZ LYS A 140 -31. .906 35. .511 24. .172 1. .00 0. .00 xxxx 965

ATOM 966 N TRP A 141 -28. .371 35. .353 29. .317 1. .00 0. .00 xxxx 966

ATOM 967 CA TRP A 141 -27. .806 34. .015 29. .458 1. .00 0. .00 xxxx 967

ATOM 968 C TRP A 141 -28. .364 33. .328 30. .699 1. .00 0. .00 xxxx 968

ATOM 969 O TRP A 141 -28. .711 32. .146 30. .665 1. .00 0. .00 xxxx 969

ATOM 970 CB TRP A 141 -26. .279 34. .074 29. .527 1. .00 0. .00 xxxx 970

ATOM 971 CG TRP A 141 -25. .632 32. .726 29. .655 1. .00 0. .00 xxxx 971

ATOM 972 CD1 TRP A 141 -25. .301 31. .875 28. .640 1. .00 0. .00 xxxx 972

ATOM 973 CD2 TRP A 141 -25. .231 32. .076 30. .869 1. .00 0. .00 xxxx 973 Attorney Docket No. 35327-522001 WO

ATOM 974 NE1 TRP A 141 -24. .724 30. .735 29. .145 1. .00 0. .00 xxxx 974

ATOM 975 CE2 TRP A 141 -24. .668 30. .834 30. .511 1. .00 0. .00 xxxx 975

ATOM 976 CE3 TRP A 141 -25. .294 32. .423 32. .222 1. .00 0. .00 xxxx 976

ATOM 977 CZ2 TRP A 141 -24. .171 29. .939 31. .456 1. .00 0. .00 xxxx 977

ATOM 978 CZ3 TRP A 141 -24. .801 31. .532 33. .160 1. .00 0. .00 xxxx 978

ATOM 979 CH2 TRP A 141 -24. .246 30. .305 32. .772 1. .00 0. .00 xxxx 979

ATOM 980 N LEU A 142 -28. .446 34. .079 31. .792 1. .00 0. .00 xxxx 980

ATOM 981 CA LEU A 142 -29. .038 33. .575 33. .024 1. .00 0. .00 xxxx 981

ATOM 982 C LEU A 142 -30. .481 33. .149 32. .788 1. .00 0. .00 xxxx 982

ATOM 983 O LEU A 142 -30. .899 32. .070 33. .210 1. .00 0. .00 xxxx 983

ATOM 984 CB LEU A 142 -28. .969 34. .631 34. .128 1. .00 0. .00 xxxx 984

ATOM 985 CG LEU A 142 -27. .594 34. .845 34. .765 1. .00 0. .00 xxxx 985

ATOM 986 CD1 LEU A 142 -27. .621 36. .018 35. .732 1. .00 0. .00 xxxx 986

ATOM 987 CD2 LEU A 142 -27. .137 33. .582 35. .471 1. .00 0. .00 xxxx 987

ATOM 988 N PHE A 143 -31. .237 34. .005 32. .110 1. .00 0. .00 xxxx 988

ATOM 989 CA PHE A 143 -32. .648 33. .743 31. .853 1. .00 0. .00 xxxx 989

ATOM 990 C PHE A 143 -32. .827 32. .521 30. .956 1. .00 0. .00 xxxx 990

ATOM 991 O PHE A 143 -33. .650 31. .650 31. .237 1. .00 0. .00 xxxx 991

ATOM 992 CB PHE A 143 -33. .311 34. .968 31. .218 1. .00 0. .00 xxxx 992

ATOM 993 CG PHE A 143 -34. .799 34. .837 31. .055 1. .00 0. .00 xxxx 993

ATOM 994 CD1 PHE A 143 -35. .649 35. .067 32. .125 1. .00 0. .00 xxxx 994

ATOM 995 CD2 PHE A 143 -35. .347 34. .482 29. .835 1. .00 0. .00 xxxx 995

ATOM 996 CE1 PHE A 143 -37. .020 34. .949 31. .979 1. .00 0. .00 xxxx 996

ATOM 997 CE2 PHE A 143 -36. .717 34. .360 29. .683 1. .00 0. .00 xxxx 997

ATOM 998 CZ PHE A 143 -37. .553 34. .594 30. .756 1. .00 0. .00 xxxx 998

ATOM 999 N ASP A 144 -32. .045 32. .458 29. .881 1. .00 0. .00 xxxx 999

ATOM 1000 CA ASP A 144 -32. .119 31. .343 28. .941 1. .00 0. .00 XXXX1000

ATOM 1001 C ASP A 144 -31. .658 30. .027 29. .560 1. .00 0. .00 XXXX1001

ATOM 1002 O ASP A 144 -31. .891 28. .956 28. .997 1. .00 0. .00 XXXX1002

ATOM 1003 CB ASP A 144 -31. .292 31. .642 27. .688 1. .00 0. .00 XXXX1003

ATOM 1004 CG ASP A 144 -31. .944 32. .678 26. .799 1. .00 0. .00 XXXX1004

ATOM 1005 OD1 ASP A 144 -33. .101 33. .048 27. .084 1. .00 0. .00 XXXX1005

ATOM 1006 OD2 ASP A 144 -31. .308 33. .117 25. .818 1. .00 0. .00 XXXX1006

ATOM 1007 N ASN A 145 -30. .998 30. .108 30. .710 1. .00 0. .00 XXXX1007

ATOM 1008 CA ASN A 145 -30. .560 28. .907 31. .411 1. .00 0. .00 XXXX1008

ATOM 1009 C ASN A 145 -31. .353 28. .653 32. .693 1. .00 0. .00 XXXX1009

ATOM 1010 O ASN A 145 -30. .859 28. .019 33. .625 1. .00 0. .00 XXXX1010

ATOM 1011 CB ASN A 145 -29. .065 28. .988 31. .717 1. .00 0. .00 XXXX1011

ATOM 1012 CG ASN A 145 -28. .210 28. .738 30. .488 1. .00 0. .00 XXXX1012

ATOM 1013 OD1 ASN A 145 -27. .887 27. .594 30. .165 1. .00 0. .00 XXXX1013

ATOM 1014 ND2 ASN A 145 -27. .843 29. .809 29. .791 1. .00 0. .00 XXXX1014

ATOM 1015 N GLY A 146 -32. .585 29. .151 32. .730 1. .00 0. .00 XXXX1015

ATOM 1016 CA GLY A 146 -33. .528 28. .778 33. .770 1. .00 0. .00 XXXX1016

ATOM 1017 C GLY A 146 -33. .654 29. .689 34. .978 1. .00 0. .00 XXXX1017

ATOM 1018 O GLY A 146 -34. .473 29. .430 35. .860 1. .00 0. .00 XXXX1018

ATOM 1019 N LYS A 147 -32. .859 30. .752 35. .033 1. .00 0. .00 XXXX1019

ATOM 1020 CA LYS A 147 -32. .948 31. .687 36. .151 1. .00 0. .00 XXXX1020

ATOM 1021 C LYS A 147 -33. .997 32. .764 35. .885 1. .00 0. .00 XXXX1021

ATOM 1022 O LYS A 147 -33. .801 33. .639 35. .043 1. .00 0. .00 XXXX1022

ATOM 1023 CB LYS A 147 -31. .588 32. .330 36. .429 1. .00 0. .00 XXXX1023

ATOM 1024 CG LYS A 147 -30. .446 31. .336 36. .534 1. .00 0. .00 XXXX1024

ATOM 1025 CD LYS A 147 -30. .761 30. .239 37. .537 1. .00 0. .00 XXXX1025

ATOM 1026 CE LYS A 147 -29. .720 29. .135 37. .485 1. .00 0. .00 XXXX1026

ATOM 1027 NZ LYS A 147 -30. .003 28. .062 38. .480 1. .00 0. .00 XXXX1027

ATOM 1028 N LYS A 148 -35. .109 32. .695 36. .612 1. .00 0. .00 XXXX1028

ATOM 1029 CA LYS A 148 -36. .242 33. .581 36. .366 1. .00 0. .00 XXXX1029

ATOM 1030 C LYS A 148 -36. .437 34. .585 37. .498 1. .00 0. .00 XXXX1030

ATOM 1031 O LYS A 148 -36. .973 35. .673 37. .287 1. .00 0. .00 XXXX1031

ATOM 1032 CB LYS A 148 -37. .525 32. .767 36. .183 1. .00 0. .00 XXXX1032

ATOM 1033 CG LYS A 148 -37. .399 31. .596 35. .224 1. .00 0. .00 XXXX1033

ATOM 1034 CD LYS A 148 -37. .052 32. .056 33. .820 1. .00 0. .00 XXXX1034

ATOM 1035 CE LYS A 148 -36. .840 30. .869 32. .893 1. .00 0. .00 XXXX1035

ATOM 1036 NZ LYS A 148 -36. .646 31. .303 31. .484 1. .00 0. .00 XXXX1036

ATOM 1037 N ARG A 149 -36. .005 34. .211 38. .698 1. .00 0. .00 XXXX1037

ATOM 1038 CA ARG A 149 -36. .248 35. .020 39. .887 1. .00 0. .00 XXXX1038

ATOM 1039 C ARG A 149 -34. .948 35. .592 40. .441 1. .00 0. .00 XXXX1039

ATOM 1040 O ARG A 149 -34. .189 34. .900 41. .121 1. .00 0. .00 XXXX1040 Attorney Docket No. 35327-522001 WO

ATOM 1041 CB ARG A 149 -36. .970 34. .188 40. .947 1. .00 0. .00 XXXX1041

ATOM 1042 CG ARG A 149 -38. .304 33. .625 40. .464 1. .00 0. .00 XXXX1042

ATOM 1043 CD ARG A 149 -38. .805 32. .500 41. .357 1. .00 0. .00 XXXX1043

ATOM 1044 NE ARG A 149 -38. .904 32. .917 42. .750 1. .00 0. .00 XXXX1044

ATOM 1045 CZ ARG A 149 -38. .052 32. .546 43. .700 1. .00 0. .00 XXXX1045

ATOM 1046 NH1 ARG A 149 -37. .033 31. .746 43. .405 1. .00 0. .00 XXXX1046

ATOM 1047 NH2 ARG A 149 -38. .214 32. .974 44. .944 1. .00 0. .00 XXXX1047

ATOM 1048 N PHE A 150 -34. .708 36. .865 40. .149 1. .00 0. .00 XXXX1048

ATOM 1049 CA PHE A 150 -33. .449 37. .518 40. .488 1. .00 0. .00 XXXX1049

ATOM 1050 C PHE A 150 -33. .486 38. .203 41. .849 1. .00 0. .00 XXXX1050

ATOM 1051 O PHE A 150 -34. .455 38. .881 42. .187 1. .00 0. .00 XXXX1051

ATOM 1052 CB PHE A 150 -33. .087 38. .553 39. .417 1. .00 0. .00 XXXX1052

ATOM 1053 CG PHE A 150 -32. .553 37. .958 38. .144 1. .00 0. .00 XXXX1053

ATOM 1054 CD1 PHE A 150 -33. .159 36. .856 37. .562 1. .00 0. .00 XXXX1054

ATOM 1055 CD2 PHE A 150 -31. .453 38. .518 37. .517 1. .00 0. .00 XXXX1055

ATOM 1056 CE1 PHE A 150 -32. .666 36. .316 36. .388 1. .00 0. .00 XXXX1056

ATOM 1057 CE2 PHE A 150 -30. .957 37. .985 36. .342 1. .00 0. .00 XXXX1057

ATOM 1058 CZ PHE A 150 -31. .565 36. .882 35. .777 1. .00 0. .00 XXXX1058

ATOM 1059 N TYR A 151 -32. .422 38. .024 42. .625 1. .00 0. .00 XXXX1059

ATOM 1060 CA TYR A 151 -32. .211 38. .827 43. .822 1. .00 0. .00 XXXX1060

ATOM 1061 C TYR A 151 -31. .055 39. .787 43. .565 1. .00 0. .00 XXXX1061

ATOM 1062 O TYR A 151 -29. .930 39. .360 43. .303 1. .00 0. .00 XXXX1062

ATOM 1063 CB TYR A 151 -31. .929 37. .949 45. .043 1. .00 0. .00 XXXX1063

ATOM 1064 CG TYR A 151 -32. .159 38. .653 46. .364 1. .00 0. .00 XXXX1064

ATOM 1065 CD1 TYR A 151 -33. .262 38. .348 47. .152 1. .00 0. .00 XXXX1065

ATOM 1066 CD2 TYR A 151 -31. .287 39. .638 46. .812 1. .00 0. .00 XXXX1066

ATOM 1067 CE1 TYR A 151 -33. .482 38. .992 48. .356 1. .00 0. .00 XXXX1067

ATOM 1068 CE2 TYR A 151 -31. .498 40. .288 48. .015 1. .00 0. .00 XXXX1068

ATOM 1069 CZ TYR A 151 -32. .597 39. .961 48. .782 1. .00 0. .00 XXXX1069

ATOM 1070 OH TYR A 151 -32. .812 40. .605 49. .979 1. .00 0. .00 XXXX1070

ATOM 1071 N LEU A 152 -31. .339 41. .083 43. .632 1. .00 0. .00 XXXX1071

ATOM 1072 CA LEU A 152 -30. .340 42. .098 43. .316 1. .00 0. .00 XXXX1072

ATOM 1073 C LEU A 152 -29. .632 42. .616 44. .564 1. .00 0. .00 XXXX1073

ATOM 1074 O LEU A 152 -30. .272 43. .051 45. .521 1. .00 0. .00 XXXX1074

ATOM 1075 CB LEU A 152 -30. .990 43. .258 42. .560 1. .00 0. .00 XXXX1075

ATOM 1076 CG LEU A 152 -31. .824 42. .858 41. .340 1. .00 0. .00 XXXX1076

ATOM 1077 CD1 LEU A 152 -32. .433 44. .085 40. .678 1. .00 0. .00 XXXX1077

ATOM 1078 CD2 LEU A 152 -30. .980 42. .068 40. .349 1. .00 0. .00 XXXX1078

ATOM 1079 N LEU A 153 -28. .305 42. .562 44. .542 1. .00 0. .00 XXXX1079

ATOM 1080 CA LEU A 153 -27. .491 43. .051 45. .646 1. .00 0. .00 XXXX1080

ATOM 1081 C LEU A 153 -26. .286 43. .819 45. .119 1. .00 0. .00 XXXX1081

ATOM 1082 O LEU A 153 -25. .509 43. .294 44. .323 1. .00 0. .00 XXXX1082

ATOM 1083 CB LEU A 153 -27. .030 41. .892 46. .532 1. .00 0. .00 XXXX1083

ATOM 1084 CG LEU A 153 -25. .990 42. .236 47. .603 1. .00 0. .00 XXXX1084

ATOM 1085 CD1 LEU A 153 -26. .593 43. .142 48. .669 1. .00 0. .00 XXXX1085

ATOM 1086 CD2 LEU A 153 -25. .402 40. .976 48. .226 1. .00 0. .00 XXXX1086

ATOM 1087 N GLY A 154 -26. .135 45. .063 45. .559 1. .00 0. .00 XXXX1087

ATOM 1088 CA GLY A 154 -25. .026 45. .889 45. .119 1. .00 0. .00 XXXX1088

ATOM 1089 C GLY A 154 -24. .634 46. .961 46. .115 1. .00 0. .00 XXXX1089

ATOM 1090 O GLY A 154 -25. .306 47. .164 47. .127 1. .00 0. .00 XXXX1090

ATOM 1091 N SER A 155 -23. .535 47. .651 45. .827 1. .00 0. .00 XXXX1091

ATOM 1092 CA SER A 155 -23. .095 48. .766 46. .655 1. .00 0. .00 XXXX1092

ATOM 1093 C SER A 155 -23. .945 49. .996 46. .364 1. .00 0. .00 XXXX1093

ATOM 1094 O SER A 155 -24. .453 50. .158 45. .256 1. .00 0. .00 XXXX1094

ATOM 1095 CB SER A 155 -21. .615 49. .064 46. .418 1. .00 0. .00 XXXX1095

ATOM 1096 OG SER A 155 -20. .822 47. .923 46. .705 1. .00 0. .00 XXXX1096

ATOM 1097 N ASP A 156 -24. .101 50. .859 47. .362 1. .00 0. .00 XXXX1097

ATOM 1098 CA ASP A 156 -25. .017 51. .989 47. .249 1. .00 0. .00 XXXX1098

ATOM 1099 C ASP A 156 -24. .390 53. .203 46. .564 1. .00 0. .00 XXXX1099

ATOM 1100 O ASP A 156 -23. .934 54. .133 47. .228 1. .00 0. .00 XXXX1100

ATOM 1101 CB ASP A 156 -25. .535 52. .390 48. .632 1. .00 0. .00 XXXX1101

ATOM 1102 CG ASP A 156 -26. .815 53. .199 48. .560 1. .00 0. .00 XXXX1102

ATOM 1103 OD1 ASP A 156 -27. .198 53. .611 47. .445 1. .00 0. .00 XXXX1103

ATOM 1104 OD2 ASP A 156 -27. .443 53. .419 49. .617 1. .00 0. .00 XXXX1104

ATOM 1105 N TYR A 157 -24. .372 53. .185 45. .235 1. .00 0. .00 XXXX1105

ATOM 1106 CA TYR A 157 -23. .993 54. .357 44. .453 1. .00 0. .00 XXXX1106

ATOM 1107 C TYR A 157 -24. .489 54. .182 43. .019 1. .00 0. .00 XXXX1107 Attorney Docket No. 35327-522001 WO

ATOM 1108 O TYR A 157 -25. .240 53. .251 42. .731 1. .00 0. .00 XXXX1108

ATOM 1109 CB TYR A 157 -22. .478 54. .602 44. .505 1. .00 0. .00 XXXX1109

ATOM 1110 CG TYR A 157 -21. .622 53. .583 43. .791 1. .00 0. .00 XXXX1110

ATOM 1111 CD1 TYR A 157 -21. .055 53. .870 42. .555 1. .00 0. .00 XXXX1111

ATOM 1112 CD2 TYR A 157 -21. .356 52. .344 44. .362 1. .00 0. .00 XXXX1112

ATOM 1113 CE1 TYR A 157 -20. .262 52. .948 41. .899 1. .00 0. .00 XXXX1113

ATOM 1114 CE2 TYR A 157 -20. .564 51. .413 43. .711 1. .00 0. .00 XXXX1114

ATOM 1115 CZ TYR A 157 -20. .019 51. .723 42. .480 1. .00 0. .00 XXXX1115

ATOM 1116 OH TYR A 157 -19. .231 50. .803 41. .827 1. .00 0. .00 XXXX1116

ATOM 1117 N VAL A 158 -24. .074 55. .069 42. .121 1. .00 0. .00 XXXX1117

ATOM 1118 CA VAL A 158 -24. .753 55. .206 40. .835 1. .00 0. .00 XXXX1118

ATOM 1119 C VAL A 158 -24. .658 53. .985 39. .914 1. .00 0. .00 XXXX1119

ATOM 1120 O VAL A 158 -25. .600 53. .704 39. .172 1. .00 0. .00 XXXX1120

ATOM 1121 CB VAL A 158 -24. .229 56. .433 40. .061 1. .00 0. .00 XXXX1121

ATOM 1122 CGI VAL A 158 -22. .766 56. .250 39. .685 1. .00 0. .00 XXXX1122

ATOM 1123 CG2 VAL A 158 -25. .080 56. .680 38. .823 1. .00 0. .00 XXXX1123

ATOM 1124 N PHE A 159 -23. .546 53. .255 39. .950 1. .00 0. .00 XXXX1124

ATOM 1125 CA PHE A 159 -23. .413 52. .113 39. .046 1. .00 0. .00 XXXX1125

ATOM 1126 C PHE A 159 -24. .408 50. .997 39. .356 1. .00 0. .00 XXXX1126

ATOM 1127 O PHE A 159 -25. .187 50. .606 38. .488 1. .00 0. .00 XXXX1127

ATOM 1128 CB PHE A 159 -22. .000 51. .527 39. .067 1. .00 0. .00 XXXX1128

ATOM 1129 CG PHE A 159 -21. .938 50. .132 38. .506 1. .00 0. .00 XXXX1129

ATOM 1130 CD1 PHE A 159 -22. .242 49. .897 37. .174 1. .00 0. .00 XXXX1130

ATOM 1131 CD2 PHE A 159 -21. .615 49. .055 39. .315 1. .00 0. .00 XXXX1131

ATOM 1132 CE1 PHE A 159 -22. .208 48. .617 36. .654 1. .00 0. .00 XXXX1132

ATOM 1133 CE2 PHE A 159 -21. .578 47. .771 38. .800 1. .00 0. .00 XXXX1133

ATOM 1134 CZ PHE A 159 -21. .876 47. .552 37. .468 1. .00 0. .00 XXXX1134

ATOM 1135 N PRO A 160 -24. .383 50. .473 40. .593 1. .00 0. .00 XXXX1135

ATOM 1136 CA PRO A 160 -25. .294 49. .377 40. .934 1. .00 0. .00 XXXX1136

ATOM 1137 C PRO A 160 -26. .766 49. .766 40. .808 1. .00 0. .00 XXXX1137

ATOM 1138 O PRO A 160 -27. .576 48. .945 40. .379 1. .00 0. .00 XXXX1138

ATOM 1139 CB PRO A 160 -24. .933 49. .070 42. .390 1. .00 0. .00 XXXX1139

ATOM 1140 CG PRO A 160 -23. .503 49. .495 42. .508 1. .00 0. .00 XXXX1140

ATOM 1141 CD PRO A 160 -23. .422 50. .742 41. .677 1. .00 0. .00 XXXX1141

ATOM 1142 N ARG A 161 -27. .107 50. .999 41. .169 1. .00 0. .00 XXXX1142

ATOM 1143 CA ARG A 161 -28. .489 51. .458 41. .053 1. .00 0. .00 XXXX1143

ATOM 1144 C ARG A 161 -28. .929 51. .547 39. .591 1. .00 0. .00 XXXX1144

ATOM 1145 O ARG A 161 -30. .036 51. .133 39. .244 1. .00 0. .00 XXXX1145

ATOM 1146 CB ARG A 161 -28. .673 52. .803 41. .759 1. .00 0. .00 XXXX1146

ATOM 1147 CG ARG A 161 -28. .525 52. .704 43. .271 1. .00 0. .00 XXXX1147

ATOM 1148 CD ARG A 161 -29. .255 53. .824 43. .995 1. .00 0. .00 XXXX1148

ATOM 1149 NE ARG A 161 -29. .287 53. .606 45. .440 1. .00 0. .00 XXXX1149

ATOM 1150 CZ ARG A 161 -30. .300 53. .041 46. .092 1. .00 0. .00 XXXX1150

ATOM 1151 NH1 ARG A 161 -31. .377 52. .637 45. .432 1. .00 0. .00 XXXX1151

ATOM 1152 NH2 ARG A 161 -30. .238 52. .884 47. .407 1. .00 0. .00 XXXX1152

ATOM 1153 N THR A 162 -28. .065 52. .088 38. .738 1. .00 0. .00 XXXX1153

ATOM 1154 CA THR A 162 -28. .381 52. .206 37. .318 1. .00 0. .00 XXXX1154

ATOM 1155 C THR A 162 -28. .354 50. .834 36. .658 1. .00 0. .00 XXXX1155

ATOM 1156 O THR A 162 -29. .189 50. .529 35. .806 1. .00 0. .00 XXXX1156

ATOM 1157 CB THR A 162 -27. .404 53. .140 36. .583 1. .00 0. .00 XXXX1157

ATOM 1158 OG1 THR A 162 -27. .400 54. .427 37. .214 1. .00 0. .00 XXXX1158

ATOM 1159 CG2 THR A 162 -27. .822 53. .301 35. .130 1. .00 0. .00 XXXX1159

ATOM 1160 N ALA A 163 -27. .384 50. .015 37. .053 1. .00 0. .00 XXXX1160

ATOM 1161 CA ALA A 163 -27. .275 48. .651 36. .550 1. .00 0. .00 XXXX1161

ATOM 1162 C ALA A 163 -28. .552 47. .867 36. .831 1. .00 0. .00 XXXX1162

ATOM 1163 O ALA A 163 -29. .070 47. .173 35. .958 1. .00 0. .00 XXXX1163

ATOM 1164 CB ALA A 163 -26. .075 47. .951 37. .167 1. .00 0. .00 XXXX1164

ATOM 1165 N ASN A 164 -29. .052 47. .979 38. .058 1. .00 0. .00 XXXX1165

ATOM 1166 CA ASN A 164 -30. .260 47. .265 38. .455 1. .00 0. .00 XXXX1166

ATOM 1167 C ASN A 164 -31. .510 47. .822 37. .783 1. .00 0. .00 XXXX1167

ATOM 1168 O ASN A 164 -32. .461 47. .084 37. .523 1. .00 0. .00 XXXX1168

ATOM 1169 CB ASN A 164 -30. .425 47. .298 39. .976 1. .00 0. .00 XXXX1169

ATOM 1170 CG ASN A 164 -29. .421 46. .412 40. .689 1. .00 0. .00 XXXX1170

ATOM 1171 OD1 ASN A 164 -28. .889 45. .465 40. .108 1. .00 0. .00 XXXX1171

ATOM 1172 ND2 ASN A 164 -29. .161 46. .712 41. .956 1. .00 0. .00 XXXX1172

ATOM 1173 N LYS A 165 -31. .510 49. .123 37. .510 1. .00 0. .00 XXXX1173

ATOM 1174 CA LYS A 165 -32. .591 49. .731 36. .745 1. .00 0. .00 XXXX1174 Attorney Docket No. 35327-522001 WO

ATOM 1175 C LYS A 165 -32. .645 49. .117 35. .349 1. .00 0. .00 XXXX1175

ATOM 1176 O LYS A 165 -33. .721 48. .836 34. .822 1. .00 0. .00 XXXX1176

ATOM 1177 CB LYS A 165 -32. .417 51. .249 36. .656 1. .00 0. .00 XXXX1177

ATOM 1178 CG LYS A 165 -33. .538 51. .953 35. .903 1. .00 0. .00 XXXX1178

ATOM 1179 CD LYS A 165 -33. .278 53. .446 35. .773 1. .00 0. .00 XXXX1179

ATOM 1180 CE LYS A 165 -34. .408 54. .139 35. .023 1. .00 0. .00 XXXX1180

ATOM 1181 NZ LYS A 165 -34. .229 55. .617 34. .977 1. .00 0. .00 XXXX1181

ATOM 1182 N ILE A 166 -31. .471 48. .909 34. .760 1. .00 0. .00 XXXX1182

ATOM 1183 CA ILE A 166 -31. .367 48. .263 33. .458 1. .00 0. .00 XXXX1183

ATOM 1184 C ILE A 166 -31. .808 46. .804 33. .536 1. .00 0. .00 XXXX1184

ATOM 1185 O ILE A 166 -32. .578 46. .331 32. .701 1. .00 0. .00 XXXX1185

ATOM 1186 CB ILE A 166 -29. .929 48. .327 32. .908 1. .00 0. .00 XXXX1186

ATOM 1187 CGI ILE A 166 -29. .534 49. .776 32. .613 1. .00 0. .00 XXXX1187

ATOM 1188 CG2 ILE A 166 -29. .797 47. .468 31. .659 1. .00 0. .00 XXXX1188

ATOM 1189 CD1 ILE A 166 -28. .062 49. .955 32. .308 1. .00 0. .00 XXXX1189

ATOM 1190 N ILE A 167 -31. .311 46. .098 34. .547 1. .00 0. .00 XXXX1190

ATOM 1191 CA ILE A 167 -31. .627 44. .686 34. .730 1. .00 0. .00 XXXX1191

ATOM 1192 C ILE A 167 -33. .129 44. .457 34. .890 1. .00 0. .00 XXXX1192

ATOM 1193 O ILE A 167 -33. .686 43. .520 34. .319 1. .00 0. .00 XXXX1193

ATOM 1194 CB ILE A 167 -30. .893 44. .102 35. .951 1. .00 0. .00 XXXX1194

ATOM 1195 CGI ILE A 167 -29. .378 44. .124 35. .722 1. .00 0. .00 XXXX1195

ATOM 1196 CG2 ILE A 167 -31. .364 42. .685 36. .226 1. .00 0. .00 XXXX1196

ATOM 1197 CD1 ILE A 167 -28. .573 43. .673 36. .923 1. .00 0. .00 XXXX1197

ATOM 1198 N LYS A 168 -33. .781 45. .315 35. .668 1. .00 0. .00 XXXX1198

ATOM 1199 CA LYS A 168 -35. .219 45. .192 35. .890 1. .00 0. .00 XXXX1199

ATOM 1200 C LYS A 168 -36. .009 45. .426 34. .604 1. .00 0. .00 XXXX1200

ATOM 1201 O LYS A 168 -37. .017 44. .763 34. .357 1. .00 0. .00 XXXX1201

ATOM 1202 CB LYS A 168 -35. .681 46. .162 36. .981 1. .00 0. .00 XXXX1202

ATOM 1203 CG LYS A 168 -35. .259 45. .749 38. .383 1. .00 0. .00 XXXX1203

ATOM 1204 CD LYS A 168 -35. .986 46. .548 39. .454 1. .00 0. .00 XXXX1204

ATOM 1205 CE LYS A 168 -35. .275 47. .855 39. .752 1. .00 0. .00 XXXX1205

ATOM 1206 NZ LYS A 168 -35. .812 48. .506 40. .979 1. .00 0. .00 XXXX1206

ATOM 1207 N ALA A 169 -35. .555 46. .375 33. .792 1. .00 0. .00 XXXX1207

ATOM 1208 CA ALA A 169 -36. .215 46. .671 32. .527 1. .00 0. .00 XXXX1208

ATOM 1209 C ALA A 169 -36. .105 45. .490 31. .568 1. .00 0. .00 XXXX1209

ATOM 1210 O ALA A 169 -37. .058 45. .158 30. .862 1. .00 0. .00 XXXX1210

ATOM 1211 CB ALA A 169 -35. .624 47. .924 31. .899 1. .00 0. .00 XXXX1211

ATOM 1212 N TYR A 170 -34. .935 44. .858 31. .552 1. .00 0. .00 XXXX1212

ATOM 1213 CA TYR A 170 -34. .683 43. .725 30. .670 1. .00 0. .00 XXXX1213

ATOM 1214 C TYR A 170 -35. .464 42. .495 31. .124 1. .00 0. .00 XXXX1214

ATOM 1215 O TYR A 170 -36. .057 41. .789 30. .307 1. .00 0. .00 XXXX1215

ATOM 1216 CB TYR A 170 -33. .185 43. .414 30. .616 1. .00 0. .00 XXXX1216

ATOM 1217 CG TYR A 170 -32. .768 42. .565 29. .433 1. .00 0. .00 XXXX1217

ATOM 1218 CD1 TYR A 170 -33. .630 42. .349 28. .365 1. .00 0. .00 XXXX1218

ATOM 1219 CD2 TYR A 170 -31. .506 41. .989 29. .381 1. .00 0. .00 XXXX1219

ATOM 1220 CE1 TYR A 170 -33. .249 41. .576 27. .281 1. .00 0. .00 XXXX1220

ATOM 1221 CE2 TYR A 170 -31. .115 41. .215 28. .303 1. .00 0. .00 XXXX1221

ATOM 1222 CZ TYR A 170 -31. .988 41. .013 27. .256 1. .00 0. .00 XXXX1222

ATOM 1223 OH TYR A 170 -31. .597 40. .245 26. .184 1. .00 0. .00 XXXX1223

ATOM 1224 N LEU A 171 -35. .456 42. .242 32. .430 1. .00 0. .00 XXXX1224

ATOM 1225 CA LEU A 171 -36. .195 41. .119 32. .998 1. .00 0. .00 XXXX1225

ATOM 1226 C LEU A 171 -37. .689 41. .218 32. .712 1. .00 0. .00 XXXX1226

ATOM 1227 O LEU A 171 -38. .337 40. .215 32. .414 1. .00 0. .00 XXXX1227

ATOM 1228 CB LEU A 171 -35. .959 41. .030 34. .508 1. .00 0. .00 XXXX1228

ATOM 1229 CG LEU A 171 -34. .695 40. .285 34. .936 1. .00 0. .00 XXXX1229

ATOM 1230 CD1 LEU A 171 -34. .537 40. .317 36. .451 1. .00 0. .00 XXXX1230

ATOM 1231 CD2 LEU A 171 -34. .729 38. .852 34. .421 1. .00 0. .00 XXXX1231

ATOM 1232 N LYS A 172 -38. .233 42. .426 32. .809 1. .00 0. .00 XXXX1232

ATOM 1233 CA LYS A 172 -39. .637 42. .650 32. .482 1. .00 0. .00 XXXX1233

ATOM 1234 C LYS A 172 -39. .890 42. .298 31. .021 1. .00 0. .00 XXXX1234

ATOM 1235 O LYS A 172 -40. .915 41. .708 30. .676 1. .00 0. .00 XXXX1235

ATOM 1236 CB LYS A 172 -40. .039 44. .100 32. .759 1. .00 0. .00 XXXX1236

ATOM 1237 CG LYS A 172 -41. .459 44. .442 32. .329 1. .00 0. .00 XXXX1237

ATOM 1238 CD LYS A 172 -41. .829 45. .868 32. .704 1. .00 0. .00 XXXX1238

ATOM 1239 CE LYS A 172 -43. .289 46. .164 32. .391 1. .00 0. .00 XXXX1239

ATOM 1240 NZ LYS A 172 -43. .607 45. .977 30. .947 1. .00 0. .00 XXXX1240

ATOM 1241 N TYR A 173 -38. .942 42. .666 30. .167 1. .00 0. .00 XXXX1241 Attorney Docket No. 35327-522001 WO

ATOM 1242 CA TYR A 173 -39. .034 42. .386 28. .742 1. .00 0. .00 XXXX1242

ATOM 1243 C TYR A 173 -38. .992 40. .885 28. .470 1. .00 0. .00 XXXX1243

ATOM 1244 O TYR A 173 -39. .712 40. .382 27. .608 1. .00 0. .00 XXXX1244

ATOM 1245 CB TYR A 173 -37. .906 43. .091 27. .989 1. .00 0. .00 XXXX1245

ATOM 1246 CG TYR A 173 -37. .871 42. .799 26. .507 1. .00 0. .00 XXXX1246

ATOM 1247 CD1 TYR A 173 -38. .734 43. .446 25. .632 1. .00 0. .00 XXXX1247

ATOM 1248 CD2 TYR A 173 -36. .972 41. .880 25. .982 1. .00 0. .00 XXXX1248

ATOM 1249 CE1 TYR A 173 -38. .704 43. .186 24. .277 1. .00 0. .00 XXXX1249

ATOM 1250 CE2 TYR A 173 -36. .936 41. .612 24. .626 1. .00 0. .00 XXXX1250

ATOM 1251 CZ TYR A 173 -37. .804 42. .269 23. .779 1. .00 0. .00 XXXX1251

ATOM 1252 OH TYR A 173 -37. .772 42. .009 22. .429 1. .00 0. .00 XXXX1252

ATOM 1253 N LEU A 174 -38. .147 40. .175 29. .212 1. .00 0. .00 XXXX1253

ATOM 1254 CA LEU A 174 -37. .934 38. .747 28. .986 1. .00 0. .00 XXXX1254

ATOM 1255 C LEU A 174 -39. .021 37. .886 29. .621 1. .00 0. .00 XXXX1255

ATOM 1256 O LEU A 174 -39. .348 36. .813 29. .113 1. .00 0. .00 XXXX1256

ATOM 1257 CB LEU A 174 -36. .564 38. .322 29. .521 1. .00 0. .00 XXXX1257

ATOM 1258 CG LEU A 174 -35. .344 38. .879 28. .784 1. .00 0. .00 XXXX1258

ATOM 1259 CD1 LEU A 174 -34. .069 38. .615 29. .575 1. .00 0. .00 XXXX1259

ATOM 1260 CD2 LEU A 174 -35. .246 38. .285 27. .387 1. .00 0. .00 XXXX1260

ATOM 1261 N GLY A 175 -39. .574 38. .355 30. .734 1. .00 0. .00 XXXX1261

ATOM 1262 CA GLY A 175 -40. .586 37. .602 31. .451 1. .00 0. .00 XXXX1262

ATOM 1263 C GLY A 175 -40. .095 37. .078 32. .788 1. .00 0. .00 XXXX1263

ATOM 1264 O GLY A 175 -40. .703 36. .182 33. .374 1. .00 0. .00 XXXX1264

ATOM 1265 N GLY A 176 -38. .988 37. .636 33. .268 1. .00 0. .00 XXXX1265

ATOM 1266 CA GLY A 176 -38. .481 37. .303 34. .586 1. .00 0. .00 XXXX1266

ATOM 1267 C GLY A 176 -38. .893 38. .361 35. .588 1. .00 0. .00 XXXX1267

ATOM 1268 O GLY A 176 -39. .468 39. .383 35. .213 1. .00 0. .00 XXXX1268

ATOM 1269 N VAL A 177 -38. .602 38. .125 36. .863 1. .00 0. .00 XXXX1269

ATOM 1270 CA VAL A 177 -38. .957 39. .085 37. .902 1. .00 0. .00 XXXX1270

ATOM 1271 C VAL A 177 -37. .850 39. .249 38. .936 1. .00 0. .00 XXXX1271

ATOM 1272 O VAL A 177 -36. .976 38. .393 39. .075 1. .00 0. .00 XXXX1272

ATOM 1273 CB VAL A 177 -40. .251 38. .678 38. .630 1. .00 0. .00 XXXX1273

ATOM 1274 CGI VAL A 177 -41. .443 38. .752 37. .683 1. .00 0. .00 XXXX1274

ATOM 1275 CG2 VAL A 177 -40. .110 37. .283 39. .221 1. .00 0. .00 XXXX1275

ATOM 1276 N VAL A 178 -37. .900 40. .360 39. .661 1. .00 0. .00 XXXX1276

ATOM 1277 CA VAL A 178 -36. .999 40. .592 40. .780 1. .00 0. .00 XXXX1277

ATOM 1278 C VAL A 178 -37. .742 40. .296 42. .075 1. .00 0. .00 XXXX1278

ATOM 1279 O VAL A 178 -38. .820 40. .839 42. .315 1. .00 0. .00 XXXX1279

ATOM 1280 CB VAL A 178 -36. .470 42. .036 40. .797 1. .00 0. .00 XXXX1280

ATOM 1281 CGI VAL A 178 -35. .695 42. .307 42. .080 1. .00 0. .00 XXXX1281

ATOM 1282 CG2 VAL A 178 -35. .600 42. .295 39. .577 1. .00 0. .00 XXXX1282

ATOM 1283 N VAL A 179 -37. .169 39. .431 42. .906 1. .00 0. .00 XXXX1283

ATOM 1284 CA VAL A 179 -37. .821 39. .022 44. .144 1. .00 0. .00 XXXX1284

ATOM 1285 C VAL A 179 -37. .128 39. .628 45. .358 1. .00 0. .00 XXXX1285

ATOM 1286 O VAL A 179 -37. .495 39. .350 46. .500 1. .00 0. .00 XXXX1286

ATOM 1287 CB VAL A 179 -37. .844 37. .489 44. .287 1. .00 0. .00 XXXX1287

ATOM 1288 CGI VAL A 179 -38. .704 36. .867 43. .194 1. .00 0. .00 XXXX1288

ATOM 1289 CG2 VAL A 179 -36. .426 36. .931 44. .246 1. .00 0. .00 XXXX1289

ATOM 1290 N GLY A 180 -36. .124 40. .460 45. .104 1. .00 0. .00 XXXX1290

ATOM 1291 CA GLY A 180 -35. .418 41. .148 46. .166 1. .00 0. .00 XXXX1291

ATOM 1292 C GLY A 180 -34. .399 42. .124 45. .617 1. .00 0. .00 XXXX1292

ATOM 1293 O GLY A 180 -33. .818 41. .898 44. .557 1. .00 0. .00 XXXX1293

ATOM 1294 N GLU A 181 -34. .177 43. .211 46. .346 1. .00 0. .00 XXXX1294

ATOM 1295 CA GLU A 181 -33. .239 44. .242 45. .920 1. .00 0. .00 XXXX1295

ATOM 1296 C GLU A 181 -32. .711 45. .006 47. .126 1. .00 0. .00 XXXX1296

ATOM 1297 O GLU A 181 -33. .470 45. .666 47. .831 1. .00 0. .00 XXXX1297

ATOM 1298 CB GLU A 181 -33. .905 45. .200 44. .929 1. .00 0. .00 XXXX1298

ATOM 1299 CG GLU A 181 -33. .012 46. .340 44. .463 1. .00 0. .00 XXXX1299

ATOM 1300 CD GLU A 181 -33. .714 47. .264 43. .487 1. .00 0. .00 XXXX1300

ATOM 1301 OE1 GLU A 181 -34. .924 47. .068 43. .251 1. .00 0. .00 XXXX1301

ATOM 1302 OE2 GLU A 181 -33. .057 48. .183 42. .954 1. .00 0. .00 XXXX1302

ATOM 1303 N GLU A 182 -31. .405 44. .918 47. .356 1. .00 0. .00 XXXX1303

ATOM 1304 CA GLU A 182 -30. .799 45. .550 48. .520 1. .00 0. .00 XXXX1304

ATOM 1305 C GLU A 182 -29. .478 46. .221 48. .170 1. .00 0. .00 XXXX1305

ATOM 1306 O GLU A 182 -28. .727 45. .729 47. .328 1. .00 0. .00 XXXX1306

ATOM 1307 CB GLU A 182 -30. .579 44. .523 49. .633 1. .00 0. .00 XXXX1307

ATOM 1308 CG GLU A 182 -31. .856 43. .886 50. .153 1. .00 0. .00 XXXX1308 Attorney Docket No. 35327-522001 WO

ATOM 1309 CD GLU A 182 -32. .691 44. .847 50. .974 1. .00 0. .00 XXXX1309

ATOM 1310 OE1 GLU A 182 -32. .103 45. .688 51. .686 1. .00 0. .00 XXXX1310

ATOM 1311 OE2 GLU A 182 -33. .937 44. .760 50. .910 1. .00 0. .00 XXXX1311

ATOM 1312 N TYR A 183 -29. .204 47. .347 48. .820 1. .00 0. .00 XXXX1312

ATOM 1313 CA TYR A 183 -27. .940 48. .048 48. .639 1. .00 0. .00 XXXX1313

ATOM 1314 C TYR A 183 -27. .223 48. .239 49. .968 1. .00 0. .00 XXXX1314

ATOM 1315 O TYR A 183 -27. .851 48. .493 50. .996 1. .00 0. .00 XXXX1315

ATOM 1316 CB TYR A 183 -28. .165 49. .405 47. .969 1. .00 0. .00 XXXX1316

ATOM 1317 CG TYR A 183 -28. .814 49. .307 46. .610 1. .00 0. .00 XXXX1317

ATOM 1318 CD1 TYR A 183 -30. .195 49. .357 46. .473 1. .00 0. .00 XXXX1318

ATOM 1319 CD2 TYR A 183 -28. .047 49. .154 45. .462 1. .00 0. .00 XXXX1319

ATOM 1320 CE1 TYR A 183 -30. .793 49. .260 45. .232 1. .00 0. .00 XXXX1320

ATOM 1321 CE2 TYR A 183 -28. .637 49. .057 44. .217 1. .00 0. .00 XXXX1321

ATOM 1322 CZ TYR A 183 -30. .009 49. .112 44. .108 1. .00 0. .00 XXXX1322

ATOM 1323 OH TYR A 183 -30. .599 49. .015 42. .869 1. .00 0. .00 XXXX1323

ATOM 1324 N THR A 184 -25. .903 48. .115 49. .940 1. .00 0. .00 XXXX1324

ATOM 1325 CA THR A 184 -25. .085 48. .409 51. .104 1. .00 0. .00 XXXX1325

ATOM 1326 C THR A 184 -24. .048 49. .459 50. .737 1. .00 0. .00 XXXX1326

ATOM 1327 O THR A 184 -23. .561 49. .480 49. .606 1. .00 0. .00 XXXX1327

ATOM 1328 CB THR A 184 -24. .380 47. .148 51. .641 1. .00 0. .00 XXXX1328

ATOM 1329 OG1 THR A 184 -23. .593 46. .559 50. .598 1. .00 0. .00 XXXX1329

ATOM 1330 CG2 THR A 184 -25. .400 46. .131 52. .130 1. .00 0. .00 XXXX1330

ATOM 1331 N PRO A 185 -23. .719 50. .346 51. .686 1. .00 0. .00 XXXX1331

ATOM 1332 CA PRO A 185 -22. .670 51. .344 51. .460 1. .00 0. .00 XXXX1332

ATOM 1333 C PRO A 185 -21. .361 50. .672 51. .063 1. .00 0. .00 XXXX1333

ATOM 1334 O PRO A 185 -21. .093 49. .562 51. .524 1. .00 0. .00 XXXX1334

ATOM 1335 CB PRO A 185 -22. .544 52. .039 52. .820 1. .00 0. .00 XXXX1335

ATOM 1336 CG PRO A 185 -23. .873 51. .833 53. .469 1. .00 0. .00 XXXX1336

ATOM 1337 CD PRO A 185 -24. .328 50. .476 53. .021 1. .00 0. .00 XXXX1337

ATOM 1338 N LEU A 186 -20. .583 51. .311 50. .195 1. .00 0. .00 XXXX1338

ATOM 1339 CA LEU A 186 -19. .249 50. .817 49. .878 1. .00 0. .00 XXXX1339

ATOM 1340 C LEU A 186 -18. .465 50. .590 51. .166 1. .00 0. .00 XXXX1340

ATOM 1341 O LEU A 186 -18. .440 51. .452 52. .042 1. .00 0. .00 XXXX1341

ATOM 1342 CB LEU A 186 -18. .508 51. .795 48. .964 1. .00 0. .00 XXXX1342

ATOM 1343 CG LEU A 186 -18. .821 51. .705 47. .469 1. .00 0. .00 XXXX1343

ATOM 1344 CD1 LEU A 186 -18. .272 52. .919 46. .738 1. .00 0. .00 XXXX1344

ATOM 1345 CD2 LEU A 186 -18. .260 50. .421 46. .876 1. .00 0. .00 XXXX1345

ATOM 1346 N GLY A 187 -17. .831 49. .427 51. .278 1. .00 0. .00 XXXX1346

ATOM 1347 CA GLY A 187 -17. .035 49. .111 52. .448 1. .00 0. .00 XXXX1347

ATOM 1348 C GLY A 187 -17. .803 48. .394 53. .544 1. .00 0. .00 XXXX1348

ATOM 1349 O GLY A 187 -17. .214 47. .970 54. .540 1. .00 0. .00 XXXX1349

ATOM 1350 N HIS A 188 -19. .115 48. .261 53. .366 1. .00 0. .00 XXXX1350

ATOM 1351 CA HIS A 188 -19. .958 47. .517 54. .303 1. .00 0. .00 XXXX1351

ATOM 1352 C HIS A 188 -19. .427 46. .098 54. .501 1. .00 0. .00 XXXX1352

ATOM 1353 O HIS A 188 -18. .920 45. .487 53. .560 1. .00 0. .00 XXXX1353

ATOM 1354 CB HIS A 188 -21. .403 47. .482 53. .798 1. .00 0. .00 XXXX1354

ATOM 1355 CG HIS A 188 -22. .406 47. .116 54. .848 1. .00 0. .00 XXXX1355

ATOM 1356 ND1 HIS A 188 -22. .852 48. .013 55. .795 1. .00 0. .00 XXXX1356

ATOM 1357 CD2 HIS A 188 -23. .059 45. .956 55. .092 1. .00 0. .00 XXXX1357

ATOM 1358 CE1 HIS A 188 -23. .731 47. .419 56. .581 1. .00 0. .00 XXXX1358

ATOM 1359 NE2 HIS A 188 -23. .877 46. .171 56. .176 1. .00 0. .00 XXXX1359

ATOM 1360 N THR A 189 -19. .545 45. .573 55. .718 1. .00 0. .00 XXXX1360

ATOM 1361 CA THR A 189 -18. .996 44. .252 56. .017 1. .00 0. .00 XXXX1361

ATOM 1362 C THR A 189 -19. .981 43. .292 56. .690 1. .00 0. .00 XXXX1362

ATOM 1363 O THR A 189 -19. .711 42. .095 56. .787 1. .00 0. .00 XXXX1363

ATOM 1364 CB THR A 189 -17. .753 44. .369 56. .922 1. .00 0. .00 XXXX1364

ATOM 1365 OG1 THR A 189 -18. .126 44. .954 58. .176 1. .00 0. .00 XXXX1365

ATOM 1366 CG2 THR A 189 -16. .691 45. .235 56. .258 1. .00 0. .00 XXXX1366

ATOM 1367 N ASP A 190 -21. .116 43. .809 57. .151 1. .00 0. .00 XXXX1367

ATOM 1368 CA ASP A 190 -22. .108 42. .972 57. .826 1. .00 0. .00 XXXX1368

ATOM 1369 C ASP A 190 -23. .235 42. .582 56. .873 1. .00 0. .00 XXXX1369

ATOM 1370 O ASP A 190 -24. .123 43. .386 56. .587 1. .00 0. .00 XXXX1370

ATOM 1371 CB ASP A 190 -22. .681 43. .688 59. .050 1. .00 0. .00 XXXX1371

ATOM 1372 CG ASP A 190 -23. .536 42. .776 59. .918 1. .00 0. .00 XXXX1372

ATOM 1373 OD1 ASP A 190 -23. .762 41. .608 59. .532 1. .00 0. .00 XXXX1373

ATOM 1374 OD2 ASP A 190 -23. .991 43. .233 60. .986 1. .00 0. .00 XXXX1374

ATOM 1375 N TYR A 191 -23. .195 41. .347 56. .386 1. .00 0. .00 XXXX1375 Attorney Docket No. 35327-522001 WO

ATOM 1376 CA TYR A 191 -24. .180 40. .877 55. .418 1. .00 0. .00 XXXX1376

ATOM 1377 C TYR A 191 -25. .126 39. .821 55. .987 1. .00 0. .00 XXXX1377

ATOM 1378 O TYR A 191 -25. .791 39. .106 55. .241 1. .00 0. .00 XXXX1378

ATOM 1379 CB TYR A 191 -23. .466 40. .357 54. .170 1. .00 0. .00 XXXX1379

ATOM 1380 CG TYR A 191 -22. .927 41. .497 53. .342 1. .00 0. .00 XXXX1380

ATOM 1381 CD1 TYR A 191 -23. .714 42. .109 52. .377 1. .00 0. .00 XXXX1381

ATOM 1382 CD2 TYR A 191 -21. .651 41. .999 53. .563 1. .00 0. .00 XXXX1382

ATOM 1383 CE1 TYR A 191 -23. .238 43. .170 51. .635 1. .00 0. .00 XXXX1383

ATOM 1384 CE2 TYR A 191 -21. .164 43. .059 52. .826 1. .00 0. .00 XXXX1384

ATOM 1385 CZ TYR A 191 -21. .963 43. .641 51. .863 1. .00 0. .00 XXXX1385

ATOM 1386 OH TYR A 191 -21. .483 44. .698 51. .127 1. .00 0. .00 XXXX1386

ATOM 1387 N SER A 192 -25. .179 39. .728 57. .312 1. .00 0. .00 XXXX1387

ATOM 1388 CA SER A 192 -26. .072 38. .784 57. .973 1. .00 0. .00 XXXX1388

ATOM 1389 C SER A 192 -27. .533 39. .073 57. .630 1. .00 0. .00 XXXX1389

ATOM 1390 O SER A 192 -28. .317 38. .156 57. .386 1. .00 0. .00 XXXX1390

ATOM 1391 CB SER A 192 -25. .867 38. .824 59. .488 1. .00 0. .00 XXXX1391

ATOM 1392 OG SER A 192 -26. .150 40. .111 60. .007 1. .00 0. .00 XXXX1392

ATOM 1393 N SER A 193 -27. .892 40. .353 57. .612 1. .00 0. .00 XXXX1393

ATOM 1394 CA SER A 193 -29. .260 40. .764 57. .311 1. .00 0. .00 XXXX1394

ATOM 1395 C SER A 193 -29. .665 40. .435 55. .874 1. .00 0. .00 XXXX1395

ATOM 1396 O SER A 193 -30. .726 39. .855 55. .637 1. .00 0. .00 XXXX1396

ATOM 1397 CB SER A 193 -29. .432 42. .262 57. .563 1. .00 0. .00 XXXX1397

ATOM 1398 OG SER A 193 -30. .666 42. .724 57. .041 1. .00 0. .00 XXXX1398

ATOM 1399 N VAL A 194 -28. .816 40. .813 54. .923 1. .00 0. .00 XXXX1399

ATOM 1400 CA VAL A 194 -29. .044 40. .507 53. .514 1. .00 0. .00 XXXX1400

ATOM 1401 C VAL A 194 -29. .166 39. .006 53. .267 1. .00 0. .00 XXXX1401

ATOM 1402 O VAL A 194 -30. .076 38. .554 52. .573 1. .00 0. .00 XXXX1402

ATOM 1403 CB VAL A 194 -27. .912 41. .061 52. .625 1. .00 0. .00 XXXX1403

ATOM 1404 CGI VAL A 194 -27. .969 40. .429 51. .243 1. .00 0. .00 XXXX1404

ATOM 1405 CG2 VAL A 194 -27. .996 42. .578 52. .532 1. .00 0. .00 XXXX1405

ATOM 1406 N ILE A 195 -28. .243 38. .238 53. .837 1. .00 0. .00 XXXX1406

ATOM 1407 CA ILE A 195 -28. .229 36. .793 53. .641 1. .00 0. .00 XXXX1407

ATOM 1408 C ILE A 195 -29. .473 36. .136 54. .237 1. .00 0. .00 XXXX1408

ATOM 1409 O ILE A 195 -30. .016 35. .191 53. .664 1. .00 0. .00 XXXX1409

ATOM 1410 CB ILE A 195 -26. .965 36. .159 54. .251 1. .00 0. .00 XXXX1410

ATOM 1411 CGI ILE A 195 -25. .735 36. .547 53. .426 1. .00 0. .00 XXXX1411

ATOM 1412 CG2 ILE A 195 -27. .105 34. .645 54. .317 1. .00 0. .00 XXXX1412

ATOM 1413 CD1 ILE A 195 -24. .418 36. .245 54. .110 1. .00 0. .00 XXXX1413

ATOM 1414 N ASN A 196 -29. .926 36. .636 55. .383 1. .00 0. .00 XXXX1414

ATOM 1415 CA ASN A 196 -31. .165 36. .144 55. .978 1. .00 0. .00 XXXX1415

ATOM 1416 C ASN A 196 -32. .370 36. .409 55. .078 1. .00 0. .00 XXXX1416

ATOM 1417 O ASN A 196 -33. .265 35. .569 54. .965 1. .00 0. .00 XXXX1417

ATOM 1418 CB ASN A 196 -31. .395 36. .773 57. .354 1. .00 0. .00 XXXX1418

ATOM 1419 CG ASN A 196 -30. .561 36. .120 58. .441 1. .00 0. .00 XXXX1419

ATOM 1420 OD1 ASN A 196 -30. .098 34. .989 58. .293 1. .00 0. .00 XXXX1420

ATOM 1421 ND2 ASN A 196 -30. .374 36. .830 59. .547 1. .00 0. .00 XXXX1421

ATOM 1422 N LYS A 197 -32. .392 37. .577 54. .444 1. .00 0. .00 XXXX1422

ATOM 1423 CA LYS A 197 -33. .455 37. .910 53. .500 1. .00 0. .00 XXXX1423

ATOM 1424 C LYS A 197 -33. .392 37. .007 52. .274 1. .00 0. .00 XXXX1424

ATOM 1425 O LYS A 197 -34. .420 36. .546 51. .777 1. .00 0. .00 XXXX1425

ATOM 1426 CB LYS A 197 -33. .371 39. .376 53. .069 1. .00 0. .00 XXXX1426

ATOM 1427 CG LYS A 197 -33. .734 40. .378 54. .149 1. .00 0. .00 XXXX1427

ATOM 1428 CD LYS A 197 -33. .554 41. .799 53. .643 1. .00 0. .00 XXXX1428

ATOM 1429 CE LYS A 197 -33. .879 42. .821 54. .718 1. .00 0. .00 XXXX1429

ATOM 1430 NZ LYS A 197 -33. .574 44. .207 54. .268 1. .00 0. .00 XXXX1430

ATOM 1431 N ILE A 198 -32. .179 36. .768 51. .786 1. .00 0. .00 XXXX1431

ATOM 1432 CA ILE A 198 -31. .969 35. .875 50. .654 1. .00 0. .00 XXXX1432

ATOM 1433 C ILE A 198 -32. .446 34. .464 50. .984 1. .00 0. .00 XXXX1433

ATOM 1434 O ILE A 198 -33. .108 33. .819 50. .171 1. .00 0. .00 XXXX1434

ATOM 1435 CB ILE A 198 -30. .489 35. .839 50. .231 1. .00 0. .00 XXXX1435

ATOM 1436 CGI ILE A 198 -30. .079 37. .185 49. .630 1. .00 0. .00 XXXX1436

ATOM 1437 CG2 ILE A 198 -30. .247 34. .714 49. .236 1. .00 0. .00 XXXX1437

ATOM 1438 CD1 ILE A 198 -28. .617 37. .267 49. .245 1. .00 0. .00 XXXX1438

ATOM 1439 N LYS A 199 -32. .106 33. .989 52. .179 1. .00 0. .00 XXXX1439

ATOM 1440 CA LYS A 199 -32. .557 32. .680 52. .640 1. .00 0. .00 XXXX1440

ATOM 1441 C LYS A 199 -34. .081 32. .581 52. .640 1. .00 0. .00 XXXX1441

ATOM 1442 O LYS A 199 -34. .644 31. .534 52. .317 1. .00 0. .00 XXXX1442 Attorney Docket No. 35327-522001 WO

ATOM 1443 CB LYS A 199 -32. .017 32. .383 54. .042 1. .00 0. .00 XXXX1443

ATOM 1444 CG LYS A 199 -30. .557 31. .965 54. .076 1. .00 0. .00 XXXX1444

ATOM 1445 CD LYS A 199 -30. .125 31. .591 55. .486 1. .00 0. .00 XXXX1445

ATOM 1446 CE LYS A 199 -28. .680 31. .123 55. .514 1. .00 0. .00 XXXX1446

ATOM 1447 NZ LYS A 199 -28. .275 30. .652 56. .868 1. .00 0. .00 XXXX1447

ATOM 1448 N ALA A 200 -34. .743 33. .673 53. .007 1. .00 0. .00 XXXX1448

ATOM 1449 CA ALA A 200 -36. .200 33. .693 53. .077 1. .00 0. .00 XXXX1449

ATOM 1450 C ALA A 200 -36. .829 33. .817 51. .692 1. .00 0. .00 XXXX1450

ATOM 1451 O ALA A 200 -37. .873 33. .228 51. .420 1. .00 0. .00 XXXX1451

ATOM 1452 CB ALA A 200 -36. .670 34. .830 53. .977 1. .00 0. .00 XXXX1452

ATOM 1453 N ALA A 201 -36. .186 34. .584 50. .818 1. .00 0. .00 XXXX1453

ATOM 1454 CA ALA A 201 -36. .736 34. .848 49. .493 1. .00 0. .00 XXXX1454

ATOM 1455 C ALA A 201 -36. .549 33. .662 48. .549 1. .00 0. .00 XXXX1455

ATOM 1456 O ALA A 201 -37. .353 33. .455 47. .640 1. .00 0. .00 XXXX1456

ATOM 1457 CB ALA A 201 -36. .101 36. .096 48. .903 1. .00 0. .00 XXXX1457

ATOM 1458 N LYS A 202 -35. .492 32. .887 48. .776 1. .00 0. .00 XXXX1458

ATOM 1459 CA LYS A 202 -35. .171 31. .729 47. .942 1. .00 0. .00 XXXX1459

ATOM 1460 C LYS A 202 -35. .152 32. .057 46. .448 1. .00 0. .00 XXXX1460

ATOM 1461 O LYS A 202 -35. .895 31. .460 45. .668 1. .00 0. .00 XXXX1461

ATOM 1462 CB LYS A 202 -36. .166 30. .596 48. .210 1. .00 0. .00 XXXX1462

ATOM 1463 CG LYS A 202 -36. .115 30. .050 49. .628 1. .00 0. .00 XXXX1463

ATOM 1464 CD LYS A 202 -37. .124 28. .932 49. .831 1. .00 0. .00 XXXX1464

ATOM 1465 CE LYS A 202 -36. .958 28. .282 51. .195 1. .00 0. .00 XXXX1465

ATOM 1466 NZ LYS A 202 -38. .001 27. .250 51. .455 1. .00 0. .00 XXXX1466

ATOM 1467 N PRO A 203 -34. .296 33. .009 46. .043 1. .00 0. .00 XXXX1467

ATOM 1468 CA PRO A 203 -34. .179 33. .385 44. .630 1. .00 0. .00 XXXX1468

ATOM 1469 C PRO A 203 -33. .510 32. .300 43. .789 1. .00 0. .00 XXXX1469

ATOM 1470 O PRO A 203 -32. .888 31. .395 44. .345 1. .00 0. .00 XXXX1470

ATOM 1471 CB PRO A 203 -33. .314 34. .646 44. .682 1. .00 0. .00 XXXX1471

ATOM 1472 CG PRO A 203 -32. .459 34. .442 45. .891 1. .00 0. .00 XXXX1472

ATOM 1473 CD PRO A 203 -33. .360 33. .767 46. .893 1. .00 0. .00 XXXX1473

ATOM 1474 N ASP A 204 -33. .638 32. .394 42. .468 1. .00 0. .00 XXXX1474

ATOM 1475 CA ASP A 204 -32. .958 31. .469 41. .567 1. .00 0. .00 XXXX1475

ATOM 1476 C ASP A 204 -31. .492 31. .849 41. .428 1. .00 0. .00 XXXX1476

ATOM 1477 O ASP A 204 -30. .628 30. .994 41. .235 1. .00 0. .00 XXXX1477

ATOM 1478 CB ASP A 204 -33. .616 31. .464 40. .184 1. .00 0. .00 XXXX1478

ATOM 1479 CG ASP A 204 -35. .070 31. .051 40. .228 1. .00 0. .00 XXXX1479

ATOM 1480 OD1 ASP A 204 -35. .478 30. .408 41. .217 1. .00 0. .00 XXXX1480

ATOM 1481 OD2 ASP A 204 -35. .801 31. .363 39. .265 1. .00 0. .00 XXXX1481

ATOM 1482 N VAL A 205 -31. .226 33. .145 41. .529 1. .00 0. .00 XXXX1482

ATOM 1483 CA VAL A 205 -29. .891 33. .677 41. .304 1. .00 0. .00 XXXX1483

ATOM 1484 C VAL A 205 -29. .722 35. .024 41. .991 1. .00 0. .00 XXXX1484

ATOM 1485 O VAL A 205 -30. .671 35. .802 42. .105 1. .00 0. .00 XXXX1485

ATOM 1486 CB VAL A 205 -29. .596 33. .837 39. .797 1. .00 0. .00 XXXX1486

ATOM 1487 CGI VAL A 205 -30. .544 34. .853 39. .178 1. .00 0. .00 XXXX1487

ATOM 1488 CG2 VAL A 205 -28. .145 34. .242 39. .568 1. .00 0. .00 XXXX1488

ATOM 1489 N VAL A 206 -28. .511 35. .286 42. .467 1. .00 0. .00 XXXX1489

ATOM 1490 CA VAL A 206 -28. .160 36. .606 42. .963 1. .00 0. .00 XXXX1490

ATOM 1491 C VAL A 206 -27. .350 37. .345 41. .908 1. .00 0. .00 XXXX1491

ATOM 1492 O VAL A 206 -26. .337 36. .837 41. .429 1. .00 0. .00 XXXX1492

ATOM 1493 CB VAL A 206 -27. .349 36. .533 44. .270 1. .00 0. .00 XXXX1493

ATOM 1494 CGI VAL A 206 -26. .982 37. .933 44. .739 1. .00 0. .00 XXXX1494

ATOM 1495 CG2 VAL A 206 -28. .132 35. .793 45. .342 1. .00 0. .00 XXXX1495

ATOM 1496 N PHE A 207 -27. .797 38. .539 41. .534 1. .00 0. .00 XXXX1496

ATOM 1497 CA PHE A 207 -27. .009 39. .357 40. .625 1. .00 0. .00 XXXX1497

ATOM 1498 C PHE A 207 -26. .241 40. .378 41. .450 1. .00 0. .00 XXXX1498

ATOM 1499 O PHE A 207 -26. .816 41. .326 41. .986 1. .00 0. .00 XXXX1499

ATOM 1500 CB PHE A 207 -27. .885 40. .045 39. .575 1. .00 0. .00 XXXX1500

ATOM 1501 CG PHE A 207 -27. .139 40. .407 38. .320 1. .00 0. .00 XXXX1501

ATOM 1502 CD1 PHE A 207 -26. .220 41. .443 38. .319 1. .00 0. .00 XXXX1502

ATOM 1503 CD2 PHE A 207 -27. .341 39. .697 37. .148 1. .00 0. .00 XXXX1503

ATOM 1504 CE1 PHE A 207 -25. .520 41. .770 37. .169 1. .00 0. .00 XXXX1504

ATOM 1505 CE2 PHE A 207 -26. .648 40. .021 35. .993 1. .00 0. .00 XXXX1505

ATOM 1506 CZ PHE A 207 -25. .735 41. .058 36. .005 1. .00 0. .00 XXXX1506

ATOM 1507 N ASN A 208 -24. .933 40. .168 41. .543 1. .00 0. .00 XXXX1507

ATOM 1508 CA ASN A 208 -24. .085 40. .925 42. .454 1. .00 0. .00 XXXX1508

ATOM 1509 C ASN A 208 -23. .383 42. .109 41. .800 1. .00 0. .00 XXXX1509 Attorney Docket No. 35327-522001 WO

ATOM 1510 O ASN A 208 -22. .557 41. .936 40. .903 1. .00 0. .00 XXXX1510

ATOM 1511 CB ASN A 208 -23. .041 39. .996 43. .077 1. .00 0. .00 XXXX1511

ATOM 1512 CG ASN A 208 -22. .045 40. .738 43. .942 1. .00 0. .00 XXXX1512

ATOM 1513 OD1 ASN A 208 -22. .389 41. .716 44. .604 1. .00 0. .00 XXXX1513

ATOM 1514 ND2 ASN A 208 -20. .799 40. .277 43. .940 1. .00 0. .00 XXXX1514

ATOM 1515 N THR A 209 -23. .715 43. .312 42. .258 1. .00 0. .00 XXXX1515

ATOM 1516 CA THR A 209 -23. .037 44. .515 41. .795 1. .00 0. .00 XXXX1516

ATOM 1517 C THR A 209 -22. .267 45. .190 42. .928 1. .00 0. .00 XXXX1517

ATOM 1518 O THR A 209 -21. .977 46. .385 42. .861 1. .00 0. .00 XXXX1518

ATOM 1519 CB THR A 209 -24. .024 45. .526 41. .177 1. .00 0. .00 XXXX1519

ATOM 1520 OG1 THR A 209 -25. .138 45. .712 42. .057 1. .00 0. .00 XXXX1520

ATOM 1521 CG2 THR A 209 -24. .529 45. .024 39. .831 1. .00 0. .00 XXXX1521

ATOM 1522 N LEU A 210 -21. .952 44. .430 43. .974 1. .00 0. .00 XXXX1522

ATOM 1523 CA LEU A 210 -21. .044 44. .915 45. .008 1. .00 0. .00 XXXX1523

ATOM 1524 C LEU A 210 -19. .693 45. .262 44. .394 1. .00 0. .00 XXXX1524

ATOM 1525 O LEU A 210 -19. .185 44. .533 43. .542 1. .00 0. .00 XXXX1525

ATOM 1526 CB LEU A 210 -20. .860 43. .878 46. .121 1. .00 0. .00 XXXX1526

ATOM 1527 CG LEU A 210 -22. .052 43. .540 47. .016 1. .00 0. .00 XXXX1527

ATOM 1528 CD1 LEU A 210 -21. .688 42. .405 47. .963 1. .00 0. .00 XXXX1528

ATOM 1529 CD2 LEU A 210 -22. .502 44. .769 47. .794 1. .00 0. .00 XXXX1529

ATOM 1530 N ASN A 211 -19. .122 46. .380 44. .828 1. .00 0. .00 XXXX1530

ATOM 1531 CA ASN A 211 -17. .793 46. .792 44. .396 1. .00 0. .00 XXXX1531

ATOM 1532 C ASN A 211 -16. .855 46. .916 45. .593 1. .00 0. .00 XXXX1532

ATOM 1533 O ASN A 211 -17. .280 47. .291 46. .684 1. .00 0. .00 XXXX1533

ATOM 1534 CB ASN A 211 -17. .861 48. .118 43. .634 1. .00 0. .00 XXXX1534

ATOM 1535 CG ASN A 211 -18. .240 47. .936 42. .175 1. .00 0. .00 XXXX1535

ATOM 1536 OD1 ASN A 211 -17. .417 48. .133 41. .280 1. .00 0. .00 XXXX1536

ATOM 1537 ND2 ASN A 211 -19. .492 47. .565 41. .927 1. .00 0. .00 XXXX1537

ATOM 1538 N GLY A 212 -15. .581 46. .597 45. .388 1. .00 0. .00 XXXX1538

ATOM 1539 CA GLY A 212 -14. .588 46. .746 46. .438 1. .00 0. .00 XXXX1539

ATOM 1540 C GLY A 212 -14. .615 45. .604 47. .437 1. .00 0. .00 XXXX1540

ATOM 1541 O GLY A 212 -15. .196 44. .553 47. .171 1. .00 0. .00 XXXX1541

ATOM 1542 N ASP A 213 -13. .988 45. .806 48. .592 1. .00 0. .00 XXXX1542

ATOM 1543 CA ASP A 213 -13. .773 44. .708 49. .527 1. .00 0. .00 XXXX1543

ATOM 1544 C ASP A 213 -15. .024 44. .338 50. .328 1. .00 0. .00 XXXX1544

ATOM 1545 O ASP A 213 -14. .963 43. .487 51. .215 1. .00 0. .00 XXXX1545

ATOM 1546 CB ASP A 213 -12. .606 45. .028 50. .474 1. .00 0. .00 XXXX1546

ATOM 1547 CG ASP A 213 -12. .790 46. .331 51. .229 1. .00 0. .00 XXXX1547

ATOM 1548 OD1 ASP A 213 -13. .942 46. .759 51. .445 1. .00 0. .00 XXXX1548

ATOM 1549 OD2 ASP A 213 -11. .762 46. .928 51. .617 1. .00 0. .00 XXXX1549

ATOM 1550 N SER A 214 -16. .150 44. .981 50. .028 1. .00 0. .00 XXXX1550

ATOM 1551 CA SER A 214 -17. .439 44. .489 50. .508 1. .00 0. .00 XXXX1551

ATOM 1552 C SER A 214 -17. .623 43. .043 50. .059 1. .00 0. .00 XXXX1552

ATOM 1553 O SER A 214 -18. .241 42. .239 50. .755 1. .00 0. .00 XXXX1553

ATOM 1554 CB SER A 214 -18. .598 45. .350 49. .992 1. .00 0. .00 XXXX1554

ATOM 1555 OG SER A 214 -18. .804 46. .503 50. .792 1. .00 0. .00 XXXX1555

ATOM 1556 N ASN A 215 -17. .077 42. .726 48. .888 1. .00 0. .00 XXXX1556

ATOM 1557 CA ASN A 215 -17. .169 41. .384 48. .320 1. .00 0. .00 XXXX1557

ATOM 1558 C ASN A 215 -16. .487 40. .325 49. .178 1. .00 0. .00 XXXX1558

ATOM 1559 O ASN A 215 -16. .920 39. .174 49. .218 1. .00 0. .00 XXXX1559

ATOM 1560 CB ASN A 215 -16. .568 41. .365 46. .912 1. .00 0. .00 XXXX1560

ATOM 1561 CG ASN A 215 -17. .489 41. .978 45. .874 1. .00 0. .00 XXXX1561

ATOM 1562 OD1 ASN A 215 -18. .447 41. .347 45. .431 1. .00 0. .00 XXXX1562

ATOM 1563 ND2 ASN A 215 -17. .201 43. .214 45. .479 1. .00 0. .00 XXXX1563

ATOM 1564 N VAL A 216 -15. .415 40. .717 49. .858 1. .00 0. .00 XXXX1564

ATOM 1565 CA VAL A 216 -14. .700 39. .800 50. .735 1. .00 0. .00 XXXX1565

ATOM 1566 C VAL A 216 -15. .616 39. .350 51. .866 1. .00 0. .00 XXXX1566

ATOM 1567 O VAL A 216 -15. .701 38. .162 52. .180 1. .00 0. .00 XXXX1567

ATOM 1568 CB VAL A 216 -13. .436 40. .444 51. .328 1. .00 0. .00 XXXX1568

ATOM 1569 CGI VAL A 216 -12. .771 39. .494 52. .314 1. .00 0. .00 XXXX1569

ATOM 1570 CG2 VAL A 216 -12. .469 40. .837 50. .217 1. .00 0. .00 XXXX1570

ATOM 1571 N ALA A 217 -16. .306 40. .314 52. .466 1. .00 0. .00 XXXX1571

ATOM 1572 CA ALA A 217 -17. .206 40. .042 53. .579 1. .00 0. .00 XXXX1572

ATOM 1573 C ALA A 217 -18. .428 39. .244 53. .135 1. .00 0. .00 XXXX1573

ATOM 1574 O ALA A 217 -18. .841 38. .305 53. .814 1. .00 0. .00 XXXX1574

ATOM 1575 CB ALA A 217 -17. .638 41. .346 54. .240 1. .00 0. .00 XXXX1575

ATOM 1576 N PHE A 218 -19. .006 39. .617 51. .997 1. .00 0. .00 XXXX1576 Attorney Docket No. 35327-522001 WO

ATOM 1577 CA PHE A 218 -20. .240 38. .986 51. .539 1. .00 0. .00 XXXX1577

ATOM 1578 C PHE A 218 -20. .071 37. .496 51. .243 1. .00 0. .00 XXXX1578

ATOM 1579 O PHE A 218 -20. .829 36. .669 51. .750 1. .00 0. .00 XXXX1579

ATOM 1580 CB PHE A 218 -20. .781 39. .688 50. .293 1. .00 0. .00 XXXX1580

ATOM 1581 CG PHE A 218 -21. .935 38. .969 49. .655 1. .00 0. .00 XXXX1581

ATOM 1582 CD1 PHE A 218 -23. .155 38. .880 50. .303 1. .00 0. .00 XXXX1582

ATOM 1583 CD2 PHE A 218 -21. .798 38. .372 48. .412 1. .00 0. .00 XXXX1583

ATOM 1584 CE1 PHE A 218 -24. .219 38. .214 49. .725 1. .00 0. .00 XXXX1584

ATOM 1585 CE2 PHE A 218 -22. .857 37. .704 47. .828 1. .00 0. .00 XXXX1585

ATOM 1586 CZ PHE A 218 -24. .070 37. .627 48. .484 1. .00 0. .00 XXXX1586

ATOM 1587 N PHE A 219 -19. .082 37. .157 50. .422 1. .00 0. .00 XXXX1587

ATOM 1588 CA PHE A 219 -18. .921 35. .779 49. .970 1. .00 0. .00 XXXX1588

ATOM 1589 C PHE A 219 -18. .449 34. .843 51. .078 1. .00 0. .00 XXXX1589

ATOM 1590 O PHE A 219 -18. .822 33. .670 51. .103 1. .00 0. .00 XXXX1590

ATOM 1591 CB PHE A 219 -17. .961 35. .715 48. .781 1. .00 0. .00 XXXX1591

ATOM 1592 CG PHE A 219 -18. .583 36. .148 47. .484 1. .00 0. .00 XXXX1592

ATOM 1593 CD1 PHE A 219 -19. .451 35. .306 46. .809 1. .00 0. .00 XXXX1593

ATOM 1594 CD2 PHE A 219 -18. .305 37. .391 46. .941 1. .00 0. .00 XXXX1594

ATOM 1595 CE1 PHE A 219 -20. .032 35. .694 45. .617 1. .00 0. .00 XXXX1595

ATOM 1596 CE2 PHE A 219 -18. .883 37. .785 45. .746 1. .00 0. .00 XXXX1596

ATOM 1597 CZ PHE A 219 -19. .747 36. .934 45. .084 1. .00 0. .00 XXXX1597

ATOM 1598 N LYS A 220 -17. .635 35. .355 51. .995 1. .00 0. .00 XXXX1598

ATOM 1599 CA LYS A 220 -17. .214 34. .551 53. .133 1. .00 0. .00 XXXX1599

ATOM 1600 C LYS A 220 -18. .417 34. .243 54. .015 1. .00 0. .00 XXXX1600

ATOM 1601 O LYS A 220 -18. .608 33. .107 54. .443 1. .00 0. .00 XXXX1601

ATOM 1602 CB LYS A 220 -16. .119 35. .258 53. .936 1. .00 0. .00 XXXX1602

ATOM 1603 CG LYS A 220 -14. .773 35. .292 53. .231 1. .00 0. .00 XXXX1603

ATOM 1604 CD LYS A 220 -13. .673 35. .827 54. .135 1. .00 0. .00 XXXX1604

ATOM 1605 CE LYS A 220 -12. .350 35. .922 53. .389 1. .00 0. .00 XXXX1605

ATOM 1606 NZ LYS A 220 -11. .265 36. .486 54. .237 1. .00 0. .00 XXXX1606

ATOM 1607 N GLN A 221 -19. .233 35. .258 54. .274 1. .00 0. .00 XXXX1607

ATOM 1608 CA GLN A 221 -20. .415 35. .084 55. .111 1. .00 0. .00 XXXX1608

ATOM 1609 C GLN A 221 -21. .485 34. .259 54. .397 1. .00 0. .00 XXXX1609

ATOM 1610 O GLN A 221 -22. .267 33. .554 55. .037 1. .00 0. .00 XXXX1610

ATOM 1611 CB GLN A 221 -20. .977 36. .444 55. .530 1. .00 0. .00 XXXX1611

ATOM 1612 CG GLN A 221 -20. .173 37. .120 56. .633 1. .00 0. .00 XXXX1612

ATOM 1613 CD GLN A 221 -20. .535 38. .582 56. .811 1. .00 0. .00 XXXX1613

ATOM 1614 OE1 GLN A 221 -21. .712 38. .942 56. .848 1. .00 0. .00 XXXX1614

ATOM 1615 NE2 GLN A 221 -19. .521 39. .434 56. .929 1. .00 0. .00 XXXX1615

ATOM 1616 N LEU A 222 -21. .519 34. .355 53. .071 1. .00 0. .00 XXXX1616

ATOM 1617 CA LEU A 222 -22. .457 33. .570 52. .274 1. .00 0. .00 XXXX1617

ATOM 1618 C LEU A 222 -22. .166 32. .078 52. .417 1. .00 0. .00 XXXX1618

ATOM 1619 O LEU A 222 -23. .074 31. .279 52. .649 1. .00 0. .00 XXXX1619

ATOM 1620 CB LEU A 222 -22. .402 33. .988 50. .800 1. .00 0. .00 XXXX1620

ATOM 1621 CG LEU A 222 -23. .426 33. .332 49. .871 1. .00 0. .00 XXXX1621

ATOM 1622 CD1 LEU A 222 -24. .844 33. .725 50. .262 1. .00 0. .00 XXXX1622

ATOM 1623 CD2 LEU A 222 -23. .150 33. .694 48. .419 1. .00 0. .00 XXXX1623

ATOM 1624 N LYS A 223 -20. .899 31. .705 52. .273 1. .00 0. .00 XXXX1624

ATOM 1625 CA LYS A 223 -20. .494 30. .311 52. .425 1. .00 0. .00 XXXX1625

ATOM 1626 C LYS A 223 -20. .689 29. .817 53. .854 1. .00 0. .00 XXXX1626

ATOM 1627 O LYS A 223 -21. .160 28. .702 54. .079 1. .00 0. .00 XXXX1627

ATOM 1628 CB LYS A 223 -19. .032 30. .128 52. .011 1. .00 0. .00 XXXX1628

ATOM 1629 CG LYS A 223 -18. .544 28. .689 52. .099 1. .00 0. .00 XXXX1629

ATOM 1630 CD LYS A 223 -17. .094 28. .561 51. .657 1. .00 0. .00 XXXX1630

ATOM 1631 CE LYS A 223 -16. .591 27. .132 51. .806 1. .00 0. .00 XXXX1631

ATOM 1632 NZ LYS A 223 -16. .509 26. .712 53. .235 1. .00 0. .00 XXXX1632

ATOM 1633 N ASP A 224 -20. .325 30. .654 54. .819 1. .00 0. .00 XXXX1633

ATOM 1634 CA ASP A 224 -20. .433 30. .285 56. .225 1. .00 0. .00 XXXX1634

ATOM 1635 C ASP A 224 -21. .892 30. .175 56. .655 1. .00 0. .00 XXXX1635

ATOM 1636 O ASP A 224 -22. .207 29. .527 57. .652 1. .00 0. .00 XXXX1636

ATOM 1637 CB ASP A 224 -19. .690 31. .291 57. .105 1. .00 0. .00 XXXX1637

ATOM 1638 CG ASP A 224 -18. .184 31. .211 56. .932 1. .00 0. .00 XXXX1638

ATOM 1639 OD1 ASP A 224 -17. .704 30. .240 56. .308 1. .00 0. .00 XXXX1639

ATOM 1640 OD2 ASP A 224 -17. .479 32. .114 57. .426 1. .00 0. .00 XXXX1640

ATOM 1641 N ALA A 225 -22. .778 30. .813 55. .897 1. .00 0. .00 XXXX1641

ATOM 1642 CA ALA A 225 -24. .208 30. .726 56. .160 1. .00 0. .00 XXXX1642

ATOM 1643 C ALA A 225 -24. .802 29. .459 55. .548 1. .00 0. .00 XXXX1643 Attorney Docket No. 35327-522001 WO

ATOM 1644 O ALA A 225 -26. .008 29. .225 55. .631 1. .00 0. .00 XXXX1644

ATOM 1645 CB ALA A 225 -24. .922 31. .962 55. .628 1. .00 0. .00 XXXX1645

ATOM 1646 N GLY A 226 -23. .952 28. .644 54. .931 1. .00 0. .00 XXXX1646

ATOM 1647 CA GLY A 226 -24. .376 27. .353 54. .419 1. .00 0. .00 XXXX1647

ATOM 1648 C GLY A 226 -24. .905 27. .370 52. .996 1. .00 0. .00 XXXX1648

ATOM 1649 O GLY A 226 -25. .503 26. .395 52. .542 1. .00 0. .00 XXXX1649

ATOM 1650 N ILE A 227 -24. .676 28. .469 52. .286 1. .00 0. .00 XXXX1650

ATOM 1651 CA ILE A 227 -25. .147 28. .601 50. .910 1. .00 0. .00 XXXX1651

ATOM 1652 C ILE A 227 -24. .023 28. .358 49. .904 1. .00 0. .00 XXXX1652

ATOM 1653 O ILE A 227 -23. .001 29. .044 49. .924 1. .00 0. .00 XXXX1653

ATOM 1654 CB ILE A 227 -25. .766 29. .989 50. .663 1. .00 0. .00 XXXX1654

ATOM 1655 CGI ILE A 227 -26. .994 30. .182 51. .556 1. .00 0. .00 XXXX1655

ATOM 1656 CG2 ILE A 227 -26. .136 30. .153 49. .195 1. .00 0. .00 XXXX1656

ATOM 1657 CD1 ILE A 227 -27. .503 31. .608 51. .605 1. .00 0. .00 XXXX1657

ATOM 1658 N ASP A 228 -24. .222 27. .381 49. .022 1. .00 0. .00 XXXX1658

ATOM 1659 CA ASP A 228 -23. .233 27. .064 47. .995 1. .00 0. .00 XXXX1659

ATOM 1660 C ASP A 228 -23. .696 27. .490 46. .603 1. .00 0. .00 XXXX1660

ATOM 1661 O ASP A 228 -24. .862 27. .835 46. .406 1. .00 0. .00 XXXX1661

ATOM 1662 CB ASP A 228 -22. .928 25. .565 48. .001 1. .00 0. .00 XXXX1662

ATOM 1663 CG ASP A 228 -24. .138 24. .724 47. .639 1. .00 0. .00 XXXX1663

ATOM 1664 OD1 ASP A 228 -24. .321 24. .431 46. .439 1. .00 0. .00 XXXX1664

ATOM 1665 OD2 ASP A 228 -24. .908 24. .358 48. .553 1. .00 0. .00 XXXX1665

ATOM 1666 N ALA A 229 -22. .774 27. .461 45. .643 1. .00 0. .00 XXXX1666

ATOM 1667 CA ALA A 229 -23. .041 27. .969 44. .300 1. .00 0. .00 XXXX1667

ATOM 1668 C ALA A 229 -24. .084 27. .157 43. .528 1. .00 0. .00 XXXX1668

ATOM 1669 O ALA A 229 -24. .774 27. .696 42. .663 1. .00 0. .00 XXXX1669

ATOM 1670 CB ALA A 229 -21. .739 28. .033 43. .507 1. .00 0. .00 XXXX1670

ATOM 1671 N ASN A 230 -24. .204 25. .871 43. .841 1. .00 0. .00 XXXX1671

ATOM 1672 CA ASN A 230 -25. .213 25. .025 43. .204 1. .00 0. .00 XXXX1672

ATOM 1673 C ASN A 230 -26. .613 25. .354 43. .700 1. .00 0. .00 XXXX1673

ATOM 1674 O ASN A 230 -27. .565 25. .398 42. .921 1. .00 0. .00 XXXX1674

ATOM 1675 CB ASN A 230 -24. .908 23. .543 43. .425 1. .00 0. .00 XXXX1675

ATOM 1676 CG ASN A 230 -23. .755 23. .058 42. .570 1. .00 0. .00 XXXX1676

ATOM 1677 OD1 ASN A 230 -23. .588 23. .500 41. .433 1. .00 0. .00 XXXX1677

ATOM 1678 ND2 ASN A 230 -22. .964 22. .135 43. .104 1. .00 0. .00 XXXX1678

ATOM 1679 N THR A 231 -26. .730 25. .596 45. .000 1. .00 0. .00 XXXX1679

ATOM 1680 CA THR A 231 -28. .015 25. .927 45. .596 1. .00 0. .00 XXXX1680

ATOM 1681 C THR A 231 -28. .431 27. .335 45. .188 1. .00 0. .00 XXXX1681

ATOM 1682 O THR A 231 -29. .597 27. .582 44. .883 1. .00 0. .00 XXXX1682

ATOM 1683 CB THR A 231 -27. .969 25. .825 47. .132 1. .00 0. .00 XXXX1683

ATOM 1684 OG1 THR A 231 -27. .499 24. .526 47. .515 1. .00 0. .00 XXXX1684

ATOM 1685 CG2 THR A 231 -29. .352 26. .054 47. .725 1. .00 0. .00 XXXX1685

ATOM 1686 N LEU A 232 -27. .476 28. .258 45. .187 1. .00 0. .00 XXXX1686

ATOM 1687 CA LEU A 232 -27. .761 29. .635 44. .805 1. .00 0. .00 XXXX1687

ATOM 1688 C LEU A 232 -26. .567 30. .253 44. .089 1. .00 0. .00 XXXX1688

ATOM 1689 O LEU A 232 -25. .644 30. .751 44. .732 1. .00 0. .00 XXXX1689

ATOM 1690 CB LEU A 232 -28. .130 30. .468 46. .034 1. .00 0. .00 XXXX1690

ATOM 1691 CG LEU A 232 -28. .441 31. .941 45. .773 1. .00 0. .00 XXXX1691

ATOM 1692 CD1 LEU A 232 -29. .554 32. .070 44. .744 1. .00 0. .00 XXXX1692

ATOM 1693 CD2 LEU A 232 -28. .810 32. .654 47. .066 1. .00 0. .00 XXXX1693

ATOM 1694 N PRO A 233 -26. .584 30. .225 42. .750 1. .00 0. .00 XXXX1694

ATOM 1695 CA PRO A 233 -25. .487 30. .825 41. .986 1. .00 0. .00 XXXX1695

ATOM 1696 C PRO A 233 -25. .478 32. .345 42. .101 1. .00 0. .00 XXXX1696

ATOM 1697 O PRO A 233 -26. .537 32. .974 42. .095 1. .00 0. .00 XXXX1697

ATOM 1698 CB PRO A 233 -25. .770 30. .383 40. .546 1. .00 0. .00 XXXX1698

ATOM 1699 CG PRO A 233 -27. .215 30. .022 40. .520 1. .00 0. .00 XXXX1699

ATOM 1700 CD PRO A 233 -27. .562 29. .537 41. .891 1. .00 0. .00 XXXX1700

ATOM 1701 N VAL A 234 -24. .286 32. .920 42. .210 1. .00 0. .00 XXXX1701

ATOM 1702 CA VAL A 234 -24. .125 34. .368 42. .219 1. .00 0. .00 XXXX1702

ATOM 1703 C VAL A 234 -23. .410 34. .833 40. .956 1. .00 0. .00 XXXX1703

ATOM 1704 O VAL A 234 -22. .288 34. .411 40. .679 1. .00 0. .00 XXXX1704

ATOM 1705 CB VAL A 234 -23. .334 34. .842 43. .455 1. .00 0. .00 XXXX1705

ATOM 1706 CGI VAL A 234 -23. .134 36. .349 43. .413 1. .00 0. .00 XXXX1706

ATOM 1707 CG2 VAL A 234 -24. .044 34. .422 44. .734 1. .00 0. .00 XXXX1707

ATOM 1708 N MET A 235 -24. .065 35. .698 40. .189 1. .00 0. .00 XXXX1708

ATOM 1709 CA MET A 235 -23. .438 36. .302 39. .021 1. .00 0. .00 XXXX1709

ATOM 1710 C MET A 235 -22. .902 37. .684 39. .378 1. .00 0. .00 XXXX1710 Attorney Docket No. 35327-522001 WO

ATOM 1711 O MET A 235 -23. .659 38. .564 39. .788 1. .00 0. .00 XXXX1711

ATOM 1712 CB MET A 235 -24. .430 36. .393 37. .859 1. .00 0. .00 XXXX1712

ATOM 1713 CG MET A 235 -23. .920 37. .176 36. .657 1. .00 0. .00 XXXX1713

ATOM 1714 SD MET A 235 -22. .586 36. .339 35. .777 1. .00 0. .00 XXXX1714

ATOM 1715 CE MET A 235 -23. .498 35. .071 34. .901 1. .00 0. .00 XXXX1715

ATOM 1716 N SER A 236 -21. .594 37. .868 39. .223 1. .00 0. .00 XXXX1716

ATOM 1717 CA SER A 236 -20. .941 39. .124 39. .577 1. .00 0. .00 XXXX1717

ATOM 1718 C SER A 236 -20. .386 39. .826 38. .342 1. .00 0. .00 XXXX1718

ATOM 1719 O SER A 236 -19. .966 39. .174 37. .385 1. .00 0. .00 XXXX1719

ATOM 1720 CB SER A 236 -19. .822 38. .877 40. .592 1. .00 0. .00 XXXX1720

ATOM 1721 OG SER A 236 -20. .340 38. .356 41. .803 1. .00 0. .00 XXXX1721

ATOM 1722 N VAL A 237 -20. .388 41. .155 38. .365 1. .00 0. .00 XXXX1722

ATOM 1723 CA VAL A 237 -19. .887 41. .931 37. .236 1. .00 0. .00 XXXX1723

ATOM 1724 C VAL A 237 -18. .811 42. .943 37. .627 1. .00 0. .00 XXXX1724

ATOM 1725 O VAL A 237 -18. .301 43. .667 36. .774 1. .00 0. .00 XXXX1725

ATOM 1726 CB VAL A 237 -21. .033 42. .688 36. .532 1. .00 0. .00 XXXX1726

ATOM 1727 CGI VAL A 237 -21. .972 41. .707 35. .840 1. .00 0. .00 XXXX1727

ATOM 1728 CG2 VAL A 237 -21. .791 43. .556 37. .529 1. .00 0. .00 XXXX1728

ATOM 1729 N SER A 238 -18. .454 42. .988 38. .907 1. .00 0. .00 XXXX1729

ATOM 1730 CA SER A 238 -17. .451 43. .947 39. .362 1. .00 0. .00 XXXX1730

ATOM 1731 C SER A 238 -16. .319 43. .283 40. .139 1. .00 0. .00 XXXX1731

ATOM 1732 O SER A 238 -15. .515 43. .961 40. .782 1. .00 0. .00 XXXX1732

ATOM 1733 CB SER A 238 -18. .104 45. .037 40. .213 1. .00 0. .00 XXXX1733

ATOM 1734 OG SER A 238 -19. .073 45. .751 39. .462 1. .00 0. .00 XXXX1734

ATOM 1735 N ILE A 239 -16. .259 41. .957 40. .078 1. .00 0. .00 XXXX1735

ATOM 1736 CA ILE A 239 -15. .098 41. .223 40. .569 1. .00 0. .00 XXXX1736

ATOM 1737 C ILE A 239 -14. .612 40. .239 39. .512 1. .00 0. .00 XXXX1737

ATOM 1738 O ILE A 239 -15. .405 39. .702 38. .739 1. .00 0. .00 XXXX1738

ATOM 1739 CB ILE A 239 -15. .399 40. .459 41. .873 1. .00 0. .00 XXXX1739

ATOM 1740 CGI ILE A 239 -16. .530 39. .450 41. .661 1. .00 0. .00 XXXX1740

ATOM 1741 CG2 ILE A 239 -15. .723 41. .432 42. .999 1. .00 0. .00 XXXX1741

ATOM 1742 CD1 ILE A 239 -16. .622 38. .404 42. .752 1. .00 0. .00 XXXX1742

ATOM 1743 N ALA A 240 -13. .304 40. .010 39. .485 1. .00 0. .00 XXXX1743

ATOM 1744 CA ALA A 240 -12. .706 39. .049 38. .566 1. .00 0. .00 XXXX1744

ATOM 1745 C ALA A 240 -11. .561 38. .319 39. .262 1. .00 0. .00 XXXX1745

ATOM 1746 O ALA A 240 -11. .529 38. .246 40. .491 1. .00 0. .00 XXXX1746

ATOM 1747 CB ALA A 240 -12. .219 39. .744 37. .303 1. .00 0. .00 XXXX1747

ATOM 1748 N GLU A 241 -10. .622 37. .789 38. .482 1. .00 0. .00 XXXX1748

ATOM 1749 CA GLU A 241 -9. .553 36. .949 39. .025 1. .00 0. .00 XXXX1749

ATOM 1750 C GLU A 241 -8. .781 37. .597 40. .177 1. .00 0. .00 XXXX1750

ATOM 1751 O GLU A 241 -8. .388 36. .915 41. .125 1. .00 0. .00 XXXX1751

ATOM 1752 CB GLU A 241 -8. .569 36. .552 37. .920 1. .00 0. .00 XXXX1752

ATOM 1753 CG GLU A 241 -9. .081 35. .474 36. .974 1. .00 0. .00 XXXX1753

ATOM 1754 CD GLU A 241 -9. .751 36. .035 35. .734 1. .00 0. .00 XXXX1754

ATOM 1755 OE1 GLU A 241 -10. .364 37. .121 35. .817 1. .00 0. .00 XXXX1755

ATOM 1756 OE2 GLU A 241 -9. .656 35. .387 34. .669 1. .00 0. .00 XXXX1756

ATOM 1757 N GLU A 242 -8. .563 38. .905 40. .096 1. .00 0. .00 XXXX1757

ATOM 1758 CA GLU A 242 -7. .810 39. .608 41. .131 1. .00 0. .00 XXXX1758

ATOM 1759 C GLU A 242 -8. .542 39. .586 42. .471 1. .00 0. .00 XXXX1759

ATOM 1760 O GLU A 242 -7. .970 39. .203 43. .492 1. .00 0. .00 XXXX1760

ATOM 1761 CB GLU A 242 -7. .532 41. .053 40. .709 1. .00 0. .00 XXXX1761

ATOM 1762 CG GLU A 242 -6. .836 41. .893 41. .773 1. .00 0. .00 XXXX1762

ATOM 1763 CD GLU A 242 -5. .398 41. .467 42. .019 1. .00 0. .00 XXXX1763

ATOM 1764 OE1 GLU A 242 -4. .891 40. .600 41. .276 1. .00 0. .00 XXXX1764

ATOM 1765 OE2 GLU A 242 -4. .770 42. .007 42. .953 1. .00 0. .00 XXXX1765

ATOM 1766 N GLU A 243 -9. .810 39. .990 42. .463 1. .00 0. .00 XXXX1766

ATOM 1767 CA GLU A 243 -10. .611 40. .017 43. .684 1. .00 0. .00 XXXX1767

ATOM 1768 C GLU A 243 -10. .901 38. .610 44. .192 1. .00 0. .00 XXXX1768

ATOM 1769 O GLU A 243 -10. .992 38. .383 45. .399 1. .00 0. .00 XXXX1769

ATOM 1770 CB GLU A 243 -11. .927 40. .764 43. .454 1. .00 0. .00 XXXX1770

ATOM 1771 CG GLU A 243 -11. .767 42. .223 43. .067 1. .00 0. .00 XXXX1771

ATOM 1772 CD GLU A 243 -11. .385 42. .405 41. .610 1. .00 0. .00 XXXX1772

ATOM 1773 OE1 GLU A 243 -11. .415 41. .408 40. .857 1. .00 0. .00 XXXX1773

ATOM 1774 OE2 GLU A 243 -11. .059 43. .547 41. .220 1. .00 0. .00 XXXX1774

ATOM 1775 N ILE A 244 -11. .055 37. .669 43. .266 1. .00 0. .00 XXXX1775

ATOM 1776 CA ILE A 244 -11. .300 36. .278 43. .626 1. .00 0. .00 XXXX1776

ATOM 1777 C ILE A 244 -10. .139 35. .729 44. .450 1. .00 0. .00 XXXX1777 Attorney Docket No. 35327-522001 WO

ATOM 1778 O ILE A 244 -10. .345 34. .992 45. .413 1. .00 0. .00 XXXX1778

ATOM 1779 CB ILE A 244 -11. .517 35. .400 42. .382 1. .00 0. .00 XXXX1779

ATOM 1780 CGI ILE A 244 -12. .861 35. .737 41. .728 1. .00 0. .00 XXXX1780

ATOM 1781 CG2 ILE A 244 -11. .474 33. .929 42. .759 1. .00 0. .00 XXXX1781

ATOM 1782 CD1 ILE A 244 -13. .055 35. .109 40. .363 1. .00 0. .00 XXXX1782

ATOM 1783 N LYS A 245 -8. .920 36. .091 44. .065 1. .00 0. .00 XXXX1783

ATOM 1784 CA LYS A 245 -7. .735 35. .695 44. .819 1. .00 0. .00 XXXX1784

ATOM 1785 C LYS A 245 -7. .694 36. .378 46. .185 1. .00 0. .00 XXXX1785

ATOM 1786 O LYS A 245 -7. .275 35. .780 47. .176 1. .00 0. .00 XXXX1786

ATOM 1787 CB LYS A 245 -6. .465 36. .018 44. .029 1. .00 0. .00 XXXX1787

ATOM 1788 CG LYS A 245 -5. .854 34. .822 43. .323 1. .00 0. .00 XXXX1788

ATOM 1789 CD LYS A 245 -5. .494 33. .729 44. .315 1. .00 0. .00 XXXX1789

ATOM 1790 CE LYS A 245 -4. .783 32. .572 43. .631 1. .00 0. .00 XXXX1790

ATOM 1791 NZ LYS A 245 -4. .438 31. .486 44. .590 1. .00 0. .00 XXXX1791

ATOM 1792 N GLY A 246 -8. .126 37. .634 46. .227 1. .00 0. .00 XXXX1792

ATOM 1793 CA GLY A 246 -8. .163 38. .383 47. .469 1. .00 0. .00 XXXX1793

ATOM 1794 C GLY A 246 -9. .204 37. .845 48. .432 1. .00 0. .00 XXXX1794

ATOM 1795 O GLY A 246 -8. .955 37. .725 49. .631 1. .00 0. .00 XXXX1795

ATOM 1796 N ILE A 247 -10. .378 37. .521 47. .900 1. .00 0. .00 XXXX1796

ATOM 1797 CA ILE A 247 -11. .468 36. .985 48. .707 1. .00 0. .00 XXXX1797

ATOM 1798 C ILE A 247 -11. .163 35. .563 49. .157 1. .00 0. .00 XXXX1798

ATOM 1799 O ILE A 247 -11. .462 35. .176 50. .287 1. .00 0. .00 XXXX1799

ATOM 1800 CB ILE A 247 -12. .800 36. .987 47. .932 1. .00 0. .00 XXXX1800

ATOM 1801 CGI ILE A 247 -13. .170 38. .407 47. .500 1. .00 0. .00 XXXX1801

ATOM 1802 CG2 ILE A 247 -13. .911 36. .371 48. .772 1. .00 0. .00 XXXX1802

ATOM 1803 CD1 ILE A 247 -14. .309 38. .459 46. .502 1. .00 0. .00 XXXX1803

ATOM 1804 N GLY A 248 -10. .561 34. .790 48. .258 1. .00 0. .00 XXXX1804

ATOM 1805 CA GLY A 248 -10. .321 33. .380 48. .493 1. .00 0. .00 XXXX1805

ATOM 1806 C GLY A 248 -11. .210 32. .555 47. .584 1. .00 0. .00 XXXX1806

ATOM 1807 O GLY A 248 -12. .432 32. .574 47. .726 1. .00 0. .00 XXXX1807

ATOM 1808 N PRO A 249 -10. .601 31. .834 46. .631 1. .00 0. .00 XXXX1808

ATOM 1809 CA PRO A 249 -11. .335 31. .017 45. .657 1. .00 0. .00 XXXX1809

ATOM 1810 C PRO A 249 -12. .268 29. .997 46. .306 1. .00 0. .00 XXXX1810

ATOM 1811 O PRO A 249 -13. .252 29. .592 45. .688 1. .00 0. .00 XXXX1811

ATOM 1812 CB PRO A 249 -10. .215 30. .311 44. .884 1. .00 0. .00 XXXX1812

ATOM 1813 CG PRO A 249 -9. .046 31. .226 45. .008 1. .00 0. .00 XXXX1813

ATOM 1814 CD PRO A 249 -9. .148 31. .801 46. .392 1. .00 0. .00 XXXX1814

ATOM 1815 N GLU A 250 -11. .968 29. .597 47. .538 1. .00 0. .00 XXXX1815

ATOM 1816 CA GLU A 250 -12. .795 28. .622 48. .243 1. .00 0. .00 XXXX1816

ATOM 1817 C GLU A 250 -14. .206 29. .151 48. .499 1. .00 0. .00 XXXX1817

ATOM 1818 O GLU A 250 -15. .149 28. .377 48. .669 1. .00 0. .00 XXXX1818

ATOM 1819 CB GLU A 250 -12. .135 28. .212 49. .563 1. .00 0. .00 XXXX1819

ATOM 1820 CG GLU A 250 -12. .074 29. .308 50. .612 1. .00 0. .00 XXXX1820

ATOM 1821 CD GLU A 250 -11. .367 28. .857 51. .877 1. .00 0. .00 XXXX1821

ATOM 1822 OE1 GLU A 250 -11. .948 28. .043 52. .625 1. .00 0. .00 XXXX1822

ATOM 1823 OE2 GLU A 250 -10. .232 29. .317 52. .124 1. .00 0. .00 XXXX1823

ATOM 1824 N TYR A 251 -14. .347 30. .472 48. .530 1. .00 0. .00 XXXX1824

ATOM 1825 CA TYR A 251 -15. .650 31. .094 48. .740 1. .00 0. .00 XXXX1825

ATOM 1826 C TYR A 251 -16. .353 31. .423 47. .424 1. .00 0. .00 XXXX1826

ATOM 1827 O TYR A 251 -17. .524 31. .805 47. .417 1. .00 0. .00 XXXX1827

ATOM 1828 CB TYR A 251 -15. .505 32. .363 49. .582 1. .00 0. .00 XXXX1828

ATOM 1829 CG TYR A 251 -14. .883 32. .131 50. .941 1. .00 0. .00 XXXX1829

ATOM 1830 CD1 TYR A 251 -15. .606 31. .529 51. .963 1. .00 0. .00 XXXX1830

ATOM 1831 CD2 TYR A 251 -13. .576 32. .517 51. .204 1. .00 0. .00 XXXX1831

ATOM 1832 CE1 TYR A 251 -15. .044 31. .315 53. .208 1. .00 0. .00 XXXX1832

ATOM 1833 CE2 TYR A 251 -13. .004 32. .307 52. .447 1. .00 0. .00 XXXX1833

ATOM 1834 CZ TYR A 251 -13. .743 31. .706 53. .445 1. .00 0. .00 XXXX1834

ATOM 1835 OH TYR A 251 -13. .178 31. .496 54. .682 1. .00 0. .00 XXXX1835

ATOM 1836 N LEU A 252 -15. .637 31. .269 46. .314 1. .00 0. .00 XXXX1836

ATOM 1837 CA LEU A 252 -16. .146 31. .686 45. .009 1. .00 0. .00 XXXX1837

ATOM 1838 C LEU A 252 -16. .337 30. .527 44. .037 1. .00 0. .00 XXXX1838

ATOM 1839 O LEU A 252 -16. .962 30. .692 42. .989 1. .00 0. .00 XXXX1839

ATOM 1840 CB LEU A 252 -15. .214 32. .724 44. .379 1. .00 0. .00 XXXX1840

ATOM 1841 CG LEU A 252 -15. .480 34. .187 44. .736 1. .00 0. .00 XXXX1841

ATOM 1842 CD1 LEU A 252 -16. .866 34. .598 44. .261 1. .00 0. .00 XXXX1842

ATOM 1843 CD2 LEU A 252 -15. .334 34. .417 46. .229 1. .00 0. .00 XXXX1843

ATOM 1844 N LYS A 253 -15. .784 29. .365 44. .377 1. .00 0. .00 XXXX1844 Attorney Docket No. 35327-522001 WO

ATOM 1845 CA LYS A 253 -15. .824 28. .206 43. .489 1. .00 0. .00 XXXX1845

ATOM 1846 C LYS A 253 -17. .249 27. .889 43. .038 1. .00 0. .00 XXXX1846

ATOM 1847 O LYS A 253 -18. .145 27. .701 43. .861 1. .00 0. .00 XXXX1847

ATOM 1848 CB LYS A 253 -15. .209 26. .988 44. .184 1. .00 0. .00 XXXX1848

ATOM 1849 CG LYS A 253 -15. .139 25. .734 43. .323 1. .00 0. .00 XXXX1849

ATOM 1850 CD LYS A 253 -14. .615 24. .549 44. .126 1. .00 0. .00 XXXX1850

ATOM 1851 CE LYS A 253 -14. .589 23. .273 43. .299 1. .00 0. .00 XXXX1851

ATOM 1852 NZ LYS A 253 -15. .961 22. .811 42. .952 1. .00 0. .00 XXXX1852

ATOM 1853 N GLY A 254 -17. .447 27. .834 41. .725 1. .00 0. .00 XXXX1853

ATOM 1854 CA GLY A 254 -18. .740 27. .495 41. .158 1. .00 0. .00 XXXX1854

ATOM 1855 C GLY A 254 -19. .612 28. .689 40. .815 1. .00 0. .00 XXXX1855

ATOM 1856 O GLY A 254 -20. .572 28. .560 40. .054 1. .00 0. .00 XXXX1856

ATOM 1857 N HIS A 255 -19. .284 29. .855 41. .365 1. .00 0. .00 XXXX1857

ATOM 1858 CA HIS A 255 -20. .053 31. .063 41. .075 1. .00 0. .00 XXXX1858

ATOM 1859 C HIS A 255 -19. .683 31. .633 39. .708 1. .00 0. .00 XXXX1859

ATOM 1860 O HIS A 255 -18. .738 31. .170 39. .069 1. .00 0. .00 XXXX1860

ATOM 1861 CB HIS A 255 -19. .850 32. .106 42. .177 1. .00 0. .00 XXXX1861

ATOM 1862 CG HIS A 255 -20. .567 31. .777 43. .451 1. .00 0. .00 XXXX1862

ATOM 1863 ND1 HIS A 255 -21. .939 31. .670 43. .524 1. .00 0. .00 XXXX1863

ATOM 1864 CD2 HIS A 255 -20. .102 31. .522 44. .696 1. .00 0. .00 XXXX1864

ATOM 1865 CE1 HIS A 255 -22. .290 31. .366 44. .761 1. .00 0. .00 XXXX1865

ATOM 1866 NE2 HIS A 255 -21. .194 31. .273 45. .493 1. .00 0. .00 XXXX1866

ATOM 1867 N LEU A 256 -20. .426 32. .645 39. .268 1. .00 0. .00 XXXX1867

ATOM 1868 CA LEU A 256 -20. .380 33. .071 37. .872 1. .00 0. .00 XXXX1868

ATOM 1869 C LEU A 256 -19. .924 34. .515 37. .682 1. .00 0. .00 XXXX1869

ATOM 1870 O LEU A 256 -20. .129 35. .368 38. .546 1. .00 0. .00 XXXX1870

ATOM 1871 CB LEU A 256 -21. .758 32. .887 37. .232 1. .00 0. .00 XXXX1871

ATOM 1872 CG LEU A 256 -22. .368 31. .489 37. .346 1. .00 0. .00 XXXX1872

ATOM 1873 CD1 LEU A 256 -23. .807 31. .487 36. .853 1. .00 0. .00 XXXX1873

ATOM 1874 CD2 LEU A 256 -21. .533 30. .469 36. .582 1. .00 0. .00 XXXX1874

ATOM 1875 N VAL A 257 -19. .304 34. .778 36. .535 1. .00 0. .00 XXXX1875

ATOM 1876 CA VAL A 257 -18. .925 36. .133 36. .155 1. .00 0. .00 XXXX1876

ATOM 1877 C VAL A 257 -19. .212 36. .389 34. .680 1. .00 0. .00 XXXX1877

ATOM 1878 O VAL A 257 -19. .292 35. .456 33. .882 1. .00 0. .00 XXXX1878

ATOM 1879 CB VAL A 257 -17. .432 36. .404 36. .419 1. .00 0. .00 XXXX1879

ATOM 1880 CGI VAL A 257 -17. .120 36. .276 37. .901 1. .00 0. .00 XXXX1880

ATOM 1881 CG2 VAL A 257 -16. .568 35. .456 35. .601 1. .00 0. .00 XXXX1881

ATOM 1882 N THR A 258 -19. .369 37. .660 34. .328 1. .00 0. .00 XXXX1882

ATOM 1883 CA THR A 258 -19. .444 38. .064 32. .931 1. .00 0. .00 XXXX1883

ATOM 1884 C THR A 258 -18. .443 39. .179 32. .670 1. .00 0. .00 XXXX1884

ATOM 1885 O THR A 258 -18. .433 40. .191 33. .369 1. .00 0. .00 XXXX1885

ATOM 1886 CB THR A 258 -20. .856 38. .539 32. .538 1. .00 0. .00 XXXX1886

ATOM 1887 OG1 THR A 258 -21. .800 37. .487 32. .775 1. .00 0. .00 XXXX1887

ATOM 1888 CG2 THR A 258 -20. .896 38. .926 31. .065 1. .00 0. .00 XXXX1888

ATOM 1889 N TRP A 259 -17. .604 38. .986 31. .659 1. .00 0. .00 XXXX1889

ATOM 1890 CA TRP A 259 -16. .571 39. .955 31. .320 1. .00 0. .00 XXXX1890

ATOM 1891 C TRP A 259 -16. .281 39. .912 29. .826 1. .00 0. .00 XXXX1891

ATOM 1892 O TRP A 259 -17. .011 39. .283 29. .060 1. .00 0. .00 XXXX1892

ATOM 1893 CB TRP A 259 -15. .286 39. .681 32. .106 1. .00 0. .00 XXXX1893

ATOM 1894 CG TRP A 259 -15. .380 39. .970 33. .576 1. .00 0. .00 XXXX1894

ATOM 1895 CD1 TRP A 259 -15. .583 39. .064 34. .578 1. .00 0. .00 XXXX1895

ATOM 1896 CD2 TRP A 259 -15. .264 41. .250 34. .212 1. .00 0. .00 XXXX1896

ATOM 1897 NE1 TRP A 259 -15. .604 39. .701 35. .795 1. .00 0. .00 XXXX1897

ATOM 1898 CE2 TRP A 259 -15. .410 41. .043 35. .598 1. .00 0. .00 XXXX1898

ATOM 1899 CE3 TRP A 259 -15. .053 42. .550 33. .744 1. .00 0. .00 XXXX1899

ATOM 1900 CZ2 TRP A 259 -15. .351 42. .087 36. .520 1. .00 0. .00 XXXX1900

ATOM 1901 CZ3 TRP A 259 -14. .993 43. .585 34. .660 1. .00 0. .00 XXXX1901

ATOM 1902 CH2 TRP A 259 -15. .142 43. .347 36. .032 1. .00 0. .00 XXXX1902

ATOM 1903 N ASN A 260 -15. .210 40. .582 29. .417 1. .00 0. .00 XXXX1903

ATOM 1904 CA ASN A 260 -14. .775 40. .545 28. .029 1. .00 0. .00 XXXX1904

ATOM 1905 C ASN A 260 -13. .469 39. .777 27. .918 1. .00 0. .00 XXXX1905

ATOM 1906 O ASN A 260 -12. .983 39. .499 26. .821 1. .00 0. .00 XXXX1906

ATOM 1907 CB ASN A 260 -14. .605 41. .959 27. .479 1. .00 0. .00 XXXX1907

ATOM 1908 CG ASN A 260 -15. .828 42. .822 27. .706 1. .00 0. .00 XXXX1908

ATOM 1909 OD1 ASN A 260 -15. .755 43. .857 28. .366 1. .00 0. .00 XXXX1909

ATOM 1910 ND2 ASN A 260 -16. .964 42. .398 27. .162 1. .00 0. .00 XXXX1910

ATOM 1911 N TYR A 261 -12. .913 39. .436 29. .075 1. .00 0. .00 XXXX1911 Attorney Docket No. 35327-522001 WO

ATOM 1912 CA TYR A 261 -11. .596 38. .822 29. .162 1. .00 0. .00 XXXX1912

ATOM 1913 C TYR A 261 -11. .459 37. .968 30. .416 1. .00 0. .00 XXXX1913

ATOM 1914 O TYR A 261 -11. .938 38. .341 31. .488 1. .00 0. .00 XXXX1914

ATOM 1915 CB TYR A 261 -10. .505 39. .900 29. .143 1. .00 0. .00 XXXX1915

ATOM 1916 CG TYR A 261 -9. .117 39. .394 29. .488 1. .00 0. .00 XXXX1916

ATOM 1917 CD1 TYR A 261 -8. .680 39. .347 30. .808 1. .00 0. .00 XXXX1917

ATOM 1918 CD2 TYR A 261 -8. .241 38. .973 28. .495 1. .00 0. .00 XXXX1918

ATOM 1919 CE1 TYR A 261 -7. .416 38. .888 31. .129 1. .00 0. .00 XXXX1919

ATOM 1920 CE2 TYR A 261 -6. .972 38. .513 28. .809 1. .00 0. .00 XXXX1920

ATOM 1921 CZ TYR A 261 -6. .566 38. .474 30. .126 1. .00 0. .00 XXXX1921

ATOM 1922 OH TYR A 261 -5. .307 38. .019 30. .448 1. .00 0. .00 XXXX1922

ATOM 1923 N PHE A 262 -10. .795 36. .827 30. .266 1. .00 0. .00 XXXX1923

ATOM 1924 CA PHE A 262 -10. .361 36. .009 31. .393 1. .00 0. .00 XXXX1924

ATOM 1925 C PHE A 262 -8. .869 35. .755 31. .224 1. .00 0. .00 XXXX1925

ATOM 1926 O PHE A 262 -8. .363 35. .755 30. .101 1. .00 0. .00 XXXX1926

ATOM 1927 CB PHE A 262 -11. .113 34. .673 31. .459 1. .00 0. .00 XXXX1927

ATOM 1928 CG PHE A 262 -12. .611 34. .805 31. .456 1. .00 0. .00 XXXX1928

ATOM 1929 CD1 PHE A 262 -13. .245 35. .756 32. .237 1. .00 0. .00 XXXX1929

ATOM 1930 CD2 PHE A 262 -13. .387 33. .961 30. .677 1. .00 0. .00 XXXX1930

ATOM 1931 CE1 PHE A 262 -14. .624 35. .871 32. .231 1. .00 0. .00 XXXX1931

ATOM 1932 CE2 PHE A 262 -14. .766 34. .069 30. .670 1. .00 0. .00 XXXX1932

ATOM 1933 CZ PHE A 262 -15. .385 35. .025 31. .447 1. .00 0. .00 XXXX1933

ATOM 1934 N GLN A 263 -8. .162 35. .551 32. .330 1. .00 0. .00 XXXX1934

ATOM 1935 CA GLN A 263 -6. .753 35. .187 32. .251 1. .00 0. .00 XXXX1935

ATOM 1936 C GLN A 263 -6. .594 33. .912 31. .428 1. .00 0. .00 XXXX1936

ATOM 1937 O GLN A 263 -5. .565 33. .694 30. .790 1. .00 0. .00 XXXX1937

ATOM 1938 CB GLN A 263 -6. .152 34. .992 33. .645 1. .00 0. .00 XXXX1938

ATOM 1939 CG GLN A 263 -4. .707 34. .511 33. .622 1. .00 0. .00 XXXX1939

ATOM 1940 CD GLN A 263 -4. .144 34. .256 35. .008 1. .00 0. .00 XXXX1940

ATOM 1941 OE1 GLN A 263 -4. .574 34. .864 35. .988 1. .00 0. .00 XXXX1941

ATOM 1942 NE2 GLN A 263 -3. .173 33. .354 35. .094 1. .00 0. .00 XXXX1942

ATOM 1943 N SER A 264 -7. .630 33. .080 31. .449 1. .00 0. .00 XXXX1943

ATOM 1944 CA SER A 264 -7. .604 31. .772 30. .801 1. .00 0. .00 XXXX1944

ATOM 1945 C SER A 264 -7. .875 31. .813 29. .295 1. .00 0. .00 XXXX1945

ATOM 1946 O SER A 264 -7. .899 30. .768 28. .643 1. .00 0. .00 XXXX1946

ATOM 1947 CB SER A 264 -8. .619 30. .844 31. .469 1. .00 0. .00 XXXX1947

ATOM 1948 OG SER A 264 -9. .926 31. .392 31. .399 1. .00 0. .00 XXXX1948

ATOM 1949 N VAL A 265 -8. .084 33. .005 28. .745 1. .00 0. .00 XXXX1949

ATOM 1950 CA VAL A 265 -8. .370 33. .136 27. .317 1. .00 0. .00 XXXX1950

ATOM 1951 C VAL A 265 -7. .201 32. .625 26. .480 1. .00 0. .00 XXXX1951

ATOM 1952 O VAL A 265 -6. .054 33. .014 26. .697 1. .00 0. .00 XXXX1952

ATOM 1953 CB VAL A 265 -8. .679 34. .593 26. .927 1. .00 0. .00 XXXX1953

ATOM 1954 CGI VAL A 265 -8. .560 34. .772 25. .418 1. .00 0. .00 XXXX1954

ATOM 1955 CG2 VAL A 265 -10. .069 34. .987 27. .411 1. .00 0. .00 XXXX1955

ATOM 1956 N ASP A 266 -7. .501 31. .755 25. .521 1. .00 0. .00 XXXX1956

ATOM 1957 CA ASP A 266 -6. .461 31. .108 24. .728 1. .00 0. .00 XXXX1957

ATOM 1958 C ASP A 266 -6. .190 31. .840 23. .420 1. .00 0. .00 XXXX1958

ATOM 1959 O ASP A 266 -6. .745 31. .499 22. .375 1. .00 0. .00 XXXX1959

ATOM 1960 CB ASP A 266 -6. .841 29. .653 24. .441 1. .00 0. .00 XXXX1960

ATOM 1961 CG ASP A 266 -5. .750 28. .901 23. .699 1. .00 0. .00 XXXX1961

ATOM 1962 OD1 ASP A 266 -4. .566 29. .272 23. .839 1. .00 0. .00 XXXX1962

ATOM 1963 OD2 ASP A 266 -6. .078 27. .933 22. .980 1. .00 0. .00 XXXX1963

ATOM 1964 N THR A 267 -5. .332 32. .851 23. .490 1. .00 0. .00 XXXX1964

ATOM 1965 CA THR A 267 -4. .823 33. .523 22. .302 1. .00 0. .00 XXXX1965

ATOM 1966 C THR A 267 -3. .313 33. .674 22. .426 1. .00 0. .00 XXXX1966

ATOM 1967 O THR A 267 -2. .782 33. .667 23. .537 1. .00 0. .00 XXXX1967

ATOM 1968 CB THR A 267 -5. .463 34. .911 22. .104 1. .00 0. .00 XXXX1968

ATOM 1969 OG1 THR A 267 -5. .152 35. .748 23. .225 1. .00 0. .00 XXXX1969

ATOM 1970 CG2 THR A 267 -6. .975 34. .795 21. .970 1. .00 0. .00 XXXX1970

ATOM 1971 N PRO A 268 -2. .614 33. .805 21. .288 1. .00 0. .00 XXXX1971

ATOM 1972 CA PRO A 268 -1. .172 34. .070 21. .324 1. .00 0. .00 XXXX1972

ATOM 1973 C PRO A 268 -0. .868 35. .364 22. .075 1. .00 0. .00 XXXX1973

ATOM 1974 O PRO A 268 0. .076 35. .414 22. .863 1. .00 0. .00 XXXX1974

ATOM 1975 CB PRO A 268 -0. .796 34. .190 19. .843 1. .00 0. .00 XXXX1975

ATOM 1976 CG PRO A 268 -1. .875 33. .459 19. .111 1. .00 0. .00 XXXX1976

ATOM 1977 CD PRO A 268 -3. .123 33. .684 19. .912 1. .00 0. .00 XXXX1977

ATOM 1978 N GLU A 269 -1. .673 36. .395 21. .831 1. .00 0. .00 XXXX1978 Attorney Docket No. 35327-522001 WO

ATOM 1979 CA GLU A 269 -1. .515 37. .676 22. .509 1. .00 0. .00 XXXX1979

ATOM 1980 C GLU A 269 -1. .639 37. .542 24. .026 1. .00 0. .00 XXXX1980

ATOM 1981 O GLU A 269 -0. .836 38. .103 24. .772 1. .00 0. .00 XXXX1981

ATOM 1982 CB GLU A 269 -2. .540 38. .692 21. .994 1. .00 0. .00 XXXX1982

ATOM 1983 CG GLU A 269 -2. .181 39. .335 20. .661 1. .00 0. .00 XXXX1983

ATOM 1984 CD GLU A 269 -2. .470 38. .440 19. .470 1. .00 0. .00 XXXX1984

ATOM 1985 OE1 GLU A 269 -3. .228 37. .460 19. .626 1. .00 0. .00 XXXX1985

ATOM 1986 OE2 GLU A 269 -1. .939 38. .723 18. .376 1. .00 0. .00 XXXX1986

ATOM 1987 N ASN A 270 -2. .639 36. .794 24. .484 1. .00 0. .00 XXXX1987

ATOM 1988 CA ASN A 270 -2. .866 36. .652 25. .918 1. .00 0. .00 XXXX1988

ATOM 1989 C ASN A 270 -1. .784 35. .830 26. .606 1. .00 0. .00 XXXX1989

ATOM 1990 O ASN A 270 -1. .416 36. .110 27. .748 1. .00 0. .00 XXXX1990

ATOM 1991 CB ASN A 270 -4. .229 36. .024 26. .194 1. .00 0. .00 XXXX1991

ATOM 1992 CG ASN A 270 -4. .603 36. .095 27. .658 1. .00 0. .00 XXXX1992

ATOM 1993 OD1 ASN A 270 -4. .250 37. .052 28. .349 1. .00 0. .00 XXXX1993

ATOM 1994 ND2 ASN A 270 -5. .303 35. .078 28. .145 1. .00 0. .00 XXXX1994

ATOM 1995 N LYS A 271 -1. .289 34. .807 25. .916 1. .00 0. .00 XXXX1995

ATOM 1996 CA LYS A 271 -0. .185 34. .008 26. .432 1. .00 0. .00 XXXX1996

ATOM 1997 C LYS A 271 0. .997 34. .919 26. .751 1. .00 0. .00 XXXX1997

ATOM 1998 O LYS A 271 1. .606 34. .814 27. .816 1. .00 0. .00 XXXX1998

ATOM 1999 CB LYS A 271 0. .220 32. .923 25. .431 1. .00 0. .00 XXXX1999

ATOM 2000 CG LYS A 271 1. .313 31. .993 25. .936 1. .00 0. .00 XXXX2000

ATOM 2001 CD LYS A 271 1. .626 30. .897 24. .928 1. .00 0. .00 XXXX2001

ATOM 2002 CE LYS A 271 2. .858 30. .102 25. .337 1. .00 0. .00 XXXX2002

ATOM 2003 NZ LYS A 271 2. .655 29. .391 26. .631 1. .00 0. .00 XXXX2003

ATOM 2004 N GLU A 272 1. .309 35. .812 25. .816 1. .00 0. .00 XXXX2004

ATOM 2005 CA GLU A 272 2. .380 36. .789 25. .995 1. .00 0. .00 XXXX2005

ATOM 2006 C GLU A 272 2. .092 37. .763 27. .136 1. .00 0. .00 XXXX2006

ATOM 2007 O GLU A 272 2. .968 38. .062 27. .946 1. .00 0. .00 XXXX2007

ATOM 2008 CB GLU A 272 2. .602 37. .572 24. .698 1. .00 0. .00 XXXX2008

ATOM 2009 CG GLU A 272 3. .214 36. .759 23. .574 1. .00 0. .00 XXXX2009

ATOM 2010 CD GLU A 272 4. .559 36. .178 23. .952 1. .00 0. .00 XXXX2010

ATOM 2011 OE1 GLU A 272 5. .321 36. .864 24. .666 1. .00 0. .00 XXXX2011

ATOM 2012 OE2 GLU A 272 4. .856 35. .040 23. .533 1. .00 0. .00 XXXX2012

ATOM 2013 N PHE A 273 0. .858 38. .254 27. .189 1. .00 0. .00 XXXX2013

ATOM 2014 CA PHE A 273 0. .460 39. .240 28. .188 1. .00 0. .00 XXXX2014

ATOM 2015 C PHE A 273 0. .575 38. .681 29. .603 1. .00 0. .00 XXXX2015

ATOM 2016 O PHE A 273 1. .145 39. .320 30. .488 1. .00 0. .00 XXXX2016

ATOM 2017 CB PHE A 273 -0. .969 39. .722 27. .917 1. .00 0. .00 XXXX2017

ATOM 2018 CG PHE A 273 -1. .494 40. .690 28. .942 1. .00 0. .00 XXXX2018

ATOM 2019 CD1 PHE A 273 -0. .838 41. .885 29. .190 1. .00 0. .00 XXXX2019

ATOM 2020 CD2 PHE A 273 -2. .660 40. .416 29. .638 1. .00 0. .00 XXXX2020

ATOM 2021 CE1 PHE A 273 -1. .323 42. .779 30. .127 1. .00 0. .00 XXXX2021

ATOM 2022 CE2 PHE A 273 -3. .152 41. .308 30. .575 1. .00 0. .00 XXXX2022

ATOM 2023 CZ PHE A 273 -2. .483 42. .490 30. .819 1. .00 0. .00 XXXX2023

ATOM 2024 N VAL A 274 0. .033 37. .485 29. .811 1. .00 0. .00 XXXX2024

ATOM 2025 CA VAL A 274 0. .074 36. .845 31. .120 1. .00 0. .00 XXXX2025

ATOM 2026 C VAL A 274 1. .504 36. .505 31. .538 1. .00 0. .00 XXXX2026

ATOM 2027 O VAL A 274 1. .879 36. .692 32. .697 1. .00 0. .00 XXXX2027

ATOM 2028 CB VAL A 274 -0. .774 35. .561 31. .146 1. .00 0. .00 XXXX2028

ATOM 2029 CGI VAL A 274 -0. .595 34. .839 32. .472 1. .00 0. .00 XXXX2029

ATOM 2030 CG2 VAL A 274 -2. .244 35. .890 30. .902 1. .00 0. .00 XXXX2030

ATOM 2031 N GLU A 275 2. .299 36. .001 30. .597 1. .00 0. .00 XXXX2031

ATOM 2032 CA GLU A 275 3. .704 35. .708 30. .873 1. .00 0. .00 XXXX2032

ATOM 2033 C GLU A 275 4. .469 36. .962 31. .290 1. .00 0. .00 XXXX2033

ATOM 2034 O GLU A 275 5. .218 36. .946 32. .267 1. .00 0. .00 XXXX2034

ATOM 2035 CB GLU A 275 4. .376 35. .066 29. .656 1. .00 0. .00 XXXX2035

ATOM 2036 CG GLU A 275 4. .097 33. .580 29. .506 1. .00 0. .00 XXXX2036

ATOM 2037 CD GLU A 275 4. .967 32. .926 28. .449 1. .00 0. .00 XXXX2037

ATOM 2038 OE1 GLU A 275 6. .034 33. .488 28. .123 1. .00 0. .00 XXXX2038

ATOM 2039 OE2 GLU A 275 4. .586 31. .846 27. .951 1. .00 0. .00 XXXX2039

ATOM 2040 N LYS A 276 4. .285 38. .046 30. .544 1. .00 0. .00 XXXX2040

ATOM 2041 CA LYS A 276 4. .964 39. .301 30. .852 1. .00 0. .00 XXXX2041

ATOM 2042 C LYS A 276 4. .487 39. .898 32. .177 1. .00 0. .00 XXXX2042

ATOM 2043 O LYS A 276 5. .288 40. .420 32. .953 1. .00 0. .00 XXXX2043

ATOM 2044 CB LYS A 276 4. .776 40. .303 29. .711 1. .00 0. .00 XXXX2044

ATOM 2045 CG LYS A 276 5. .657 40. .011 28. .505 1. .00 0. .00 XXXX2045 Attorney Docket No. 35327-522001 WO

ATOM 2046 CD LYS A 276 5. .599 41. .121 27. .468 1. .00 0. .00 XXXX2046

ATOM 2047 CE LYS A 276 4. .230 41. .193 26. .813 1. .00 0. .00 XXXX2047

ATOM 2048 NZ LYS A 276 4. .197 42. .191 25. .708 1. .00 0. .00 XXXX2048

ATOM 2049 N TYR A 277 3. .183 39. .837 32. .429 1. .00 0. .00 XXXX2049

ATOM 2050 CA TYR A 277 2. .632 40. .354 33. .678 1. .00 0. .00 XXXX2050

ATOM 2051 C TYR A 277 3. .215 39. .601 34. .871 1. .00 0. .00 XXXX2051

ATOM 2052 O TYR A 277 3. .577 40. .204 35. .882 1. .00 0. .00 XXXX2052

ATOM 2053 CB TYR A 277 1. .106 40. .250 33. .678 1. .00 0. .00 XXXX2053

ATOM 2054 CG TYR A 277 0. .426 41. .081 34. .745 1. .00 0. .00 XXXX2054

ATOM 2055 CD1 TYR A 277 0. .172 42. .432 34. .544 1. .00 0. .00 XXXX2055

ATOM 2056 CD2 TYR A 277 0. .030 40. .512 35. .949 1. .00 0. .00 XXXX2056

ATOM 2057 CE1 TYR A 277 -0. .454 43. .194 35. .513 1. .00 0. .00 XXXX2057

ATOM 2058 CE2 TYR A 277 -0. .597 41. .266 36. .924 1. .00 0. .00 XXXX2058

ATOM 2059 CZ TYR A 277 -0. .837 42. .608 36. .700 1. .00 0. .00 XXXX2059

ATOM 2060 OH TYR A 277 -1. .461 43. .366 37. .666 1. .00 0. .00 XXXX2060

ATOM 2061 N LYS A 278 3. .308 38. .281 34. .743 1. .00 0. .00 XXXX2061

ATOM 2062 CA LYS A 278 3. .843 37. .441 35. .808 1. .00 0. .00 XXXX2062

ATOM 2063 C LYS A 278 5. .354 37. .608 35. .952 1. .00 0. .00 XXXX2063

ATOM 2064 O LYS A 278 5. .885 37. .583 37. .063 1. .00 0. .00 XXXX2064

ATOM 2065 CB LYS A 278 3. .502 35. .969 35. .558 1. .00 0. .00 XXXX2065

ATOM 2066 CG LYS A 278 2. .040 35. .613 35. .807 1. .00 0. .00 XXXX2066

ATOM 2067 CD LYS A 278 1. .762 34. .157 35. .458 1. .00 0. .00 XXXX2067

ATOM 2068 CE LYS A 278 0. .327 33. .770 35. .774 1. .00 0. .00 XXXX2068

ATOM 2069 NZ LYS A 278 0. .072 33. .737 37. .242 1. .00 0. .00 XXXX2069

ATOM 2070 N LYS A 279 6. .045 37. .774 34. .828 1. .00 0. .00 XXXX2070

ATOM 2071 CA LYS A 279 7. .487 37. .996 34. .853 1. .00 0. .00 XXXX2071

ATOM 2072 C LYS A 279 7. .846 39. .264 35. .623 1. .00 0. .00 XXXX2072

ATOM 2073 O LYS A 279 8. .836 39. .297 36. .354 1. .00 0. .00 XXXX2073

ATOM 2074 CB LYS A 279 8. .048 38. .077 33. .432 1. .00 0. .00 XXXX2074

ATOM 2075 CG LYS A 279 9. .542 38. .363 33. .389 1. .00 0. .00 XXXX2075

ATOM 2076 CD LYS A 279 10. .077 38. .403 31. .966 1. .00 0. .00 XXXX2076

ATOM 2077 CE LYS A 279 11. .551 38. .787 31. .947 1. .00 0. .00 XXXX2077

ATOM 2078 NZ LYS A 279 12. .132 38. .730 30. .576 1. .00 0. .00 XXXX2078

ATOM 2079 N LYS A 280 7. .039 40. .307 35. .456 1. .00 0. .00 XXXX2079

ATOM 2080 CA LYS A 280 7. .305 41. .581 36. .114 1. .00 0. .00 XXXX2080

ATOM 2081 C LYS A 280 6. .900 41. .585 37. .585 1. .00 0. .00 XXXX2081

ATOM 2082 O LYS A 280 7. .633 42. .097 38. .430 1. .00 0. .00 XXXX2082

ATOM 2083 CB LYS A 280 6. .589 42. .723 35. .386 1. .00 0. .00 XXXX2083

ATOM 2084 CG LYS A 280 6. .938 44. .101 35. .936 1. .00 0. .00 XXXX2084

ATOM 2085 CD LYS A 280 6. .360 45. .215 35. .082 1. .00 0. .00 XXXX2085

ATOM 2086 CE LYS A 280 6. .717 46. .582 35. .648 1. .00 0. .00 XXXX2086

ATOM 2087 NZ LYS A 280 8. .186 46. .743 35. .838 1. .00 0. .00 XXXX2087

ATOM 2088 N TYR A 281 5. .736 41. .020 37. .891 1. .00 0. .00 XXXX2088

ATOM 2089 CA TYR A 281 5. .166 41. .156 39. .229 1. .00 0. .00 XXXX2089

ATOM 2090 C TYR A 281 5. .142 39. .862 40. .046 1. .00 0. .00 XXXX2090

ATOM 2091 O TYR A 281 4. .853 39. .890 41. .242 1. .00 0. .00 XXXX2091

ATOM 2092 CB TYR A 281 3. .749 41. .725 39. .126 1. .00 0. .00 XXXX2092

ATOM 2093 CG TYR A 281 3. .717 43. .116 38. .538 1. .00 0. .00 XXXX2093

ATOM 2094 CD1 TYR A 281 4. .353 44. .172 39. .176 1. .00 0. .00 XXXX2094

ATOM 2095 CD2 TYR A 281 3. .057 43. .373 37. .343 1. .00 0. .00 XXXX2095

ATOM 2096 CE1 TYR A 281 4. .334 45. .444 38. .644 1. .00 0. .00 XXXX2096

ATOM 2097 CE2 TYR A 281 3. .030 44. .644 36. .802 1. .00 0. .00 XXXX2097

ATOM 2098 CZ TYR A 281 3. .671 45. .676 37. .457 1. .00 0. .00 XXXX2098

ATOM 2099 OH TYR A 281 3. .648 46. .943 36. .923 1. .00 0. .00 XXXX2099

ATOM 2100 N GLY A 282 5. .444 38. .734 39. .410 1. .00 0. .00 XXXX2100

ATOM 2101 CA GLY A 282 5. .496 37. .468 40. .121 1. .00 0. .00 XXXX2101

ATOM 2102 C GLY A 282 4. .573 36. .411 39. .545 1. .00 0. .00 XXXX2102

ATOM 2103 O GLY A 282 3. .477 36. .719 39. .077 1. .00 0. .00 XXXX2103

ATOM 2104 N GLU A 283 5. .018 35. .158 39. .586 1. .00 0. .00 XXXX2104

ATOM 2105 CA GLU A 283 4. .272 34. .051 38. .993 1. .00 0. .00 XXXX2105

ATOM 2106 C GLU A 283 2. .931 33. .791 39. .675 1. .00 0. .00 XXXX2106

ATOM 2107 O GLU A 283 2. .069 33. .112 39. .119 1. .00 0. .00 XXXX2107

ATOM 2108 CB GLU A 283 5. .114 32. .774 39. .021 1. .00 0. .00 XXXX2108

ATOM 2109 CG GLU A 283 6. .187 32. .717 37. .949 1. .00 0. .00 XXXX2109

ATOM 2110 CD GLU A 283 5. .615 32. .829 36. .549 1. .00 0. .00 XXXX2110

ATOM 2111 OE1 GLU A 283 4. .609 32. .146 36. .261 1. .00 0. .00 XXXX2111

ATOM 2112 OE2 GLU A 283 6. .172 33. .598 35. .736 1. .00 0. .00 XXXX2112 Attorney Docket No. 35327-522001 WO

ATOM 2113 N ASP A 284 2. .754 34. .331 40. .876 1. .00 0. .00 XXXX2113

ATOM 2114 CA ASP A 284 1. .508 34. .143 41. .613 1. .00 0. .00 XXXX2114

ATOM 2115 C ASP A 284 0. .439 35. .143 41. .185 1. .00 0. .00 XXXX2115

ATOM 2116 O ASP A 284 -0. .746 34. .950 41. .455 1. .00 0. .00 XXXX2116

ATOM 2117 CB ASP A 284 1. .751 34. .255 43. .119 1. .00 0. .00 XXXX2117

ATOM 2118 CG ASP A 284 2. .195 32. .943 43. .737 1. .00 0. .00 XXXX2118

ATOM 2119 OD1 ASP A 284 2. .534 32. .010 42. .978 1. .00 0. .00 XXXX2119

ATOM 2120 OD2 ASP A 284 2. .197 32. .843 44. .982 1. .00 0. .00 XXXX2120

ATOM 2121 N ARG A 285 0. .862 36. .209 40. .515 1. .00 0. .00 XXXX2121

ATOM 2122 CA ARG A 285 -0. .059 37. .267 40. .120 1. .00 0. .00 XXXX2122

ATOM 2123 C ARG A 285 -1. .003 36. .807 39. .013 1. .00 0. .00 XXXX2123

ATOM 2124 O ARG A 285 -0. .619 36. .044 38. .127 1. .00 0. .00 XXXX2124

ATOM 2125 CB ARG A 285 0. .714 38. .508 39. .669 1. .00 0. .00 XXXX2125

ATOM 2126 CG ARG A 285 1. .504 39. .178 40. .782 1. .00 0. .00 XXXX2126

ATOM 2127 CD ARG A 285 0. .582 39. .864 41. .781 1. .00 0. .00 XXXX2127

ATOM 2128 NE ARG A 285 -0. .167 40. .962 41. .177 1. .00 0. .00 XXXX2128

ATOM 2129 CZ ARG A 285 0. .248 42. .225 41. .157 1. .00 0. .00 XXXX2129

ATOM 2130 NH1 ARG A 285 1. .410 42. .548 41. .707 1. .00 0. .00 XXXX2130

ATOM 2131 NH2 ARG A 285 -0. .496 43. .163 40. .587 1. .00 0. .00 XXXX2131

ATOM 2132 N VAL A 286 -2. .244 37. .276 39. .075 1. .00 0. .00 XXXX2132

ATOM 2133 CA VAL A 286 -3. .235 36. .949 38. .062 1. .00 0. .00 XXXX2133

ATOM 2134 C VAL A 286 -3. .527 38. .165 37. .196 1. .00 0. .00 XXXX2134

ATOM 2135 O VAL A 286 -3. .177 39. .290 37. .554 1. .00 0. .00 XXXX2135

ATOM 2136 CB VAL A 286 -4. .549 36. .458 38. .688 1. .00 0. .00 XXXX2136

ATOM 2137 CGI VAL A 286 -4. .311 35. .197 39. .502 1. .00 0. .00 XXXX2137

ATOM 2138 CG2 VAL A 286 -5. .156 37. .549 39. .556 1. .00 0. .00 XXXX2138

ATOM 2139 N THR A 287 -4. .158 37. .931 36. .052 1. .00 0. .00 XXXX2139

ATOM 2140 CA THR A 287 -4. .687 39. .015 35. .238 1. .00 0. .00 XXXX2140

ATOM 2141 C THR A 287 -6. .204 38. .896 35. .183 1. .00 0. .00 XXXX2141

ATOM 2142 O THR A 287 -6. .759 37. .839 35. .481 1. .00 0. .00 XXXX2142

ATOM 2143 CB THR A 287 -4. .112 39. .005 33. .809 1. .00 0. .00 XXXX2143

ATOM 2144 OG1 THR A 287 -4. .490 37. .795 33. .141 1. .00 0. .00 XXXX2144

ATOM 2145 CG2 THR A 287 -2. .593 39. .112 33. .841 1. .00 0. .00 XXXX2145

ATOM 2146 N ASP A 288 -6. .872 39. .980 34. .806 1. .00 0. .00 XXXX2146

ATOM 2147 CA ASP A 288 -8. .315 39. .945 34. .606 1. .00 0. .00 XXXX2147

ATOM 2148 C ASP A 288 -8. .759 41. .070 33. .676 1. .00 0. .00 XXXX2148

ATOM 2149 O ASP A 288 -7. .928 41. .809 33. .147 1. .00 0. .00 XXXX2149

ATOM 2150 CB ASP A 288 -9. .061 40. .004 35. .951 1. .00 0. .00 XXXX2150

ATOM 2151 CG ASP A 288 -8. .820 41. .297 36. .725 1. .00 0. .00 XXXX2151

ATOM 2152 OD1 ASP A 288 -8. .356 42. .297 36. .143 1. .00 0. .00 XXXX2152

ATOM 2153 OD2 ASP A 288 -9. .115 41. .313 37. .940 1. .00 0. .00 XXXX2153

ATOM 2154 N ASP A 289 -10. .068 41. .191 33. .482 1. .00 0. .00 XXXX2154

ATOM 2155 CA ASP A 289 -10. .622 42. .096 32. .480 1. .00 0. .00 XXXX2155

ATOM 2156 C ASP A 289 -10. .182 43. .547 32. .698 1. .00 0. .00 XXXX2156

ATOM 2157 O ASP A 289 -9. .627 44. .168 31. .790 1. .00 0. .00 XXXX2157

ATOM 2158 CB ASP A 289 -12. .151 41. .995 32. .475 1. .00 0. .00 XXXX2158

ATOM 2159 CG ASP A 289 -12. .798 42. .893 31. .439 1. .00 0. .00 XXXX2159

ATOM 2160 OD1 ASP A 289 -12. .792 44. .129 31. .622 1. .00 0. .00 XXXX2160

ATOM 2161 OD2 ASP A 289 -13. .328 42. .357 30. .444 1. .00 0. .00 XXXX2161

ATOM 2162 N PRO A 290 -10. .432 44. .093 33. .902 1. .00 0. .00 XXXX2162

ATOM 2163 CA PRO A 290 -10. .006 45. .463 34. .210 1. .00 0. .00 XXXX2163

ATOM 2164 C PRO A 290 -8. .502 45. .654 34. .033 1. .00 0. .00 XXXX2164

ATOM 2165 O PRO A 290 -8. .070 46. .699 33. .551 1. .00 0. .00 XXXX2165

ATOM 2166 CB PRO A 290 -10. .410 45. .634 35. .676 1. .00 0. .00 XXXX2166

ATOM 2167 CG PRO A 290 -11. .551 44. .695 35. .855 1. .00 0. .00 XXXX2167

ATOM 2168 CD PRO A 290 -11. .219 43. .505 35. .000 1. .00 0. .00 XXXX2168

ATOM 2169 N ILE A 291 -7. .720 44. .652 34. .421 1. .00 0. .00 XXXX2169

ATOM 2170 CA ILE A 291 -6. .272 44. .705 34. .245 1. .00 0. .00 XXXX2170

ATOM 2171 C ILE A 291 -5. .891 44. .784 32. .766 1. .00 0. .00 XXXX2171

ATOM 2172 O ILE A 291 -4. .987 45. .533 32. .390 1. .00 0. .00 XXXX2172

ATOM 2173 CB ILE A 291 -5. .585 43. .491 34. .892 1. .00 0. .00 XXXX2173

ATOM 2174 CGI ILE A 291 -5. .588 43. .633 36. .416 1. .00 0. .00 XXXX2174

ATOM 2175 CG2 ILE A 291 -4. .161 43. .352 34. .384 1. .00 0. .00 XXXX2175

ATOM 2176 CD1 ILE A 291 -5. .166 42. .375 37. .147 1. .00 0. .00 XXXX2176

ATOM 2177 N GLU A 292 -6. .578 44. .013 31. .927 1. .00 0. .00 XXXX2177

ATOM 2178 CA GLU A 292 -6. .331 44. .066 30. .491 1. .00 0. .00 XXXX2178

ATOM 2179 C GLU A 292 -6. .712 45. .427 29. .920 1. .00 0. .00 XXXX2179 Attorney Docket No. 35327-522001 WO

ATOM 2180 O GLU A 292 -5. .988 45. .988 29. .097 1. .00 0. .00 XXXX2180

ATOM 2181 CB GLU A 292 -7. .102 42. .969 29. .753 1. .00 0. .00 XXXX2181

ATOM 2182 CG GLU A 292 -6. .723 42. .871 28. .279 1. .00 0. .00 XXXX2182

ATOM 2183 CD GLU A 292 -7. .890 42. .497 27. .385 1. .00 0. .00 XXXX2183

ATOM 2184 OE1 GLU A 292 -7. .644 42. .092 26. .229 1. .00 0. .00 XXXX2184

ATOM 2185 OE2 GLU A 292 -9. .052 42. .621 27. .828 1. .00 0. .00 XXXX2185

ATOM 2186 N ALA A 293 -7. .853 45. .949 30. .362 1. .00 0. .00 XXXX2186

ATOM 2187 CA ALA A 293 -8. .370 47. .220 29. .863 1. .00 0. .00 XXXX2187

ATOM 2188 C ALA A 293 -7. .426 48. .367 30. .200 1. .00 0. .00 XXXX2188

ATOM 2189 O ALA A 293 -7. .218 49. .270 29. .390 1. .00 0. .00 XXXX2189

ATOM 2190 CB ALA A 293 -9. .760 47. .491 30. .434 1. .00 0. .00 XXXX2190

ATOM 2191 N ALA A 294 -6. .858 48. .328 31. .400 1. .00 0. .00 XXXX2191

ATOM 2192 CA ALA A 294 -5. .907 49. .348 31. .826 1. .00 0. .00 XXXX2192

ATOM 2193 C ALA A 294 -4. .660 49. .290 30. .951 1. .00 0. .00 XXXX2193

ATOM 2194 O ALA A 294 -4. .137 50. .317 30. .519 1. .00 0. .00 XXXX2194

ATOM 2195 CB ALA A 294 -5. .545 49. .163 33. .290 1. .00 0. .00 XXXX2195

ATOM 2196 N TYR A 295 -4. .194 48. .071 30. .703 1. .00 0. .00 XXXX2196

ATOM 2197 CA TYR A 295 -3. .043 47. .819 29. .844 1. .00 0. .00 XXXX2197

ATOM 2198 C TYR A 295 -3. .330 48. .287 28. .416 1. .00 0. .00 XXXX2198

ATOM 2199 O TYR A 295 -2. .535 49. .013 27. .815 1. .00 0. .00 XXXX2199

ATOM 2200 CB TYR A 295 -2. .695 46. .327 29. .879 1. .00 0. .00 XXXX2200

ATOM 2201 CG TYR A 295 -1. .568 45. .897 28. .968 1. .00 0. .00 XXXX2201

ATOM 2202 CD1 TYR A 295 -1. .829 45. .325 27. .730 1. .00 0. .00 XXXX2202

ATOM 2203 CD2 TYR A 295 -0. .244 46. .036 29. .360 1. .00 0. .00 XXXX2203

ATOM 2204 CE1 TYR A 295 -0. .800 44. .918 26. .900 1. .00 0. .00 XXXX2204

ATOM 2205 CE2 TYR A 295 0. .791 45. .632 28. .537 1. .00 0. .00 XXXX2205

ATOM 2206 CZ TYR A 295 0. .508 45. .074 27. .308 1. .00 0. .00 XXXX2206

ATOM 2207 OH TYR A 295 1. .539 44. .672 26. .488 1. .00 0. .00 XXXX2207

ATOM 2208 N ILE A 296 -4. .471 47. .862 27. .882 1. .00 0. .00 XXXX2208

ATOM 2209 CA ILE A 296 -4. .932 48. .283 26. .560 1. .00 0. .00 XXXX2209

ATOM 2210 C ILE A 296 -5. .033 49. .800 26. .414 1. .00 0. .00 XXXX2210

ATOM 2211 O ILE A 296 -4. .621 50. .362 25. .399 1. .00 0. .00 XXXX2211

ATOM 2212 CB ILE A 296 -6. .313 47. .679 26. .235 1. .00 0. .00 XXXX2212

ATOM 2213 CGI ILE A 296 -6. .176 46. .217 25. .809 1. .00 0. .00 XXXX2213

ATOM 2214 CG2 ILE A 296 -7. .013 48. .492 25. .154 1. .00 0. .00 XXXX2214

ATOM 2215 CD1 ILE A 296 -7. .498 45. .567 25. .476 1. .00 0. .00 XXXX2215

ATOM 2216 N GLY A 297 -5. .591 50. .454 27. .429 1. .00 0. .00 XXXX2216

ATOM 2217 CA GLY A 297 -5. .815 51. .888 27. .396 1. .00 0. .00 XXXX2217

ATOM 2218 C GLY A 297 -4. .565 52. .712 27. .149 1. .00 0. .00 XXXX2218

ATOM 2219 O GLY A 297 -4. .590 53. .678 26. .387 1. .00 0. .00 XXXX2219

ATOM 2220 N VAL A 298 -3. .469 52. .334 27. .799 1. .00 0. .00 XXXX2220

ATOM 2221 CA VAL A 298 -2. .203 53. .033 27. .619 1. .00 0. .00 XXXX2221

ATOM 2222 C VAL A 298 -1. .717 52. .907 26. .180 1. .00 0. .00 XXXX2222

ATOM 2223 O VAL A 298 -1. .292 53. .889 25. .571 1. .00 0. .00 XXXX2223

ATOM 2224 CB VAL A 298 -1. .119 52. .498 28. .571 1. .00 0. .00 XXXX2224

ATOM 2225 CGI VAL A 298 0. .225 53. .152 28. .269 1. .00 0. .00 XXXX2225

ATOM 2226 CG2 VAL A 298 -1. .523 52. .734 30. .019 1. .00 0. .00 XXXX2226

ATOM 2227 N TYR A 299 -1. .787 51. .694 25. .640 1. .00 0. .00 XXXX2227

ATOM 2228 CA TYR A 299 -1. .354 51. .445 24. .269 1. .00 0. .00 XXXX2228

ATOM 2229 C TYR A 299 -2. .208 52. .186 23. .247 1. .00 0. .00 XXXX2229

ATOM 2230 O TYR A 299 -1. .685 52. .720 22. .270 1. .00 0. .00 XXXX2230

ATOM 2231 CB TYR A 299 -1. .365 49. .945 23. .967 1. .00 0. .00 XXXX2231

ATOM 2232 CG TYR A 299 -0. .039 49. .270 24. .231 1. .00 0. .00 XXXX2232

ATOM 2233 CD1 TYR A 299 0. .978 49. .312 23. .286 1. .00 0. .00 XXXX2233

ATOM 2234 CD2 TYR A 299 0. .203 48. .604 25. .425 1. .00 0. .00 XXXX2234

ATOM 2235 CE1 TYR A 299 2. .195 48. .704 23. .518 1. .00 0. .00 XXXX2235

ATOM 2236 CE2 TYR A 299 1. .421 47. .992 25. .666 1. .00 0. .00 XXXX2236

ATOM 2237 CZ TYR A 299 2. .413 48. .046 24. .708 1. .00 0. .00 XXXX2237

ATOM 2238 OH TYR A 299 3. .629 47. .442 24. .935 1. .00 0. .00 XXXX2238

ATOM 2239 N LEU A 300 -3. .517 52. .223 23. .472 1. .00 0. .00 XXXX2239

ATOM 2240 CA LEU A 300 -4. .415 52. .883 22. .532 1. .00 0. .00 XXXX2240

ATOM 2241 C LEU A 300 -4. .236 54. .398 22. .557 1. .00 0. .00 XXXX2241

ATOM 2242 O LEU A 300 -4. .266 55. .042 21. .509 1. .00 0. .00 XXXX2242

ATOM 2243 CB LEU A 300 -5. .871 52. .506 22. .813 1. .00 0. .00 XXXX2243

ATOM 2244 CG LEU A 300 -6. .257 51. .135 22. .248 1. .00 0. .00 XXXX2244

ATOM 2245 CD1 LEU A 300 -7. .653 50. .723 22. .688 1. .00 0. .00 XXXX2245

ATOM 2246 CD2 LEU A 300 -6. .145 51. .131 20. .726 1. .00 0. .00 XXXX2246 Attorney Docket No. 35327-522001 WO

ATOM 2247 N TRP A 301 -4. .059 54. .968 23. .746 1. .00 0. .00 XXXX2247

ATOM 2248 CA TRP A 301 -3. .746 56. .390 23. .846 1. .00 0. .00 XXXX2248

ATOM 2249 C TRP A 301 -2. .453 56. .705 23. .108 1. .00 0. .00 XXXX2249

ATOM 2250 O TRP A 301 -2. .381 57. .667 22. .344 1. .00 0. .00 XXXX2250

ATOM 2251 CB TRP A 301 -3. .620 56. .840 25. .301 1. .00 0. .00 XXXX2251

ATOM 2252 CG TRP A 301 -3. .024 58. .216 25. .412 1. .00 0. .00 XXXX2252

ATOM 2253 CD1 TRP A 301 -3. .670 59. .405 25. .236 1. .00 0. .00 XXXX2253

ATOM 2254 CD2 TRP A 301 -1. .656 58. .542 25. .697 1. .00 0. .00 XXXX2254

ATOM 2255 NE1 TRP A 301 -2. .792 60. .450 25. .402 1. .00 0. .00 XXXX2255

ATOM 2256 CE2 TRP A 301 -1. .551 59. .947 25. .688 1. .00 0. .00 XXXX2256

ATOM 2257 CE3 TRP A 301 -0. .514 57. .782 25. .965 1. .00 0. .00 XXXX2257

ATOM 2258 CZ2 TRP A 301 -0. .348 60. .608 25. .936 1. .00 0. .00 XXXX2258

ATOM 2259 CZ3 TRP A 301 0. .679 58. .440 26. .211 1. .00 0. .00 XXXX2259

ATOM 2260 CH2 TRP A 301 0. .753 59. .839 26. .195 1. .00 0. .00 XXXX2260

ATOM 2261 N ALA A 302 -1. .432 55. .890 23. .351 1. .00 0. .00 XXXX2261

ATOM 2262 CA ALA A 302 -0. .124 56. .101 22. .744 1. .00 0. .00 XXXX2262

ATOM 2263 C ALA A 302 -0. .209 55. .996 21. .225 1. .00 0. .00 XXXX2263

ATOM 2264 O ALA A 302 0. .421 56. .773 20. .507 1. .00 0. .00 XXXX2264

ATOM 2265 CB ALA A 302 0. .886 55. .103 23. .294 1. .00 0. .00 XXXX2265

ATOM 2266 N LYS A 303 -0. .996 55. .038 20. .741 1. .00 0. .00 XXXX2266

ATOM 2267 CA LYS A 303 -1. .204 54. .871 19. .306 1. .00 0. .00 XXXX2267

ATOM 2268 C LYS A 303 -1. .929 56. .070 18. .702 1. .00 0. .00 XXXX2268

ATOM 2269 O LYS A 303 -1. .607 56. .507 17. .597 1. .00 0. .00 XXXX2269

ATOM 2270 CB LYS A 303 -1. .988 53. .587 19. .021 1. .00 0. .00 XXXX2270

ATOM 2271 CG LYS A 303 -1. .216 52. .312 19. .318 1. .00 0. .00 XXXX2271

ATOM 2272 CD LYS A 303 -1. .974 51. .087 18. .838 1. .00 0. .00 XXXX2272

ATOM 2273 CE LYS A 303 -2. .145 51. .111 17. .328 1. .00 0. .00 XXXX2273

ATOM 2274 NZ LYS A 303 -2. .680 49. .828 16. .805 1. .00 0. .00 XXXX2274

ATOM 2275 N ALA A 304 -2. .908 56. .597 19. .430 1. .00 0. .00 XXXX2275

ATOM 2276 CA ALA A 304 -3. .644 57. .772 18. .979 1. .00 0. .00 XXXX2276

ATOM 2277 C ALA A 304 -2. .720 58. .984 18. .905 1. .00 0. .00 XXXX2277

ATOM 2278 O ALA A 304 -2. .804 59. .786 17. .976 1. .00 0. .00 XXXX2278

ATOM 2279 CB ALA A 304 -4. .822 58. .053 19. .899 1. .00 0. .00 XXXX2279

ATOM 2280 N VAL A 305 -1. .837 59. .106 19. .892 1. .00 0. .00 XXXX2280

ATOM 2281 CA VAL A 305 -0. .860 60. .190 19. .922 1. .00 0. .00 XXXX2281

ATOM 2282 C VAL A 305 0. .122 60. .078 18. .760 1. .00 0. .00 XXXX2282

ATOM 2283 O VAL A 305 0. .396 61. .060 18. .068 1. .00 0. .00 XXXX2283

ATOM 2284 CB VAL A 305 -0. .073 60. .201 21. .246 1. .00 0. .00 XXXX2284

ATOM 2285 CGI VAL A 305 1. .135 61. .120 21. .141 1. .00 0. .00 XXXX2285

ATOM 2286 CG2 VAL A 305 -0. .977 60. .622 22. .395 1. .00 0. .00 XXXX2286

ATOM 2287 N GLU A 306 0. .651 58. .876 18. .555 1. .00 0. .00 XXXX2287

ATOM 2288 CA GLU A 306 1. .550 58. .605 17. .438 1. .00 0. .00 XXXX2288

ATOM 2289 C GLU A 306 0. .916 58. .965 16. .098 1. .00 0. .00 XXXX2289

ATOM 2290 O GLU A 306 1. .546 59. .599 15. .251 1. .00 0. .00 XXXX2290

ATOM 2291 CB GLU A 306 1. .973 57. .136 17. .442 1. .00 0. .00 XXXX2291

ATOM 2292 CG GLU A 306 3. .115 56. .840 18. .392 1. .00 0. .00 XXXX2292

ATOM 2293 CD GLU A 306 4. .383 57. .557 17. .986 1. .00 0. .00 XXXX2293

ATOM 2294 OE1 GLU A 306 4. .618 57. .674 16. .767 1. .00 0. .00 XXXX2294

ATOM 2295 OE2 GLU A 306 5. .135 58. .009 18. .874 1. .00 0. .00 XXXX2295

ATOM 2296 N LYS A 307 -0. .332 58. .550 15. .915 1. .00 0. .00 XXXX2296

ATOM 2297 CA LYS A 307 -1. .061 58. .813 14. .681 1. .00 0. .00 XXXX2297

ATOM 2298 C LYS A 307 -1. .351 60. .302 14. .517 1. .00 0. .00 XXXX2298

ATOM 2299 O LYS A 307 -1. .240 60. .848 13. .418 1. .00 0. .00 XXXX2299

ATOM 2300 CB LYS A 307 -2. .364 58. .012 14. .659 1. .00 0. .00 XXXX2300

ATOM 2301 CG LYS A 307 -3. .231 58. .247 13. .436 1. .00 0. .00 XXXX2301

ATOM 2302 CD LYS A 307 -4. .505 57. .423 13. .513 1. .00 0. .00 XXXX2302

ATOM 2303 CE LYS A 307 -5. .533 57. .889 12. .499 1. .00 0. .00 XXXX2303

ATOM 2304 NZ LYS A 307 -6. .840 57. .203 12. .698 1. .00 0. .00 XXXX2304

ATOM 2305 N ALA A 308 -1. .716 60. .953 15. .617 1. .00 0. .00 XXXX2305

ATOM 2306 CA ALA A 308 -2. .026 62. .378 15. .599 1. .00 0. .00 XXXX2306

ATOM 2307 C ALA A 308 -0. .774 63. .233 15. .417 1. .00 0. .00 XXXX2307

ATOM 2308 O ALA A 308 -0. .851 64. .361 14. .929 1. .00 0. .00 XXXX2308

ATOM 2309 CB ALA A 308 -2. .752 62. .775 16. .877 1. .00 0. .00 XXXX2309

ATOM 2310 N GLY A 309 0. .376 62. .697 15. .811 1. .00 0. .00 XXXX2310

ATOM 2311 CA GLY A 309 1. .614 63. .453 15. .776 1. .00 0. .00 XXXX2311

ATOM 2312 C GLY A 309 1. .640 64. .531 16. .845 1. .00 0. .00 XXXX2312

ATOM 2313 O GLY A 309 2. .423 65. .477 16. .769 1. .00 0. .00 XXXX2313 Attorney Docket No. 35327-522001 WO

ATOM 2314 N SER A 310 0. .776 64. .383 17. .844 1. .00 0. .00 XXXX2314

ATOM 2315 CA SER A 310 0. .624 65. .387 18. .889 1. .00 0. .00 XXXX2315

ATOM 2316 C SER A 310 -0. .126 64. .810 20. .083 1. .00 0. .00 XXXX2316

ATOM 2317 O SER A 310 -0. .924 63. .886 19. .936 1. .00 0. .00 XXXX2317

ATOM 2318 CB SER A 310 -0. .111 66. .616 18. .347 1. .00 0. .00 XXXX2318

ATOM 2319 OG SER A 310 -0. .331 67. .579 19. .368 1. .00 0. .00 XXXX2319

ATOM 2320 N THR A 311 0. .138 65. .356 21. .265 1. .00 0. .00 XXXX2320

ATOM 2321 CA THR A 311 -0. .593 64. .969 22. .464 1. .00 0. .00 XXXX2321

ATOM 2322 C THR A 311 -1. .816 65. .860 22. .654 1. .00 0. .00 XXXX2322

ATOM 2323 O THR A 311 -2. .598 65. .665 23. .586 1. .00 0. .00 XXXX2323

ATOM 2324 CB THR A 311 0. .294 65. .046 23. .719 1. .00 0. .00 XXXX2324

ATOM 2325 OG1 THR A 311 0. .746 66. .392 23. .905 1. .00 0. .00 XXXX2325

ATOM 2326 CG2 THR A 311 1. .496 64. .126 23. .578 1. .00 0. .00 XXXX2326

ATOM 2327 N ASP A 312 -1. .968 66. .844 21. .771 1. .00 0. .00 XXXX2327

ATOM 2328 CA ASP A 312 -3. .124 67. .736 21. .801 1. .00 0. .00 XXXX2328

ATOM 2329 C ASP A 312 -4. .421 66. .934 21. .807 1. .00 0. .00 XXXX2329

ATOM 2330 O ASP A 312 -4. .637 66. .080 20. .946 1. .00 0. .00 XXXX2330

ATOM 2331 CB ASP A 312 -3. .099 68. .697 20. .610 1. .00 0. .00 XXXX2331

ATOM 2332 CG ASP A 312 -4. .318 69. .597 20. .564 1. .00 0. .00 XXXX2332

ATOM 2333 OD1 ASP A 312 -4. .348 70. .598 21. .311 1. .00 0. .00 XXXX2333

ATOM 2334 OD2 ASP A 312 -5. .248 69. .304 19. .783 1. .00 0. .00 XXXX2334

ATOM 2335 N VAL A 313 -5. .279 67. .218 22. .783 1. .00 0. .00 XXXX2335

ATOM 2336 CA VAL A 313 -6. .462 66. .402 23. .042 1. .00 0. .00 XXXX2336

ATOM 2337 C VAL A 313 -7. .408 66. .319 21. .846 1. .00 0. .00 XXXX2337

ATOM 2338 O VAL A 313 -7. .921 65. .246 21. .530 1. .00 0. .00 XXXX2338

ATOM 2339 CB VAL A 313 -7. .247 66. .934 24. .258 1. .00 0. .00 XXXX2339

ATOM 2340 CGI VAL A 313 -8. .644 66. .332 24. .296 1. .00 0. .00 XXXX2340

ATOM 2341 CG2 VAL A 313 -6. .497 66. .627 25. .545 1. .00 0. .00 XXXX2341

ATOM 2342 N ASP A 314 -7. .642 67. .448 21. .184 1. .00 0. .00 XXXX2342

ATOM 2343 CA ASP A 314 -8. .544 67. .470 20. .036 1. .00 0. .00 XXXX2343

ATOM 2344 C ASP A 314 -8. .019 66. .622 18. .881 1. .00 0. .00 XXXX2344

ATOM 2345 O ASP A 314 -8. .789 65. .950 18. .196 1. .00 0. .00 XXXX2345

ATOM 2346 CB ASP A 314 -8. .781 68. .907 19. .565 1. .00 0. .00 XXXX2346

ATOM 2347 CG ASP A 314 -9. .575 69. .726 20. .565 1. .00 0. .00 XXXX2347

ATOM 2348 OD1 ASP A 314 -10. .291 69. .127 21. .396 1. .00 0. .00 XXXX2348

ATOM 2349 OD2 ASP A 314 -9. .491 70. .971 20. .516 1. .00 0. .00 XXXX2349

ATOM 2350 N LYS A 315 -6. .709 66. .657 18. .665 1. .00 0. .00 XXXX2350

ATOM 2351 CA LYS A 315 -6. .094 65. .859 17. .610 1. .00 0. .00 XXXX2351

ATOM 2352 C LYS A 315 -6. .078 64. .376 17. .970 1. .00 0. .00 XXXX2352

ATOM 2353 O LYS A 315 -6. .306 63. .519 17. .116 1. .00 0. .00 XXXX2353

ATOM 2354 CB LYS A 315 -4. .678 66. .356 17. .325 1. .00 0. .00 XXXX2354

ATOM 2355 CG LYS A 315 -4. .641 67. .760 16. .752 1. .00 0. .00 XXXX2355

ATOM 2356 CD LYS A 315 -3. .218 68. .258 16. .593 1. .00 0. .00 XXXX2356

ATOM 2357 CE LYS A 315 -3. .199 69. .677 16. .049 1. .00 0. .00 XXXX2357

ATOM 2358 NZ LYS A 315 -1. .816 70. .162 15. .791 1. .00 0. .00 XXXX2358

ATOM 2359 N VAL A 316 -5. .805 64. .082 19. .237 1. .00 0. .00 XXXX2359

ATOM 2360 CA VAL A 316 -5. .798 62. .706 19. .717 1. .00 0. .00 XXXX2360

ATOM 2361 C VAL A 316 -7. .189 62. .092 19. .600 1. .00 0. .00 XXXX2361

ATOM 2362 O VAL A 316 -7. .331 60. .937 19. .201 1. .00 0. .00 XXXX2362

ATOM 2363 CB VAL A 316 -5. .321 62. .613 21. .177 1. .00 0. .00 XXXX2363

ATOM 2364 CGI VAL A 316 -5. .593 61. .224 21. .735 1. .00 0. .00 XXXX2364

ATOM 2365 CG2 VAL A 316 -3. .838 62. .953 21. .274 1. .00 0. .00 XXXX2365

ATOM 2366 N ARG A 317 -8. .211 62. .866 19. .959 1. .00 0. .00 XXXX2366

ATOM 2367 CA ARG A 317 -9. .591 62. .403 19. .862 1. .00 0. .00 XXXX2367

ATOM 2368 C ARG A 317 -9. .950 62. .024 18. .429 1. .00 0. .00 XXXX2368

ATOM 2369 O ARG A 317 -10. .586 60. .997 18. .188 1. .00 0. .00 XXXX2369

ATOM 2370 CB ARG A 317 -10. .559 63. .472 20. .375 1. .00 0. .00 XXXX2370

ATOM 2371 CG ARG A 317 -12. .003 63. .000 20. .424 1. .00 0. .00 XXXX2371

ATOM 2372 CD ARG A 317 -12. .963 64. .105 20. .837 1. .00 0. .00 XXXX2372

ATOM 2373 NE ARG A 317 -12. .660 64. .645 22. .158 1. .00 0. .00 XXXX2373

ATOM 2374 CZ ARG A 317 -12. .020 65. .790 22. .369 1. .00 0. .00 XXXX2374

ATOM 2375 NH1 ARG A 317 -11. .617 66. .526 21. .344 1. .00 0. .00 XXXX2375

ATOM 2376 NH2 ARG A 317 -11. .789 66. .202 23. .608 1. .00 0. .00 XXXX2376

ATOM 2377 N GLU A 318 -9. .544 62. .862 17. .482 1. .00 0. .00 XXXX2377

ATOM 2378 CA GLU A 318 -9. .820 62. .616 16. .073 1. .00 0. .00 XXXX2378

ATOM 2379 C GLU A 318 -9. .072 61. .387 15. .569 1. .00 0. .00 XXXX2379

ATOM 2380 O GLU A 318 -9. .643 60. .536 14. .887 1. .00 0. .00 XXXX2380 Attorney Docket No. 35327-522001 WO

ATOM 2381 CB GLU A 318 -9. .448 63. .839 15. .233 1. .00 0. .00 XXXX2381

ATOM 2382 CG GLU A 318 -9. .663 63. .650 13. .739 1. .00 0. .00 XXXX2382

ATOM 2383 CD GLU A 318 -11. .099 63. .302 13. .397 1. .00 0. .00 XXXX2383

ATOM 2384 OE1 GLU A 318 -12. .010 63. .752 14. .123 1. .00 0. .00 XXXX2384

ATOM 2385 OE2 GLU A 318 -11. .317 62. .574 12. .404 1. .00 0. .00 XXXX2385

ATOM 2386 N ALA A 319 -7. .792 61. .298 15. .915 1. .00 0. .00 XXXX2386

ATOM 2387 CA ALA A 319 -6. .950 60. .191 15. .478 1. .00 0. .00 XXXX2387

ATOM 2388 C ALA A 319 -7. .390 58. .861 16. .085 1. .00 0. .00 XXXX2388

ATOM 2389 O ALA A 319 -7. .225 57. .806 15. .475 1. .00 0. .00 XXXX2389

ATOM 2390 CB ALA A 319 -5. .497 60. .469 15. .828 1. .00 0. .00 XXXX2390

ATOM 2391 N ALA A 320 -7. .949 58. .919 17. .289 1. .00 0. .00 XXXX2391

ATOM 2392 CA ALA A 320 -8. .307 57. .711 18. .025 1. .00 0. .00 XXXX2392

ATOM 2393 C ALA A 320 -9. .453 56. .947 17. .369 1. .00 0. .00 XXXX2393

ATOM 2394 O ALA A 320 -9. .579 55. .737 17. .554 1. .00 0. .00 XXXX2394

ATOM 2395 CB ALA A 320 -8. .667 58. .061 19. .461 1. .00 0. .00 XXXX2395

ATOM 2396 N LYS A 321 -10. .284 57. .654 16. .609 1. .00 0. .00 XXXX2396

ATOM 2397 CA LYS A 321 -11. .444 57. .039 15. .969 1. .00 0. .00 XXXX2397

ATOM 2398 C LYS A 321 -11. .055 55. .886 15. .049 1. .00 0. .00 XXXX2398

ATOM 2399 O LYS A 321 -10. .338 56. .075 14. .066 1. .00 0. .00 XXXX2399

ATOM 2400 CB LYS A 321 -12. .235 58. .082 15. .175 1. .00 0. .00 XXXX2400

ATOM 2401 CG LYS A 321 -12. .812 59. .209 16. .012 1. .00 0. .00 XXXX2401

ATOM 2402 CD LYS A 321 -13. .652 60. .146 15. .160 1. .00 0. .00 XXXX2402

ATOM 2403 CE LYS A 321 -14. .200 61. .302 15. .978 1. .00 0. .00 XXXX2403

ATOM 2404 NZ LYS A 321 -14. .912 62. .288 15. .121 1. .00 0. .00 XXXX2404

ATOM 2405 N GLY A 322 -11. .539 54. .692 15. .375 1. .00 0. .00 XXXX2405

ATOM 2406 CA GLY A 322 -11. .322 53. .524 14. .542 1. .00 0. .00 XXXX2406

ATOM 2407 C GLY A 322 -10. .011 52. .792 14. .766 1. .00 0. .00 XXXX2407

ATOM 2408 O GLY A 322 -9. .758 51. .771 14. .125 1. .00 0. .00 XXXX2408

ATOM 2409 N ILE A 323 -9. .174 53. .297 15. .668 1. .00 0. .00 XXXX2409

ATOM 2410 CA ILE A 323 -7. .888 52. .652 15. .927 1. .00 0. .00 XXXX2410

ATOM 2411 C ILE A 323 -8. .074 51. .263 16. .522 1. .00 0. .00 XXXX2411

ATOM 2412 O ILE A 323 -8. .853 51. .068 17. .458 1. .00 0. .00 XXXX2412

ATOM 2413 CB ILE A 323 -6. .998 53. .486 16. .865 1. .00 0. .00 XXXX2413

ATOM 2414 CGI ILE A 323 -6. .469 54. .719 16. .133 1. .00 0. .00 XXXX2414

ATOM 2415 CD1 ILE A 323 -5. .398 55. .468 16. .899 1. .00 0. .00 XXXX2415

ATOM 2416 CG2 ILE A 323 -5. .820 52. .657 17. .353 1. .00 0. .00 XXXX2416

ATOM 2417 N GLU A 324 -7. .346 50. .301 15. .965 1. .00 0. .00 XXXX2417

ATOM 2418 CA GLU A 324 -7. .446 48. .907 16. .374 1. .00 0. .00 XXXX2418

ATOM 2419 C GLU A 324 -6. .300 48. .498 17. .293 1. .00 0. .00 XXXX2419

ATOM 2420 O GLU A 324 -5. .287 49. .191 17. .391 1. .00 0. .00 XXXX2420

ATOM 2421 CB GLU A 324 -7. .472 47. .998 15. .144 1. .00 0. .00 XXXX2421

ATOM 2422 CG GLU A 324 -8. .600 48. .302 14. .175 1. .00 0. .00 XXXX2422

ATOM 2423 CD GLU A 324 -8. .422 47. .604 12. .842 1. .00 0. .00 XXXX2423

ATOM 2424 OE1 GLU A 324 -7. .262 47. .356 12. .452 1. .00 0. .00 XXXX2424

ATOM 2425 OE2 GLU A 324 -9. .440 47. .304 12. .184 1. .00 0. .00 XXXX2425

ATOM 2426 N PHE A 325 -6. .475 47. .370 17. .972 1. .00 0. .00 XXXX2426

ATOM 2427 CA PHE A 325 -5. .423 46. .798 18. .802 1. .00 0. .00 XXXX2427

ATOM 2428 C PHE A 325 -5. .616 45. .292 18. .937 1. .00 0. .00 XXXX2428

ATOM 2429 O PHE A 325 -6. .718 44. .822 19. .222 1. .00 0. .00 XXXX2429

ATOM 2430 CB PHE A 325 -5. .406 47. .459 20. .183 1. .00 0. .00 XXXX2430

ATOM 2431 CG PHE A 325 -4. .209 47. .093 21. .017 1. .00 0. .00 XXXX2431

ATOM 2432 CD1 PHE A 325 -2. .961 47. .624 20. .734 1. .00 0. .00 XXXX2432

ATOM 2433 CD2 PHE A 325 -4. .331 46. .215 22. .081 1. .00 0. .00 XXXX2433

ATOM 2434 CE1 PHE A 325 -1. .857 47. .288 21. .498 1. .00 0. .00 XXXX2434

ATOM 2435 CE2 PHE A 325 -3. .232 45. .876 22. .850 1. .00 0. .00 XXXX2435

ATOM 2436 CZ PHE A 325 -1. .994 46. .412 22. .558 1. .00 0. .00 XXXX2436

ATOM 2437 N ASN A 326 -4. .544 44. .535 18. .726 1. .00 0. .00 XXXX2437

ATOM 2438 CA ASN A 326 -4. .591 43. .094 18. .940 1. .00 0. .00 XXXX2438

ATOM 2439 C ASN A 326 -4. .482 42. .775 20. .428 1. .00 0. .00 XXXX2439

ATOM 2440 O ASN A 326 -3. .424 42. .383 20. .917 1. .00 0. .00 XXXX2440

ATOM 2441 CB ASN A 326 -3. .480 42. .391 18. .156 1. .00 0. .00 XXXX2441

ATOM 2442 CG ASN A 326 -2. .127 43. .052 18. .336 1. .00 0. .00 XXXX2442

ATOM 2443 OD1 ASN A 326 -2. .022 44. .278 18. .388 1. .00 0. .00 XXXX2443

ATOM 2444 ND2 ASN A 326 -1. .080 42. .239 18. .440 1. .00 0. .00 XXXX2444

ATOM 2445 N ALA A 327 -5. .594 42. .938 21. .138 1. .00 0. .00 XXXX2445

ATOM 2446 CA ALA A 327 -5. .622 42. .752 22. .584 1. .00 0. .00 XXXX2446

ATOM 2447 C ALA A 327 -5. .564 41. .281 22. .967 1. .00 0. .00 XXXX2447 Attorney Docket No. 35327-522001 WO

ATOM 2448 O ALA A 327 -5. .881 40. .410 22. .159 1. .00 0. .00 XXXX2448

ATOM 2449 CB ALA A 327 -6. .868 43. .397 23. .176 1. .00 0. .00 XXXX2449

ATOM 2450 N PRO A 328 -5. .150 41. .003 24. .210 1. .00 0. .00 XXXX2450

ATOM 2451 CA PRO A 328 -5. .137 39. .655 24. .785 1. .00 0. .00 XXXX2451

ATOM 2452 C PRO A 328 -6. .491 38. .956 24. .665 1. .00 0. .00 XXXX2452

ATOM 2453 O PRO A 328 -6. .537 37. .743 24. .469 1. .00 0. .00 XXXX2453

ATOM 2454 CB PRO A 328 -4. .780 39. .910 26. .251 1. .00 0. .00 XXXX2454

ATOM 2455 CG PRO A 328 -3. .953 41. .147 26. .208 1. .00 0. .00 XXXX2455

ATOM 2456 CD PRO A 328 -4. .581 41. .998 25. .137 1. .00 0. .00 XXXX2456

ATOM 2457 N GLU A 329 -7. .576 39. .715 24. .786 1. .00 0. .00 XXXX2457

ATOM 2458 CA GLU A 329 -8. .917 39. .140 24. .743 1. .00 0. .00 XXXX2458

ATOM 2459 C GLU A 329 -9. .340 38. .815 23. .315 1. .00 0. .00 XXXX2459

ATOM 2460 O GLU A 329 -10. .276 38. .046 23. .088 1. .00 0. .00 XXXX2460

ATOM 2461 CB GLU A 329 -9. .933 40. .101 25. .362 1. .00 0. .00 XXXX2461

ATOM 2462 CG GLU A 329 -10. .208 41. .323 24. .494 1. .00 0. .00 XXXX2462

ATOM 2463 CD GLU A 329 -11. .387 42. .143 24. .983 1. .00 0. .00 XXXX2463

ATOM 2464 OE1 GLU A 329 -11. .285 42. .752 26. .069 1. .00 0. .00 XXXX2464

ATOM 2465 OE2 GLU A 329 -12. .417 42. .178 24. .278 1. .00 0. .00 XXXX2465

ATOM 2466 N GLY A 330 -8. .641 39. .408 22. .356 1. .00 0. .00 XXXX2466

ATOM 2467 CA GLY A 330 -9. .031 39. .329 20. .962 1. .00 0. .00 XXXX2467

ATOM 2468 C GLY A 330 -8. .980 40. .713 20. .348 1. .00 0. .00 XXXX2468

ATOM 2469 O GLY A 330 -8. .544 41. .664 20. .997 1. .00 0. .00 XXXX2469

ATOM 2470 N PRO A 331 -9. .428 40. .841 19. .092 1. .00 0. .00 XXXX2470

ATOM 2471 CA PRO A 331 -9. .371 42. .152 18. .440 1. .00 0. .00 XXXX2471

ATOM 2472 C PRO A 331 -10. .318 43. .163 19. .079 1. .00 0. .00 XXXX2472

ATOM 2473 O PRO A 331 -11. .483 42. .854 19. .328 1. .00 0. .00 XXXX2473

ATOM 2474 CB PRO A 331 -9. .791 41. .848 16. .999 1. .00 0. .00 XXXX2474

ATOM 2475 CG PRO A 331 -10. .605 40. .602 17. .097 1. .00 0. .00 XXXX2475

ATOM 2476 CD PRO A 331 -10. .007 39. .805 18. .219 1. .00 0. .00 XXXX2476

ATOM 2477 N VAL A 332 -9. .808 44. .360 19. .342 1. .00 0. .00 XXXX2477

ATOM 2478 CA VAL A 332 -10. .634 45. .461 19. .814 1. .00 0. .00 XXXX2478

ATOM 2479 C VAL A 332 -10. .404 46. .682 18. .935 1. .00 0. .00 XXXX2479

ATOM 2480 O VAL A 332 -9. .462 46. .718 18. .143 1. .00 0. .00 XXXX2480

ATOM 2481 CB VAL A 332 -10. .335 45. .822 21. .283 1. .00 0. .00 XXXX2481

ATOM 2482 CGI VAL A 332 -10. .625 44. .637 22. .193 1. .00 0. .00 XXXX2482

ATOM 2483 CG2 VAL A 332 -8. .891 46. .289 21. .435 1. .00 0. .00 XXXX2483

ATOM 2484 N LYS A 333 -11. .269 47. .677 19. .078 1. .00 0. .00 XXXX2484

ATOM 2485 CA LYS A 333 -11. .188 48. .884 18. .269 1. .00 0. .00 XXXX2485

ATOM 2486 C LYS A 333 -11. .925 50. .015 18. .969 1. .00 0. .00 XXXX2486

ATOM 2487 O LYS A 333 -12. .974 49. .797 19. .574 1. .00 0. .00 XXXX2487

ATOM 2488 CB LYS A 333 -11. .781 48. .663 16. .876 1. .00 0. .00 XXXX2488

ATOM 2489 CG LYS A 333 -11. .893 49. .949 16. .070 1. .00 0. .00 XXXX2489

ATOM 2490 CD LYS A 333 -12. .822 49. .816 14. .877 1. .00 0. .00 XXXX2490

ATOM 2491 CE LYS A 333 -14. .231 50. .257 15. .243 1. .00 0. .00 XXXX2491

ATOM 2492 NZ LYS A 333 -15. .083 50. .492 14. .045 1. .00 0. .00 XXXX2492

ATOM 2493 N ILE A 334 -11. .380 51. .222 18. .890 1. .00 0. .00 XXXX2493

ATOM 2494 CA ILE A 334 -12. .067 52. .373 19. .454 1. .00 0. .00 XXXX2494

ATOM 2495 C ILE A 334 -13. .229 52. .767 18. .551 1. .00 0. .00 XXXX2495

ATOM 2496 O ILE A 334 -13. .033 53. .116 17. .386 1. .00 0. .00 XXXX2496

ATOM 2497 CB ILE A 334 -11. .123 53. .570 19. .640 1. .00 0. .00 XXXX2497

ATOM 2498 CGI ILE A 334 -10. .004 53. .212 20. .621 1. .00 0. .00 XXXX2498

ATOM 2499 CG2 ILE A 334 -11. .893 54. .778 20. .141 1. .00 0. .00 XXXX2499

ATOM 2500 CD1 ILE A 334 -9. .090 54. .369 20. .955 1. .00 0. .00 XXXX2500

ATOM 2501 N ASP A 335 -14. .438 52. .692 19. .095 1. .00 0. .00 XXXX2501

ATOM 2502 CA ASP A 335 -15. .640 53. .089 18. .372 1. .00 0. .00 XXXX2502

ATOM 2503 C ASP A 335 -15. .686 54. .607 18. .244 1. .00 0. .00 XXXX2503

ATOM 2504 O ASP A 335 -15. .881 55. .310 19. .233 1. .00 0. .00 XXXX2504

ATOM 2505 CB ASP A 335 -16. .893 52. .568 19. .085 1. .00 0. .00 XXXX2505

ATOM 2506 CG ASP A 335 -18. .163 52. .767 18. .273 1. .00 0. .00 XXXX2506

ATOM 2507 OD1 ASP A 335 -18. .156 53. .565 17. .311 1. .00 0. .00 XXXX2507

ATOM 2508 OD2 ASP A 335 -19. .179 52. .118 18. .599 1. .00 0. .00 XXXX2508

ATOM 2509 N GLY A 336 -15. .499 55. .102 17. .024 1. .00 0. .00 XXXX2509

ATOM 2510 CA GLY A 336 -15. .538 56. .529 16. .760 1. .00 0. .00 XXXX2510

ATOM 2511 C GLY A 336 -16. .835 57. .200 17. .172 1. .00 0. .00 XXXX2511

ATOM 2512 O GLY A 336 -16. .859 58. .398 17. .457 1. .00 0. .00 XXXX2512

ATOM 2513 N ASP A 337 -17. .916 56. .428 17. .208 1. .00 0. .00 XXXX2513

ATOM 2514 CA ASP A 337 -19. .229 56. .959 17. .564 1. .00 0. .00 XXXX2514 Attorney Docket No. 35327-522001 WO

ATOM 2515 C ASP A 337 -19. .320 57. .441 19. .011 1. .00 0. .00 XXXX2515

ATOM 2516 O ASP A 337 -20. .075 58. .365 19. .313 1. .00 0. .00 XXXX2516

ATOM 2517 CB ASP A 337 -20. .312 55. .906 17. .313 1. .00 0. .00 XXXX2517

ATOM 2518 CG ASP A 337 -20. .620 55. .723 15. .841 1. .00 0. .00 XXXX2518

ATOM 2519 OD1 ASP A 337 -20. .189 56. .572 15. .033 1. .00 0. .00 XXXX2519

ATOM 2520 OD2 ASP A 337 -21. .295 54. .734 15. .492 1. .00 0. .00 XXXX2520

ATOM 2521 N ASN A 338 -18. .557 56. .822 19. .907 1. .00 0. .00 XXXX2521

ATOM 2522 CA ASN A 338 -18. .741 57. .071 21. .334 1. .00 0. .00 XXXX2522

ATOM 2523 C ASN A 338 -17. .491 56. .873 22. .188 1. .00 0. .00 XXXX2523

ATOM 2524 O ASN A 338 -17. .551 56. .972 23. .413 1. .00 0. .00 XXXX2524

ATOM 2525 CB ASN A 338 -19. .866 56. .177 21. .860 1. .00 0. .00 XXXX2525

ATOM 2526 CG ASN A 338 -19. .669 54. .720 21. .491 1. .00 0. .00 XXXX2526

ATOM 2527 OD1 ASN A 338 -18. .542 54. .227 21. .444 1. .00 0. .00 XXXX2527

ATOM 2528 ND2 ASN A 338 -20. .766 54. .025 21. .219 1. .00 0. .00 XXXX2528

ATOM 2529 N GLN A 339 -16. .364 56. .594 21. .540 1. .00 0. .00 XXXX2529

ATOM 2530 CA GLN A 339 -15. .084 56. .460 22. .234 1. .00 0. .00 XXXX2530

ATOM 2531 C GLN A 339 -15. .061 55. .291 23. .224 1. .00 0. .00 XXXX2531

ATOM 2532 O GLN A 339 -14. .222 55. .246 24. .125 1. .00 0. .00 XXXX2532

ATOM 2533 CB GLN A 339 -14. .733 57. .772 22. .943 1. .00 0. .00 XXXX2533

ATOM 2534 CG GLN A 339 -14. .724 58. .970 22. .001 1. .00 0. .00 XXXX2534

ATOM 2535 CD GLN A 339 -14. .136 60. .221 22. .622 1. .00 0. .00 XXXX2535

ATOM 2536 OE1 GLN A 339 -13. .869 61. .202 21. .927 1. .00 0. .00 XXXX2536

ATOM 2537 NE2 GLN A 339 -13. .934 60. .198 23. .934 1. .00 0. .00 XXXX2537

ATOM 2538 N HIS A 340 -15. .993 54. .357 23. .054 1. .00 0. .00 XXXX2538

ATOM 2539 CA HIS A 340 -15. .944 53. .071 23. .749 1. .00 0. .00 XXXX2539

ATOM 2540 C HIS A 340 -15. .174 52. .053 22. .905 1. .00 0. .00 XXXX2540

ATOM 2541 O HIS A 340 -14. .686 52. .380 21. .823 1. .00 0. .00 XXXX2541

ATOM 2542 CB HIS A 340 -17. .355 52. .554 24. .049 1. .00 0. .00 XXXX2542

ATOM 2543 CG HIS A 340 -18. .081 53. .333 25. .103 1. .00 0. .00 XXXX2543

ATOM 2544 ND1 HIS A 340 -18. .343 54. .682 24. .988 1. .00 0. .00 XXXX2544

ATOM 2545 CD2 HIS A 340 -18. .612 52. .947 26. .287 1. .00 0. .00 XXXX2545

ATOM 2546 CE1 HIS A 340 -19. .000 55. .093 26. .058 1. .00 0. .00 XXXX2546

ATOM 2547 NE2 HIS A 340 -19. .175 54. .060 26. .862 1. .00 0. .00 XXXX2547

ATOM 2548 O LEU A 341 -16. .282 48. .308 22. .766 1. .00 0. .00 XXXX2548

ATOM 2549 N LEU A 341 -15. .066 50. .822 23. .399 1. .00 0. .00 XXXX2549

ATOM 2550 CA LEU A 341 -14. .371 49. .759 22. .670 1. .00 0. .00 XXXX2550

ATOM 2551 C LEU A 341 -15. .301 48. .682 22. .123 1. .00 0. .00 XXXX2551

ATOM 2552 CB LEU A 341 -13. .332 49. .077 23. .567 1. .00 0. .00 XXXX2552

ATOM 2553 CG LEU A 341 -11. .973 49. .718 23. .842 1. .00 0. .00 XXXX2553

ATOM 2554 CD1 LEU A 341 -11. .146 48. .789 24. .722 1. .00 0. .00 XXXX2554

ATOM 2555 CD2 LEU A 341 -11. .239 50. .014 22. .544 1. .00 0. .00 XXXX2555

ATOM 2556 N TYR A 342 -14. .982 48. .187 20. .930 1. .00 0. .00 XXXX2556

ATOM 2557 CA TYR A 342 -15. .501 46. .900 20. .484 1. .00 0. .00 XXXX2557

ATOM 2558 C TYR A 342 -14. .879 45. .808 21. .343 1. .00 0. .00 XXXX2558

ATOM 2559 O TYR A 342 -13. .655 45. .681 21. .398 1. .00 0. .00 XXXX2559

ATOM 2560 CB TYR A 342 -15. .185 46. .646 19. .008 1. .00 0. .00 XXXX2560

ATOM 2561 CG TYR A 342 -16. .077 47. .366 18. .022 1. .00 0. .00 XXXX2561

ATOM 2562 CD1 TYR A 342 -16. .048 48. .749 17. .902 1. .00 0. .00 XXXX2562

ATOM 2563 CD2 TYR A 342 -16. .933 46. .654 17. .192 1. .00 0. .00 XXXX2563

ATOM 2564 CE1 TYR A 342 -16. .861 49. .402 16. .990 1. .00 0. .00 XXXX2564

ATOM 2565 CE2 TYR A 342 -17. .745 47. .296 16. .280 1. .00 0. .00 XXXX2565

ATOM 2566 CZ TYR A 342 -17. .706 48. .670 16. .183 1. .00 0. .00 XXXX2566

ATOM 2567 OH TYR A 342 -18. .515 49. .309 15. .273 1. .00 0. .00 XXXX2567

ATOM 2568 N LYS A 343 -15. .713 45. .019 22. .013 1. .00 0. .00 XXXX2568

ATOM 2569 CA LYS A 343 -15. .204 43. .957 22. .872 1. .00 0. .00 XXXX2569

ATOM 2570 C LYS A 343 -16. .005 42. .666 22. .735 1. .00 0. .00 XXXX2570

ATOM 2571 O LYS A 343 -17. .205 42. .688 22. .462 1. .00 0. .00 XXXX2571

ATOM 2572 CB LYS A 343 -15. .198 44. .409 24. .335 1. .00 0. .00 XXXX2572

ATOM 2573 CG LYS A 343 -14. .585 45. .784 24. .559 1. .00 0. .00 XXXX2573

ATOM 2574 CD LYS A 343 -14. .347 46. .051 26. .036 1. .00 0. .00 XXXX2574

ATOM 2575 CE LYS A 343 -13. .164 45. .247 26. .554 1. .00 0. .00 XXXX2575

ATOM 2576 NZ LYS A 343 -12. .938 45. .466 28. .008 1. .00 0. .00 XXXX2576

ATOM 2577 N THR A 344 -15. .323 41. .542 22. .922 1. .00 0. .00 XXXX2577

ATOM 2578 CA THR A 344 -15. .974 40. .240 22. .954 1. .00 0. .00 XXXX2578

ATOM 2579 C THR A 344 -16. .641 40. .031 24. .309 1. .00 0. .00 XXXX2579

ATOM 2580 O THR A 344 -16. .114 40. .457 25. .334 1. .00 0. .00 XXXX2580

ATOM 2581 CB THR A 344 -14. .972 39. .101 22. .694 1. .00 0. .00 XXXX2581 Attorney Docket No. 35327-522001 WO

ATOM 2582 OG1 THR A 344 -14. .387 39. .263 21. .395 1. .00 0. .00 XXXX2582

ATOM 2583 CG2 THR A 344 -15. .666 37. .750 22. .774 1. .00 0. .00 XXXX2583

ATOM 2584 N VAL A 345 -17. .799 39. .381 24. .315 1. .00 0. .00 XXXX2584

ATOM 2585 CA VAL A 345 -18. .483 39. .078 25. .567 1. .00 0. .00 XXXX2585

ATOM 2586 C VAL A 345 -18. .241 37. .630 25. .970 1. .00 0. .00 XXXX2586

ATOM 2587 O VAL A 345 -18. .361 36. .727 25. .145 1. .00 0. .00 XXXX2587

ATOM 2588 CB VAL A 345 -19. .994 39. .328 25. .460 1. .00 0. .00 XXXX2588

ATOM 2589 CGI VAL A 345 -20. .672 39. .036 26. .789 1. .00 0. .00 XXXX2589

ATOM 2590 CG2 VAL A 345 -20. .261 40. .757 25. .013 1. .00 0. .00 XXXX2590

ATOM 2591 N ARG A 346 -17. .902 37. .413 27. .239 1. .00 0. .00 XXXX2591

ATOM 2592 CA ARG A 346 -17. .636 36. .066 27. .731 1. .00 0. .00 XXXX2592

ATOM 2593 C ARG A 346 -18. .294 35. .850 29. .091 1. .00 0. .00 XXXX2593

ATOM 2594 O ARG A 346 -18. .254 36. .727 29. .956 1. .00 0. .00 XXXX2594

ATOM 2595 CB ARG A 346 -16. .130 35. .822 27. .856 1. .00 0. .00 XXXX2595

ATOM 2596 CG ARG A 346 -15. .292 36. .437 26. .746 1. .00 0. .00 XXXX2596

ATOM 2597 CD ARG A 346 -13. .810 36. .130 26. .937 1. .00 0. .00 XXXX2597

ATOM 2598 NE ARG A 346 -12. .994 36. .556 25. .798 1. .00 0. .00 XXXX2598

ATOM 2599 CZ ARG A 346 -12. .634 35. .788 24. .777 1. .00 0. .00 XXXX2599

ATOM 2600 NH1 ARG A 346 -13. .016 34. .521 24. .720 1. .00 0. .00 XXXX2600

ATOM 2601 NH2 ARG A 346 -11. .886 36. .297 23. .806 1. .00 0. .00 XXXX2601

ATOM 2602 N ILE A 347 -18. .892 34. .679 29. .275 1. .00 0. .00 XXXX2602

ATOM 2603 CA ILE A 347 -19. .439 34. .291 30. .568 1. .00 0. .00 XXXX2603

ATOM 2604 C ILE A 347 -18. .739 33. .023 31. .048 1. .00 0. .00 XXXX2604

ATOM 2605 O ILE A 347 -18. .508 32. .102 30. .265 1. .00 0. .00 XXXX2605

ATOM 2606 CB ILE A 347 -20. .959 34. .062 30. .500 1. .00 0. .00 XXXX2606

ATOM 2607 CGI ILE A 347 -21. .673 35. .358 30. .105 1. .00 0. .00 XXXX2607

ATOM 2608 CG2 ILE A 347 -21. .479 33. .541 31. .830 1. .00 0. .00 XXXX2608

ATOM 2609 CD1 ILE A 347 -23. .171 35. .207 29. .928 1. .00 0. .00 XXXX2609

ATOM 2610 N GLY A 348 -18. .392 32. .979 32. .329 1. .00 0. .00 XXXX2610

ATOM 2611 CA GLY A 348 -17. .651 31. .850 32. .861 1. .00 0. .00 XXXX2611

ATOM 2612 C GLY A 348 -17. .961 31. .520 34. .306 1. .00 0. .00 XXXX2612

ATOM 2613 O GLY A 348 -18. .590 32. .306 35. .016 1. .00 0. .00 XXXX2613

ATOM 2614 N GLU A 349 -17. .516 30. .346 34. .743 1. .00 0. .00 XXXX2614

ATOM 2615 CA GLU A 349 -17. .659 29. .951 36. .138 1. .00 0. .00 XXXX2615

ATOM 2616 C GLU A 349 -16. .298 29. .905 36. .823 1. .00 0. .00 XXXX2616

ATOM 2617 O GLU A 349 -15. .285 29. .580 36. .202 1. .00 0. .00 XXXX2617

ATOM 2618 CB GLU A 349 -18. .355 28. .593 36. .255 1. .00 0. .00 XXXX2618

ATOM 2619 CG GLU A 349 -17. .580 27. .430 35. .659 1. .00 0. .00 XXXX2619

ATOM 2620 CD GLU A 349 -18. .232 26. .090 35. .950 1. .00 0. .00 XXXX2620

ATOM 2621 OE1 GLU A 349 -18. .860 25. .954 37. .022 1. .00 0. .00 XXXX2621

ATOM 2622 OE2 GLU A 349 -18. .115 25. .174 35. .109 1. .00 0. .00 XXXX2622

ATOM 2623 N ILE A 350 -16. .285 30. .239 38. .107 1. .00 0. .00 XXXX2623

ATOM 2624 CA ILE A 350 -15. .045 30. .306 38. .867 1. .00 0. .00 XXXX2624

ATOM 2625 C ILE A 350 -14. .586 28. .917 39. .295 1. .00 0. .00 XXXX2625

ATOM 2626 O ILE A 350 -15. .362 28. .140 39. .853 1. .00 0. .00 XXXX2626

ATOM 2627 CB ILE A 350 -15. .207 31. .203 40. .106 1. .00 0. .00 XXXX2627

ATOM 2628 CGI ILE A 350 -15. .692 32. .593 39. .687 1. .00 0. .00 XXXX2628

ATOM 2629 CG2 ILE A 350 -13. .899 31. .287 40. .878 1. .00 0. .00 XXXX2629

ATOM 2630 CD1 ILE A 350 -16. .161 33. .459 40. .836 1. .00 0. .00 XXXX2630

ATOM 2631 N LEU A 351 -13. .320 28. .611 39. .028 1. .00 0. .00 XXXX2631

ATOM 2632 CA LEU A 351 -12. .757 27. .304 39. .350 1. .00 0. .00 XXXX2632

ATOM 2633 C LEU A 351 -12. .110 27. .296 40. .732 1. .00 0. .00 XXXX2633

ATOM 2634 O LEU A 351 -11. .952 28. .341 41. .362 1. .00 0. .00 XXXX2634

ATOM 2635 CB LEU A 351 -11. .734 26. .884 38. .292 1. .00 0. .00 XXXX2635

ATOM 2636 CG LEU A 351 -12. .255 26. .738 36. .860 1. .00 0. .00 XXXX2636

ATOM 2637 CD1 LEU A 351 -11. .108 26. .464 35. .896 1. .00 0. .00 XXXX2637

ATOM 2638 CD2 LEU A 351 -13. .306 25. .640 36. .777 1. .00 0. .00 XXXX2638

ATOM 2639 N GLU A 352 -11. .746 26. .104 41. .192 1. .00 0. .00 XXXX2639

ATOM 2640 CA GLU A 352 -11. .170 25. .918 42. .519 1. .00 0. .00 XXXX2640

ATOM 2641 C GLU A 352 -9. .900 26. .746 42. .725 1. .00 0. .00 XXXX2641

ATOM 2642 O GLU A 352 -9. .612 27. .183 43. .839 1. .00 0. .00 XXXX2642

ATOM 2643 CB GLU A 352 -10. .874 24. .435 42. .755 1. .00 0. .00 XXXX2643

ATOM 2644 CG GLU A 352 -10. .297 24. .114 44. .122 1. .00 0. .00 XXXX2644

ATOM 2645 CD GLU A 352 -9. .880 22. .661 44. .250 1. .00 0. .00 XXXX2645

ATOM 2646 OE1 GLU A 352 -9. .159 22. .165 43. .359 1. .00 0. .00 XXXX2646

ATOM 2647 OE2 GLU A 352 -10. .274 22. .014 45. .243 1. .00 0. .00 XXXX2647

ATOM 2648 N ASN A 353 -9. .146 26. .965 41. .652 1. .00 0. .00 XXXX2648 Attorney Docket No. 35327-522001 WO

ATOM 2649 CA ASN A 353 -7. .907 27. .731 41. .743 1. .00 0. .00 XXXX2649

ATOM 2650 C ASN A 353 -8. .110 29. .227 41. .501 1. .00 0. .00 XXXX2650

ATOM 2651 O ASN A 353 -7. .145 29. .988 41. .432 1. .00 0. .00 XXXX2651

ATOM 2652 CB ASN A 353 -6. .873 27. .179 40. .759 1. .00 0. .00 XXXX2652

ATOM 2653 CG ASN A 353 -7. .319 27. .293 39. .316 1. .00 0. .00 XXXX2653

ATOM 2654 OD1 ASN A 353 -8. .480 27. .586 39. .032 1. .00 0. .00 XXXX2654

ATOM 2655 ND2 ASN A 353 -6. .395 27. .052 38. .392 1. .00 0. .00 XXXX2655

ATOM 2656 N GLY A 354 -9. .366 29. .644 41. .375 1. .00 0. .00 XXXX2656

ATOM 2657 CA GLY A 354 -9. .685 31. .048 41. .181 1. .00 0. .00 XXXX2657

ATOM 2658 C GLY A 354 -9. .704 31. .505 39. .733 1. .00 0. .00 XXXX2658

ATOM 2659 O GLY A 354 -10. .056 32. .649 39. .444 1. .00 0. .00 XXXX2659

ATOM 2660 N GLN A 355 -9. .330 30. .617 38. .818 1. .00 0. .00 XXXX2660

ATOM 2661 CA GLN A 355 -9. .386 30. .933 37. .395 1. .00 0. .00 XXXX2661

ATOM 2662 C GLN A 355 -10. .797 30. .743 36. .850 1. .00 0. .00 XXXX2662

ATOM 2663 O GLN A 355 -11. .660 30. .183 37. .526 1. .00 0. .00 XXXX2663

ATOM 2664 CB GLN A 355 -8. .394 30. .072 36. .614 1. .00 0. .00 XXXX2664

ATOM 2665 CG GLN A 355 -6. .944 30. .396 36. .918 1. .00 0. .00 XXXX2665

ATOM 2666 CD GLN A 355 -6. .537 31. .767 36. .412 1. .00 0. .00 XXXX2666

ATOM 2667 OE1 GLN A 355 -6. .607 32. .044 35. .214 1. .00 0. .00 XXXX2667

ATOM 2668 NE2 GLN A 355 -6. .114 32. .634 37. .325 1. .00 0. .00 XXXX2668

ATOM 2669 N ILE A 356 -11. .025 31. .206 35. .625 1. .00 0. .00 XXXX2669

ATOM 2670 CA ILE A 356 -12. .357 31. .157 35. .035 1. .00 0. .00 XXXX2670

ATOM 2671 C ILE A 356 -12. .451 30. .118 33. .924 1. .00 0. .00 XXXX2671

ATOM 2672 O ILE A 356 -11. .575 30. .025 33. .063 1. .00 0. .00 XXXX2672

ATOM 2673 CB ILE A 356 -12. .772 32. .527 34. .458 1. .00 0. .00 XXXX2673

ATOM 2674 CGI ILE A 356 -12. .537 33. .640 35. .481 1. .00 0. .00 XXXX2674

ATOM 2675 CG2 ILE A 356 -14. .227 32. .495 33. .998 1. .00 0. .00 XXXX2675

ATOM 2676 CD1 ILE A 356 -13. .311 33. .465 36. .769 1. .00 0. .00 XXXX2676

ATOM 2677 N ARG A 357 -13. .522 29. .333 33. .958 1. .00 0. .00 XXXX2677

ATOM 2678 CA ARG A 357 -13. .852 28. .421 32. .873 1. .00 0. .00 XXXX2678

ATOM 2679 C ARG A 357 -14. .952 29. .028 32. .014 1. .00 0. .00 XXXX2679

ATOM 2680 O ARG A 357 -16. .069 29. .242 32. .485 1. .00 0. .00 XXXX2680

ATOM 2681 CB ARG A 357 -14. .284 27. .062 33. .427 1. .00 0. .00 XXXX2681

ATOM 2682 CG ARG A 357 -14. .749 26. .065 32. .380 1. .00 0. .00 XXXX2682

ATOM 2683 CD ARG A 357 -15. .100 24. .741 33. .038 1. .00 0. .00 XXXX2683

ATOM 2684 NE ARG A 357 -15. .602 23. .748 32. .093 1. .00 0. .00 XXXX2684

ATOM 2685 CZ ARG A 357 -16. .888 23. .458 31. .926 1. .00 0. .00 XXXX2685

ATOM 2686 NH1 ARG A 357 -17. .810 24. .086 32. .642 1. .00 0. .00 XXXX2686

ATOM 2687 NH2 ARG A 357 -17. .253 22. .537 31. .044 1. .00 0. .00 XXXX2687

ATOM 2688 N GLU A 358 -14. .634 29. .312 30. .755 1. .00 0. .00 XXXX2688

ATOM 2689 CA GLU A 358 -15. .595 29. .955 29. .869 1. .00 0. .00 XXXX2689

ATOM 2690 C GLU A 358 -16. .735 29. .006 29. .520 1. .00 0. .00 XXXX2690

ATOM 2691 O GLU A 358 -16. .506 27. .869 29. .113 1. .00 0. .00 XXXX2691

ATOM 2692 CB GLU A 358 -14. .911 30. .449 28. .593 1. .00 0. .00 XXXX2692

ATOM 2693 CG GLU A 358 -15. .858 31. .107 27. .604 1. .00 0. .00 XXXX2693

ATOM 2694 CD GLU A 358 -15. .139 31. .679 26. .397 1. .00 0. .00 XXXX2694

ATOM 2695 OE1 GLU A 358 -14. .455 32. .713 26. .545 1. .00 0. .00 XXXX2695

ATOM 2696 OE2 GLU A 358 -15. .259 31. .094 25. .301 1. .00 0. .00 XXXX2696

ATOM 2697 N LEU A 359 -17. .963 29. .485 29. .687 1. .00 0. .00 XXXX2697

ATOM 2698 CA LEU A 359 -19. .148 28. .694 29. .386 1. .00 0. .00 XXXX2698

ATOM 2699 C LEU A 359 -19. .801 29. .158 28. .088 1. .00 0. .00 XXXX2699

ATOM 2700 O LEU A 359 -20. .470 28. .385 27. .405 1. .00 0. .00 XXXX2700

ATOM 2701 CB LEU A 359 -20. .156 28. .782 30. .534 1. .00 0. .00 XXXX2701

ATOM 2702 CG LEU A 359 -19. .674 28. .375 31. .927 1. .00 0. .00 XXXX2702

ATOM 2703 CD1 LEU A 359 -20. .766 28. .615 32. .958 1. .00 0. .00 XXXX2703

ATOM 2704 CD2 LEU A 359 -19. .233 26. .919 31. .938 1. .00 0. .00 XXXX2704

ATOM 2705 N TRP A 360 -19. .603 30. .430 27. .757 1. .00 0. .00 XXXX2705

ATOM 2706 CA TRP A 360 -20. .282 31. .041 26. .621 1. .00 0. .00 XXXX2706

ATOM 2707 C TRP A 360 -19. .572 32. .316 26. .177 1. .00 0. .00 XXXX2707

ATOM 2708 O TRP A 360 -18. .970 33. .013 26. .991 1. .00 0. .00 XXXX2708

ATOM 2709 CB TRP A 360 -21. .741 31. .342 26. .984 1. .00 0. .00 XXXX2709

ATOM 2710 CG TRP A 360 -22. .518 32. .027 25. .903 1. .00 0. .00 XXXX2710

ATOM 2711 CD1 TRP A 360 -23. .293 31. .436 24. .948 1. .00 0. .00 XXXX2711

ATOM 2712 CD2 TRP A 360 -22. .603 33. .439 25. .671 1. .00 0. .00 XXXX2712

ATOM 2713 NE1 TRP A 360 -23. .851 32. .392 24. .133 1. .00 0. .00 XXXX2713

ATOM 2714 CE2 TRP A 360 -23. .442 33. .629 24. .556 1. .00 0. .00 XXXX2714

ATOM 2715 CE3 TRP A 360 -22. .046 34. .560 26. .296 1. .00 0. .00 XXXX2715 Attorney Docket No. 35327-522001 WO

ATOM 2716 CZ2 TRP A 360 -23. .740 34. .894 24. .052 1. .00 0. .00 XXXX2716

ATOM 2717 CZ3 TRP A 360 -22. .343 35. .816 25. .794 1. .00 0. .00 XXXX2717

ATOM 2718 CH2 TRP A 360 -23. .183 35. .972 24. .684 1. .00 0. .00 XXXX2718

ATOM 2719 N LYS A 361 -19. .644 32. .618 24. .885 1. .00 0. .00 XXXX2719

ATOM 2720 CA LYS A 361 -19. .105 33. .872 24. .368 1. .00 0. .00 XXXX2720

ATOM 2721 C LYS A 361 -19. .741 34. .246 23. .037 1. .00 0. .00 XXXX2721

ATOM 2722 O LYS A 361 -20. .352 33. .409 22. .372 1. .00 0. .00 XXXX2722

ATOM 2723 CB LYS A 361 -17. .585 33. .788 24. .203 1. .00 0. .00 XXXX2723

ATOM 2724 CG LYS A 361 -17. .132 32. .927 23. .031 1. .00 0. .00 XXXX2724

ATOM 2725 CD LYS A 361 -15. .651 33. .116 22. .750 1. .00 0. .00 XXXX2725

ATOM 2726 CE LYS A 361 -15. .155 32. .152 21. .684 1. .00 0. .00 XXXX2726

ATOM 2727 NZ LYS A 361 -13. .716 32. .388 21. .369 1. .00 0. .00 XXXX2727

ATOM 2728 N THR A 362 -19. .594 35. .510 22. .655 1. .00 0. .00 XXXX2728

ATOM 2729 CA THR A 362 -19. .992 35. .948 21. .325 1. .00 0. .00 XXXX2729

ATOM 2730 C THR A 362 -18. .936 35. .510 20. .315 1. .00 0. .00 XXXX2730

ATOM 2731 O THR A 362 -17. .761 35. .385 20. .655 1. .00 0. .00 XXXX2731

ATOM 2732 CB THR A 362 -20. .183 37. .475 21. .256 1. .00 0. .00 XXXX2732

ATOM 2733 OG1 THR A 362 -18. .989 38. .128 21. .704 1. .00 0. .00 XXXX2733

ATOM 2734 CG2 THR A 362 -21. .349 37. .909 22. .132 1. .00 0. .00 XXXX2734

ATOM 2735 N ASN A 363 -19. .353 35. .285 19. .073 1. .00 0. .00 XXXX2735

ATOM 2736 CA ASN A 363 -18. .437 34. .799 18. .048 1. .00 0. .00 XXXX2736

ATOM 2737 C ASN A 363 -17. .560 35. .912 17. .488 1. .00 0. .00 XXXX2737

ATOM 2738 O ASN A 363 -16. .540 35. .653 16. .846 1. .00 0. .00 XXXX2738

ATOM 2739 CB ASN A 363 -19. .215 34. .129 16. .916 1. .00 0. .00 XXXX2739

ATOM 2740 CG ASN A 363 -19. .865 32. .831 17. .348 1. .00 0. .00 XXXX2740

ATOM 2741 OD1 ASN A 363 -21. .079 32. .662 17. .231 1. .00 0. .00 XXXX2741

ATOM 2742 ND2 ASN A 363 -19. .060 31. .905 17. .858 1. .00 0. .00 XXXX2742

ATOM 2743 N LYS A 364 -17. .961 37. .153 17. .742 1. .00 0. .00 XXXX2743

ATOM 2744 CA LYS A 364 -17. .186 38. .316 17. .329 1. .00 0. .00 XXXX2744

ATOM 2745 C LYS A 364 -17. .270 39. .407 18. .388 1. .00 0. .00 XXXX2745

ATOM 2746 O LYS A 364 -18. .127 39. .353 19. .270 1. .00 0. .00 XXXX2746

ATOM 2747 CB LYS A 364 -17. .682 38. .845 15. .983 1. .00 0. .00 XXXX2747

ATOM 2748 CG LYS A 364 -17. .562 37. .846 14. .845 1. .00 0. .00 XXXX2748

ATOM 2749 CD LYS A 364 -18. .157 38. .399 13. .562 1. .00 0. .00 XXXX2749

ATOM 2750 CE LYS A 364 -18. .057 37. .393 12. .427 1. .00 0. .00 XXXX2750

ATOM 2751 NZ LYS A 364 -18. .680 37. .909 11. .176 1. .00 0. .00 XXXX2751

ATOM 2752 N PRO A 365 -16. .374 40. .400 18. .310 1. .00 0. .00 XXXX2752

ATOM 2753 CA PRO A 365 -16. .495 41. .568 19. .187 1. .00 0. .00 XXXX2753

ATOM 2754 C PRO A 365 -17. .820 42. .290 18. .967 1. .00 0. .00 XXXX2754

ATOM 2755 O PRO A 365 -18. .323 42. .319 17. .844 1. .00 0. .00 XXXX2755

ATOM 2756 CB PRO A 365 -15. .314 42. .447 18. .767 1. .00 0. .00 XXXX2756

ATOM 2757 CG PRO A 365 -14. .326 41. .493 18. .179 1. .00 0. .00 XXXX2757

ATOM 2758 CD PRO A 365 -15. .148 40. .439 17. .496 1. .00 0. .00 XXXX2758

ATOM 2759 N VAL A 366 -18. .373 42. .865 20. .029 1. .00 0. .00 XXXX2759

ATOM 2760 CA VAL A 366 -19. .647 43. .569 19. .947 1. .00 0. .00 XXXX2760

ATOM 2761 C VAL A 366 -19. .437 45. .079 19. .964 1. .00 0. .00 XXXX2761

ATOM 2762 O VAL A 366 -18. .663 45. .594 20. .771 1. .00 0. .00 XXXX2762

ATOM 2763 CB VAL A 366 -20. .581 43. .171 21. .103 1. .00 0. .00 XXXX2763

ATOM 2764 CGI VAL A 366 -21. .907 43. .912 20. .996 1. .00 0. .00 XXXX2764

ATOM 2765 CG2 VAL A 366 -20. .802 41. .665 21. .107 1. .00 0. .00 XXXX2765

ATOM 2766 N LYS A 367 -20. .121 45. .785 19. .068 1. .00 0. .00 XXXX2766

ATOM 2767 CA LYS A 367 -20. .066 47. .242 19. .053 1. .00 0. .00 XXXX2767

ATOM 2768 C LYS A 367 -20. .631 47. .801 20. .352 1. .00 0. .00 XXXX2768

ATOM 2769 O LYS A 367 -21. .714 47. .405 20. .778 1. .00 0. .00 XXXX2769

ATOM 2770 CB LYS A 367 -20. .834 47. .805 17. .854 1. .00 0. .00 XXXX2770

ATOM 2771 CG LYS A 367 -20. .685 49. .309 17. .672 1. .00 0. .00 XXXX2771

ATOM 2772 CD LYS A 367 -21. .463 49. .803 16. .461 1. .00 0. .00 XXXX2772

ATOM 2773 CE LYS A 367 -21. .107 51. .244 16. .120 1. .00 0. .00 XXXX2773

ATOM 2774 NZ LYS A 367 -21. .412 52. .182 17. .235 1. .00 0. .00 XXXX2774

ATOM 2775 N PRO A 368 -19. .893 48. .724 20. .988 1. .00 0. .00 XXXX2775

ATOM 2776 CA PRO A 368 -20. .341 49. .339 22. .242 1. .00 0. .00 XXXX2776

ATOM 2777 C PRO A 368 -21. .603 50. .172 22. .049 1. .00 0. .00 XXXX2777

ATOM 2778 O PRO A 368 -21. .702 50. .935 21. .086 1. .00 0. .00 XXXX2778

ATOM 2779 CB PRO A 368 -19. .155 50. .220 22. .648 1. .00 0. .00 XXXX2779

ATOM 2780 CG PRO A 368 -18. .436 50. .497 21. .371 1. .00 0. .00 XXXX2780

ATOM 2781 CD PRO A 368 -18. .589 49. .250 20. .550 1. .00 0. .00 XXXX2781

ATOM 2782 N ASP A 369 -22. .552 50. .022 22. .967 1. .00 0. .00 XXXX2782 Attorney Docket No. 35327-522001 WO

ATOM 2783 CA ASP A 369 -23. .852 50. .674 22. .862 1. .00 0. .00 XXXX2783

ATOM 2784 C ASP A 369 -24. .293 51. .182 24. .233 1. .00 0. .00 XXXX2784

ATOM 2785 O ASP A 369 -25. .224 50. .645 24. .830 1. .00 0. .00 XXXX2785

ATOM 2786 CB ASP A 369 -24. .883 49. .698 22. .286 1. .00 0. .00 XXXX2786

ATOM 2787 CG ASP A 369 -26. .217 50. .356 21. .987 1. .00 0. .00 XXXX2787

ATOM 2788 OD1 ASP A 369 -26. .309 51. .600 22. .057 1. .00 0. .00 XXXX2788

ATOM 2789 OD2 ASP A 369 -27. .178 49. .619 21. .677 1. .00 0. .00 XXXX2789

ATOM 2790 N PRO A 370 -23. .619 52. .228 24. .734 1. .00 0. .00 XXXX2790

ATOM 2791 CA PRO A 370 -23. .806 52. .728 26. .103 1. .00 0. .00 XXXX2791

ATOM 2792 C PRO A 370 -25. .222 53. .223 26. .402 1. .00 0. .00 XXXX2792

ATOM 2793 O PRO A 370 -25. .658 53. .142 27. .550 1. .00 0. .00 XXXX2793

ATOM 2794 CB PRO A 370 -22. .805 53. .886 26. .192 1. .00 0. .00 XXXX2794

ATOM 2795 CG PRO A 370 -22. .534 54. .274 24. .775 1. .00 0. .00 XXXX2795

ATOM 2796 CD PRO A 370 -22. .602 52. .999 24. .001 1. .00 0. .00 XXXX2796

ATOM 2797 N TYR A 371 -25. .930 53. .722 25. .394 1. .00 0. .00 XXXX2797

ATOM 2798 CA TYR A 371 -27. .285 54. .218 25. .614 1. .00 0. .00 XXXX2798

ATOM 2799 C TYR A 371 -28. .332 53. .179 25. .227 1. .00 0. .00 XXXX2799

ATOM 2800 O TYR A 371 -29. .529 53. .466 25. .218 1. .00 0. .00 XXXX2800

ATOM 2801 CB TYR A 371 -27. .514 55. .520 24. .846 1. .00 0. .00 XXXX2801

ATOM 2802 CG TYR A 371 -26. .791 56. .702 25. .452 1. .00 0. .00 XXXX2802

ATOM 2803 CD1 TYR A 371 -27. .344 57. .411 26. .512 1. .00 0. .00 XXXX2803

ATOM 2804 CD2 TYR A 371 -25. .555 57. .109 24. .968 1. .00 0. .00 XXXX2804

ATOM 2805 CE1 TYR A 371 -26. .684 58. .490 27. .074 1. .00 0. .00 XXXX2805

ATOM 2806 CE2 TYR A 371 -24. .889 58. .187 25. .522 1. .00 0. .00 XXXX2806

ATOM 2807 CZ TYR A 371 -25. .457 58. .873 26. .573 1. .00 0. .00 XXXX2807

ATOM 2808 OH TYR A 371 -24. .796 59. .946 27. .125 1. .00 0. .00 XXXX2808

ATOM 2809 N LEU A 372 -27. .867 51. .973 24. .913 1. .00 0. .00 XXXX2809

ATOM 2810 CA LEU A 372 -28. .747 50. .849 24. .614 1. .00 0. .00 XXXX2810

ATOM 2811 C LEU A 372 -29. .739 51. .177 23. .500 1. .00 0. .00 XXXX2811

ATOM 2812 O LEU A 372 -30. .919 50. .839 23. .588 1. .00 0. .00 XXXX2812

ATOM 2813 CB LEU A 372 -29. .497 50. .421 25. .877 1. .00 0. .00 XXXX2813

ATOM 2814 CG LEU A 372 -28. .618 49. .915 27. .023 1. .00 0. .00 XXXX2814

ATOM 2815 CD1 LEU A 372 -29. .466 49. .517 28. .220 1. .00 0. .00 XXXX2815

ATOM 2816 CD2 LEU A 372 -27. .751 48. .752 26. .563 1. .00 0. .00 XXXX2816

ATOM 2817 N LYS A 373 -29. .252 51. .842 22. .457 1. .00 0. .00 XXXX2817

ATOM 2818 CA LYS A 373 -30. .097 52. .242 21. .338 1. .00 0. .00 XXXX2818

ATOM 2819 C LYS A 373 -30. .630 51. .038 20. .571 1. .00 0. .00 XXXX2819

ATOM 2820 O LYS A 373 -31. .702 51. .102 19. .970 1. .00 0. .00 XXXX2820

ATOM 2821 CB LYS A 373 -29. .326 53. .163 20. .391 1. .00 0. .00 XXXX2821

ATOM 2822 CG LYS A 373 -28. .913 54. .485 21. .017 1. .00 0. .00 XXXX2822

ATOM 2823 CD LYS A 373 -28. .046 55. .303 20. .072 1. .00 0. .00 XXXX2823

ATOM 2824 CE LYS A 373 -27. .328 56. .422 20. .811 1. .00 0. .00 XXXX2824

ATOM 2825 NZ LYS A 373 -26. .433 57. .200 19. .911 1. .00 0. .00 XXXX2825

ATOM 2826 N GLY A 374 -29. .880 49. .941 20. .594 1. .00 0. .00 XXXX2826

ATOM 2827 CA GLY A 374 -30. .274 48. .747 19. .873 1. .00 0. .00 XXXX2827

ATOM 2828 C GLY A 374 -31. .283 47. .915 20. .638 1. .00 0. .00 XXXX2828

ATOM 2829 O GLY A 374 -31. .724 46. .868 20. .164 1. .00 0. .00 XXXX2829

ATOM 2830 N TYR A 375 -31. .653 48. .382 21. .826 1. .00 0. .00 XXXX2830

ATOM 2831 CA TYR A 375 -32. .598 47. .648 22. .657 1. .00 0. .00 XXXX2831

ATOM 2832 C TYR A 375 -33. .868 48. .458 22. .858 1. .00 0. .00 XXXX2832

ATOM 2833 O TYR A 375 -33. .907 49. .422 23. .625 1. .00 0. .00 XXXX2833

ATOM 2834 CB TYR A 375 -31. .959 47. .281 23. .993 1. .00 0. .00 XXXX2834

ATOM 2835 CG TYR A 375 -30. .748 46. .400 23. .812 1. .00 0. .00 XXXX2835

ATOM 2836 CD1 TYR A 375 -29. .484 46. .951 23. .669 1. .00 0. .00 XXXX2836

ATOM 2837 CD2 TYR A 375 -30. .872 45. .018 23. .752 1. .00 0. .00 XXXX2837

ATOM 2838 CE1 TYR A 375 -28. .374 46. .155 23. .490 1. .00 0. .00 XXXX2838

ATOM 2839 CE2 TYR A 375 -29. .766 44. .210 23. .575 1. .00 0. .00 XXXX2839

ATOM 2840 CZ TYR A 375 -28. .519 44. .786 23. .444 1. .00 0. .00 XXXX2840

ATOM 2841 OH TYR A 375 -27. .410 43. .992 23. .265 1. .00 0. .00 XXXX2841

ATOM 2842 N GLU A 376 -34. .904 48. .037 22. .143 1. .00 0. .00 XXXX2842

ATOM 2843 CA GLU A 376 -36. .183 48. .727 22. .078 1. .00 0. .00 XXXX2843

ATOM 2844 C GLU A 376 -36. .830 48. .884 23. .456 1. .00 0. .00 XXXX2844

ATOM 2845 O GLU A 376 -37. .595 49. .819 23. .689 1. .00 0. .00 XXXX2845

ATOM 2846 CB GLU A 376 -37. .099 47. .977 21. .104 1. .00 0. .00 XXXX2846

ATOM 2847 CG GLU A 376 -38. .423 48. .639 20. .804 1. .00 0. .00 XXXX2847

ATOM 2848 CD GLU A 376 -39. .496 48. .253 21. .788 1. .00 0. .00 XXXX2848

ATOM 2849 OE1 GLU A 376 -39. .319 47. .240 22. .497 1. .00 0. .00 XXXX2849 Attorney Docket No. 35327-522001 WO

ATOM 2850 OE2 GLU A 376 -40. .521 48. .955 21. .836 1. .00 0. .00 XXXX2850

ATOM 2851 N TRP A 377 -36. .520 47. .963 24. .364 1. .00 0. .00 XXXX2851

ATOM 2852 CA TRP A 377 -37. .081 47. .983 25. .712 1. .00 0. .00 XXXX2852

ATOM 2853 C TRP A 377 -36. .368 48. .959 26. .649 1. .00 0. .00 XXXX2853

ATOM 2854 O TRP A 377 -36. .816 49. .185 27. .773 1. .00 0. .00 XXXX2854

ATOM 2855 CB TRP A 377 -37. .039 46. .581 26. .322 1. .00 0. .00 XXXX2855

ATOM 2856 CG TRP A 377 -35. .684 45. .942 26. .250 1. .00 0. .00 XXXX2856

ATOM 2857 CD1 TRP A 377 -35. .259 45. .029 25. .330 1. .00 0. .00 XXXX2857

ATOM 2858 CD2 TRP A 377 -34. .568 46. .185 27. .118 1. .00 0. .00 XXXX2858

ATOM 2859 NE1 TRP A 377 -33. .954 44. .679 25. .576 1. .00 0. .00 XXXX2859

ATOM 2860 CE2 TRP A 377 -33. .507 45. .374 26. .668 1. .00 0. .00 XXXX2860

ATOM 2861 CE3 TRP A 377 -34. .366 47. .004 28. .233 1. .00 0. .00 XXXX2861

ATOM 2862 CZ2 TRP A 377 -32. .262 45. .359 27. .295 1. .00 0. .00 XXXX2862

ATOM 2863 CZ3 TRP A 377 -33. .128 46. .988 28. .853 1. .00 0. .00 XXXX2863

ATOM 2864 CH2 TRP A 377 -32. .093 46. .170 28. .382 1. .00 0. .00 XXXX2864

ATOM 2865 N ALA A 378 -35. .258 49. .530 26. .191 1. .00 0. .00 XXXX2865

ATOM 2866 CA ALA A 378 -34. .457 50. .420 27. .028 1. .00 0. .00 XXXX2866

ATOM 2867 C ALA A 378 -34. .800 51. .885 26. .776 1. .00 0. .00 XXXX2867

ATOM 2868 O ALA A 378 -34. .065 52. .783 27. .188 1. .00 0. .00 XXXX2868

ATOM 2869 CB ALA A 378 -32. .975 50. .177 26. .790 1. .00 0. .00 XXXX2869

ATOM 2870 N GLN A 379 -35. .916 52. .111 26. .089 1. .00 0. .00 XXXX2870

ATOM 2871 CA GLN A 379 -36. .325 53. .443 25. .648 1. .00 0. .00 XXXX2871

ATOM 2872 C GLN A 379 -36. .306 54. .508 26. .746 1. .00 0. .00 XXXX2872

ATOM 2873 O GLN A 379 -35. .751 55. .591 26. .560 1. .00 0. .00 XXXX2873

ATOM 2874 CB GLN A 379 -37. .726 53. .374 25. .037 1. .00 0. .00 XXXX2874

ATOM 2875 CG GLN A 379 -38. .276 54. .717 24. .587 1. .00 0. .00 XXXX2875

ATOM 2876 CD GLN A 379 -37. .534 55. .277 23. .390 1. .00 0. .00 XXXX2876

ATOM 2877 OE1 GLN A 379 -37. .283 54. .570 22. .414 1. .00 0. .00 XXXX2877

ATOM 2878 NE2 GLN A 379 -37. .180 56. .555 23. .459 1. .00 0. .00 XXXX2878

ATOM 2879 N GLY A 380 -36. .914 54. .198 27. .887 1. .00 0. .00 XXXX2879

ATOM 2880 CA GLY A 380 -37. .137 55. .189 28. .926 1. .00 0. .00 XXXX2880

ATOM 2881 C GLY A 380 -35. .979 55. .465 29. .868 1. .00 0. .00 XXXX2881

ATOM 2882 O GLY A 380 -35. .955 56. .503 30. .530 1. .00 0. .00 XXXX2882

ATOM 2883 N LEU A 381 -35. .023 54. .543 29. .932 1. .00 0. .00 XXXX2883

ATOM 2884 CA LEU A 381 -33. .905 54. .648 30. .869 1. .00 0. .00 XXXX2884

ATOM 2885 C LEU A 381 -33. .132 55. .956 30. .717 1. .00 0. .00 XXXX2885

ATOM 2886 O LEU A 381 -32. .478 56. .191 29. .702 1. .00 0. .00 XXXX2886

ATOM 2887 CB LEU A 381 -32. .958 53. .461 30. .690 1. .00 0. .00 XXXX2887

ATOM 2888 CG LEU A 381 -33. .601 52. .083 30. .854 1. .00 0. .00 XXXX2888

ATOM 2889 CD1 LEU A 381 -32. .588 50. .978 30. .596 1. .00 0. .00 XXXX2889

ATOM 2890 CD2 LEU A 381 -34. .218 51. .943 32. .239 1. .00 0. .00 XXXX2890

ATOM 2899 N ILE B 15 -6. .934 63. .095 62. .651 1. .00 0. .00 XXXX2899

ATOM 2900 CA ILE B 15 -5. .481 63. .191 62. .749 1. .00 0. .00 XXXX2900

ATOM 2901 C ILE B 15 -4. .856 62. .631 61. .479 1. .00 0. .00 XXXX2901

ATOM 2902 O ILE B 15 -4. .893 61. .425 61. .238 1. .00 0. .00 XXXX2902

ATOM 2903 CB ILE B 15 -4. .922 62. .432 63. .964 1. .00 0. .00 XXXX2903

ATOM 2904 CGI ILE B 15 -5. .376 63. .089 65. .268 1. .00 0. .00 XXXX2904

ATOM 2905 CG2 ILE B 15 -3. .402 62. .391 63. .907 1. .00 0. .00 XXXX2905

ATOM 2906 CD1 ILE B 15 -5. .033 62. .282 66. .501 1. .00 0. .00 XXXX2906

ATOM 2907 N LYS B 16 -4. .284 63. .514 60. .669 1. .00 0. .00 XXXX2907

ATOM 2908 CA LYS B 16 -3. .730 63. .112 59. .385 1. .00 0. .00 XXXX2908

ATOM 2909 C LYS B 16 -2. .339 62. .513 59. .550 1. .00 0. .00 XXXX2909

ATOM 2910 O LYS B 16 -1. .503 63. .048 60. .278 1. .00 0. .00 XXXX2910

ATOM 2911 CB LYS B 16 -3. .687 64. .307 58. .432 1. .00 0. .00 XXXX2911

ATOM 2912 CG LYS B 16 -5. .066 64. .799 58. .019 1. .00 0. .00 XXXX2912

ATOM 2913 CD LYS B 16 -4. .985 65. .928 57. .007 1. .00 0. .00 XXXX2913

ATOM 2914 CE LYS B 16 -6. .374 66. .343 56. .545 1. .00 0. .00 XXXX2914

ATOM 2915 NZ LYS B 16 -6. .325 67. .397 55. .496 1. .00 0. .00 XXXX2915

ATOM 2916 N VAL B 17 -2. .098 61. .397 58. .872 1. .00 0. .00 XXXX2916

ATOM 2917 CA VAL B 17 -0. .788 60. .761 58. .891 1. .00 0. .00 XXXX2917

ATOM 2918 C VAL B 17 -0. .320 60. .505 57. .466 1. .00 0. .00 XXXX2918

ATOM 2919 O VAL B 17 -1. .114 60. .151 56. .594 1. .00 0. .00 XXXX2919

ATOM 2920 CB VAL B 17 -0. .801 59. .433 59. .676 1. .00 0. .00 XXXX2920

ATOM 2921 CGI VAL B 17 -1. .248 59. .663 61. .112 1. .00 0. .00 XXXX2921

ATOM 2922 CG2 VAL B 17 -1. .696 58. .417 58. .988 1. .00 0. .00 XXXX2922

ATOM 2923 N GLY B 18 0. .971 60. .691 57. .230 1. .00 0. .00 XXXX2923

ATOM 2924 CA GLY B 18 1. .517 60. .513 55. .901 1. .00 0. .00 XXXX2924 Attorney Docket No. 35327-522001 WO

ATOM 2925 C GLY B 18 2. .021 59. .109 55. .643 1. .00 0. .00 XXXX2925

ATOM 2926 O GLY B 18 2. .592 58. .467 56. .524 1. .00 0. .00 XXXX2926

ATOM 2927 N ILE B 19 1. .795 58. .631 54. .424 1. .00 0. .00 XXXX2927

ATOM 2928 CA ILE B 19 2. .393 57. .388 53. .960 1. .00 0. .00 XXXX2928

ATOM 2929 C ILE B 19 3. .189 57. .690 52. .698 1. .00 0. .00 XXXX2929

ATOM 2930 O ILE B 19 2. .624 58. .088 51. .680 1. .00 0. .00 XXXX2930

ATOM 2931 CB ILE B 19 1. .336 56. .304 53. .680 1. .00 0. .00 XXXX2931

ATOM 2932 CGI ILE B 19 0. .684 55. .850 54. .988 1. .00 0. .00 XXXX2932

ATOM 2933 CG2 ILE B 19 1. .966 55. .120 52. .960 1. .00 0. .00 XXXX2933

ATOM 2934 CD1 ILE B 19 -0. .410 54. .816 54. .804 1. .00 0. .00 XXXX2934

ATOM 2935 N LEU B 20 4. .501 57. .501 52. .767 1. .00 0. .00 XXXX2935

ATOM 2936 CA LEU B 20 5. .383 57. .924 51. .689 1. .00 0. .00 XXXX2936

ATOM 2937 C LEU B 20 6. .295 56. .784 51. .246 1. .00 0. .00 XXXX2937

ATOM 2938 O LEU B 20 7. .319 56. .508 51. .871 1. .00 0. .00 XXXX2938

ATOM 2939 CB LEU B 20 6. .207 59. .135 52. .135 1. .00 0. .00 XXXX2939

ATOM 2940 CG LEU B 20 7. .245 59. .684 51. .157 1. .00 0. .00 XXXX2940

ATOM 2941 CD1 LEU B 20 6. .599 60. .023 49. .823 1. .00 0. .00 XXXX2941

ATOM 2942 CD2 LEU B 20 7. .948 60. .897 51. .750 1. .00 0. .00 XXXX2942

ATOM 2943 N HIS B 21 5. .912 56. .123 50. .159 1. .00 0. .00 XXXX2943

ATOM 2944 CA HIS B 21 6. .633 54. .954 49. .678 1. .00 0. .00 XXXX2944

ATOM 2945 C HIS B 21 6. .710 54. .946 48. .160 1. .00 0. .00 XXXX2945

ATOM 2946 O HIS B 21 5. .942 55. .635 47. .488 1. .00 0. .00 XXXX2946

ATOM 2947 CB HIS B 21 5. .959 53. .671 50. .170 1. .00 0. .00 XXXX2947

ATOM 2948 CG HIS B 21 6. .241 53. .349 51. .606 1. .00 0. .00 XXXX2948

ATOM 2949 ND1 HIS B 21 7. .499 53. .014 52. .057 1. .00 0. .00 XXXX2949

ATOM 2950 CD2 HIS B 21 5. .428 53. .309 52. .686 1. .00 0. .00 XXXX2950

ATOM 2951 CE1 HIS B 21 7. .448 52. .782 53. .358 1. .00 0. .00 XXXX2951

ATOM 2952 NE2 HIS B 21 6. .205 52. .954 53. .764 1. .00 0. .00 XXXX2952

ATOM 2953 N SER B 22 7. .643 54. .169 47. .623 1. .00 0. .00 XXXX2953

ATOM 2954 CA SER B 22 7. .728 53. .974 46. .183 1. .00 0. .00 XXXX2954

ATOM 2955 C SER B 22 6. .604 53. .061 45. .711 1. .00 0. .00 XXXX2955

ATOM 2956 O SER B 22 6. .669 51. .843 45. .884 1. .00 0. .00 XXXX2956

ATOM 2957 CB SER B 22 9. .083 53. .382 45. .794 1. .00 0. .00 XXXX2957

ATOM 2958 OG SER B 22 10. .148 54. .213 46. .222 1. .00 0. .00 XXXX2958

ATOM 2959 N LEU B 23 5. .568 53. .654 45. .126 1. .00 0. .00 XXXX2959

ATOM 2960 CA LEU B 23 4. .466 52. .882 44. .563 1. .00 0. .00 XXXX2960

ATOM 2961 C LEU B 23 4. .692 52. .676 43. .071 1. .00 0. .00 XXXX2961

ATOM 2962 O LEU B 23 3. .946 51. .955 42. .409 1. .00 0. .00 XXXX2962

ATOM 2963 CB LEU B 23 3. .127 53. .575 44. .823 1. .00 0. .00 XXXX2963

ATOM 2964 CG LEU B 23 2. .910 54. .014 46. .275 1. .00 0. .00 XXXX2964

ATOM 2965 CD1 LEU B 23 1. .545 54. .661 46. .453 1. .00 0. .00 XXXX2965

ATOM 2966 CD2 LEU B 23 3. .086 52. .836 47. .227 1. .00 0. .00 XXXX2966

ATOM 2967 N SER B 24 5. .729 53. .326 42. .553 1. .00 0. .00 XXXX2967

ATOM 2968 CA SER B 24 6. .172 53. .127 41. .179 1. .00 0. .00 XXXX2968

ATOM 2969 C SER B 24 7. .696 53. .111 41. .138 1. .00 0. .00 XXXX2969

ATOM 2970 O SER B 24 8. .352 53. .569 42. .073 1. .00 0. .00 XXXX2970

ATOM 2971 CB SER B 24 5. .617 54. .220 40. .259 1. .00 0. .00 XXXX2971

ATOM 2972 OG SER B 24 6. .102 55. .501 40. .630 1. .00 0. .00 XXXX2972

ATOM 2973 N GLY B 25 8. .259 52. .589 40. .053 1. .00 0. .00 XXXX2973

ATOM 2974 CA GLY B 25 9. .701 52. .541 39. .905 1. .00 0. .00 XXXX2974

ATOM 2975 C GLY B 25 10. .336 51. .277 40. .454 1. .00 0. .00 XXXX2975

ATOM 2976 O GLY B 25 9. .648 50. .366 40. .911 1. .00 0. .00 XXXX2976

ATOM 2977 N THR B 26 11. .664 51. .233 40. .408 1. .00 0. .00 XXXX2977

ATOM 2978 CA THR B 26 12. .427 50. .030 40. .733 1. .00 0. .00 XXXX2978

ATOM 2979 C THR B 26 12. .247 49. .528 42. .168 1. .00 0. .00 XXXX2979

ATOM 2980 O THR B 26 12. .488 48. .354 42. .447 1. .00 0. .00 XXXX2980

ATOM 2981 CB THR B 26 13. .931 50. .260 40. .492 1. .00 0. .00 XXXX2981

ATOM 2982 OG1 THR B 26 14. .639 49. .026 40. .653 1. .00 0. .00 XXXX2982

ATOM 2983 CG2 THR B 26 14. .478 51. .289 41. .471 1. .00 0. .00 XXXX2983

ATOM 2984 N MET B 27 11. .832 50. .407 43. .074 1. .00 0. .00 XXXX2984

ATOM 2985 CA MET B 27 11. .682 50. .029 44. .480 1. .00 0. .00 XXXX2985

ATOM 2986 C MET B 27 10. .265 49. .596 44. .852 1. .00 0. .00 XXXX2986

ATOM 2987 O MET B 27 10. .024 49. .162 45. .981 1. .00 0. .00 XXXX2987

ATOM 2988 CB MET B 27 12. .110 51. .186 45. .388 1. .00 0. .00 XXXX2988

ATOM 2989 CG MET B 27 13. .603 51. .486 45. .381 1. .00 0. .00 XXXX2989

ATOM 2990 SD MET B 27 14. .614 50. .050 45. .796 1. .00 0. .00 XXXX2990

ATOM 2991 CE MET B 27 13. .877 49. .555 47. .351 1. .00 0. .00 XXXX2991 Attorney Docket No. 35327-522001 WO

ATOM 2992 N SER B 28 9. .334 49. .706 43. .908 1. .00 0. .00 XXXX2992

ATOM 2993 CA SER B 28 7. .927 49. .424 44. .192 1. .00 0. .00 XXXX2993

ATOM 2994 C SER B 28 7. .695 47. .954 44. .533 1. .00 0. .00 XXXX2994

ATOM 2995 O SER B 28 6. .741 47. .615 45. .233 1. .00 0. .00 XXXX2995

ATOM 2996 CB SER B 28 7. .048 49. .828 43. .005 1. .00 0. .00 XXXX2996

ATOM 2997 OG SER B 28 7. .305 49. .012 41. .874 1. .00 0. .00 XXXX2997

ATOM 2998 N ILE B 29 8. .571 47. .085 44. .039 1. .00 0. .00 XXXX2998

ATOM 2999 CA ILE B 29 8. .506 45. .665 44. .368 1. .00 0. .00 XXXX2999

ATOM 3000 C ILE B 29 8. .567 45. .467 45. .880 1. .00 0. .00 XXXX3000

ATOM 3001 O ILE B 29 7. .973 44. .535 46. .425 1. .00 0. .00 XXXX3001

ATOM 3002 CB ILE B 29 9. .649 44. .873 43. .703 1. .00 0. .00 XXXX3002

ATOM 3003 CGI ILE B 29 9. .535 43. .384 44. .038 1. .00 0. .00 XXXX3003

ATOM 3004 CD1 ILE B 29 10. .551 42. .517 43. .325 1. .00 0. .00 XXXX3004

ATOM 3005 CG2 ILE B 29 11. .003 45. .422 44. .136 1. .00 0. .00 XXXX3005

ATOM 3006 N SER B 30 9. .289 46. .361 46. .547 1. .00 0. .00 XXXX3006

ATOM 3007 CA SER B 30 9. .529 46. .253 47. .980 1. .00 0. .00 XXXX3007

ATOM 3008 C SER B 30 8. .563 47. .087 48. .821 1. .00 0. .00 XXXX3008

ATOM 3009 O SER B 30 8. .104 46. .637 49. .870 1. .00 0. .00 XXXX3009

ATOM 3010 CB SER B 30 10. .970 46. .666 48. .301 1. .00 0. .00 XXXX3010

ATOM 3011 OG SER B 30 11. .897 45. .673 47. .895 1. .00 0. .00 XXXX3011

ATOM 3012 N GLU B 31 8. .252 48. .296 48. .363 1. .00 0. .00 XXXX3012

ATOM 3013 CA GLU B 31 7. .616 49. .286 49. .232 1. .00 0. .00 XXXX3013

ATOM 3014 C GLU B 31 6. .086 49. .296 49. .214 1. .00 0. .00 XXXX3014

ATOM 3015 O GLU B 31 5. .465 49. .802 50. .149 1. .00 0. .00 XXXX3015

ATOM 3016 CB GLU B 31 8. .119 50. .688 48. .882 1. .00 0. .00 XXXX3016

ATOM 3017 CG GLU B 31 9. .597 50. .912 49. .165 1. .00 0. .00 XXXX3017

ATOM 3018 CD GLU B 31 9. .976 52. .377 49. .106 1. .00 0. .00 XXXX3018

ATOM 3019 OE1 GLU B 31 9. .323 53. .185 49. .800 1. .00 0. .00 XXXX3019

ATOM 3020 OE2 GLU B 31 10. .925 52. .724 48. .373 1. .00 0. .00 XXXX3020

ATOM 3021 N VAL B 32 5. .476 48. .756 48. .164 1. .00 0. .00 XXXX3021

ATOM 3022 CA VAL B 32 4. .018 48. .773 48. .073 1. .00 0. .00 XXXX3022

ATOM 3023 C VAL B 32 3. .397 48. .026 49. .248 1. .00 0. .00 XXXX3023

ATOM 3024 O VAL B 32 2. .392 48. .464 49. .810 1. .00 0. .00 XXXX3024

ATOM 3025 CB VAL B 32 3. .514 48. .161 46. .755 1. .00 0. .00 XXXX3025

ATOM 3026 CGI VAL B 32 2. .015 47. .890 46. .836 1. .00 0. .00 XXXX3026

ATOM 3027 CG2 VAL B 32 3. .830 49. .088 45. .590 1. .00 0. .00 XXXX3027

ATOM 3028 N SER B 33 4. .007 46. .904 49. .620 1. .00 0. .00 XXXX3028

ATOM 3029 CA SER B 33 3. .506 46. .087 50. .721 1. .00 0. .00 XXXX3029

ATOM 3030 C SER B 33 3. .689 46. .775 52. .074 1. .00 0. .00 XXXX3030

ATOM 3031 O SER B 33 2. .996 46. .449 53. .039 1. .00 0. .00 XXXX3031

ATOM 3032 CB SER B 33 4. .195 44. .721 50. .730 1. .00 0. .00 XXXX3032

ATOM 3033 OG SER B 33 5. .600 44. .855 50. .859 1. .00 0. .00 XXXX3033

ATOM 3034 N LEU B 34 4. .616 47. .727 52. .144 1. .00 0. .00 XXXX3034

ATOM 3035 CA LEU B 34 4. .786 48. .523 53. .355 1. .00 0. .00 XXXX3035

ATOM 3036 C LEU B 34 3. .610 49. .474 53. .526 1. .00 0. .00 XXXX3036

ATOM 3037 O LEU B 34 3. .131 49. .687 54. .640 1. .00 0. .00 XXXX3037

ATOM 3038 CB LEU B 34 6. .100 49. .306 53. .328 1. .00 0. .00 XXXX3038

ATOM 3039 CG LEU B 34 7. .388 48. .485 53. .284 1. .00 0. .00 XXXX3039

ATOM 3040 CD1 LEU B 34 7. .287 47. .288 54. .213 1. .00 0. .00 XXXX3040

ATOM 3041 CD2 LEU B 34 8. .576 49. .359 53. .661 1. .00 0. .00 XXXX3041

ATOM 3042 N LYS B 35 3. .157 50. .051 52. .417 1. .00 0. .00 XXXX3042

ATOM 3043 CA LYS B 35 1. .946 50. .863 52. .417 1. .00 0. .00 XXXX3043

ATOM 3044 C LYS B 35 0. .760 50. .041 52. .916 1. .00 0. .00 XXXX3044

ATOM 3045 O LYS B 35 -0. .058 50. .527 53. .695 1. .00 0. .00 XXXX3045

ATOM 3046 CB LYS B 35 1. .657 51. .413 51. .018 1. .00 0. .00 XXXX3046

ATOM 3047 CG LYS B 35 0. .312 52. .113 50. .894 1. .00 0. .00 XXXX3047

ATOM 3048 CD LYS B 35 -0. .269 51. .942 49. .500 1. .00 0. .00 XXXX3048

ATOM 3049 CE LYS B 35 -0. .580 50. .483 49. .216 1. .00 0. .00 XXXX3049

ATOM 3050 NZ LYS B 35 -1. .406 50. .319 47. .989 1. .00 0. .00 XXXX3050

ATOM 3051 N ASP B 36 0. .678 48. .794 52. .457 1. .00 0. .00 XXXX3051

ATOM 3052 CA ASP B 36 -0. .389 47. .882 52. .864 1. .00 0. .00 XXXX3052

ATOM 3053 C ASP B 36 -0. .330 47. .587 54. .360 1. .00 0. .00 XXXX3053

ATOM 3054 O ASP B 36 -1. .355 47. .572 55. .043 1. .00 0. .00 XXXX3054

ATOM 3055 CB ASP B 36 -0. .308 46. .570 52. .079 1. .00 0. .00 XXXX3055

ATOM 3056 CG ASP B 36 -0. .647 46. .742 50. .610 1. .00 0. .00 XXXX3056

ATOM 3057 OD1 ASP B 36 -1. .333 47. .727 50. .264 1. .00 0. .00 XXXX3057

ATOM 3058 OD2 ASP B 36 -0. .229 45. .886 49. .801 1. .00 0. .00 XXXX3058 Attorney Docket No. 35327-522001 WO

ATOM 3059 N ALA B 37 0. .879 47. .353 54. .862 1. .00 0. .00 XXXX3059

ATOM 3060 CA ALA B 37 1. .080 47. .054 56. .276 1. .00 0. .00 XXXX3060

ATOM 3061 C ALA B 37 0. .661 48. .226 57. .157 1. .00 0. .00 XXXX3061

ATOM 3062 O ALA B 37 -0. .002 48. .041 58. .177 1. .00 0. .00 XXXX3062

ATOM 3063 CB ALA B 37 2. .533 46. .689 56. .538 1. .00 0. .00 XXXX3063

ATOM 3064 N GLU B 38 1. .057 49. .430 56. .761 1. .00 0. .00 XXXX3064

ATOM 3065 CA GLU B 38 0. .739 50. .630 57. .527 1. .00 0. .00 XXXX3065

ATOM 3066 C GLU B 38 -0. .760 50. .917 57. .526 1. .00 0. .00 XXXX3066

ATOM 3067 O GLU B 38 -1. .323 51. .331 58. .540 1. .00 0. .00 XXXX3067

ATOM 3068 CB GLU B 38 1. .507 51. .833 56. .978 1. .00 0. .00 XXXX3068

ATOM 3069 CG GLU B 38 3. .015 51. .739 57. .166 1. .00 0. .00 XXXX3069

ATOM 3070 CD GLU B 38 3. .787 52. .455 56. .075 1. .00 0. .00 XXXX3070

ATOM 3071 OE1 GLU B 38 3. .145 53. .033 55. .174 1. .00 0. .00 XXXX3071

ATOM 3072 OE2 GLU B 38 5. .036 52. .442 56. .120 1. .00 0. .00 XXXX3072

ATOM 3073 N LEU B 39 -1. .407 50. .692 56. .387 1. .00 0. .00 XXXX3073

ATOM 3074 CA LEU B 39 -2. .841 50. .939 56. .273 1. .00 0. .00 XXXX3074

ATOM 3075 C LEU B 39 -3. .650 49. .961 57. .119 1. .00 0. .00 XXXX3075

ATOM 3076 O LEU B 39 -4. .701 50. .316 57. .653 1. .00 0. .00 XXXX3076

ATOM 3077 CB LEU B 39 -3. .285 50. .859 54. .812 1. .00 0. .00 XXXX3077

ATOM 3078 CG LEU B 39 -2. .901 52. .043 53. .922 1. .00 0. .00 XXXX3078

ATOM 3079 CD1 LEU B 39 -3. .270 51. .771 52. .470 1. .00 0. .00 XXXX3079

ATOM 3080 CD2 LEU B 39 -3. .562 53. .321 54. .418 1. .00 0. .00 XXXX3080

ATOM 3081 N MET B 40 -3. .161 48. .730 57. .237 1. .00 0. .00 XXXX3081

ATOM 3082 CA MET B 40 -3. .824 47. .727 58. .063 1. .00 0. .00 XXXX3082

ATOM 3083 C MET B 40 -3. .760 48. .120 59. .535 1. .00 0. .00 XXXX3083

ATOM 3084 O MET B 40 -4. .758 48. .043 60. .252 1. .00 0. .00 XXXX3084

ATOM 3085 CB MET B 40 -3. .201 46. .347 57. .856 1. .00 0. .00 XXXX3085

ATOM 3086 CG MET B 40 -3. .923 45. .242 58. .611 1. .00 0. .00 XXXX3086

ATOM 3087 SD MET B 40 -3. .281 43. .595 58. .269 1. .00 0. .00 XXXX3087

ATOM 3088 CE MET B 40 -1. .684 43. .687 59. .071 1. .00 0. .00 XXXX3088

ATOM 3089 N ALA B 41 -2. .576 48. .530 59. .981 1. .00 0. .00 XXXX3089

ATOM 3090 CA ALA B 41 -2. .390 48. .986 61. .353 1. .00 0. .00 XXXX3090

ATOM 3091 C ALA B 41 -3. .297 50. .176 61. .650 1. .00 0. .00 XXXX3091

ATOM 3092 O ALA B 41 -3. .935 50. .238 62. .701 1. .00 0. .00 XXXX3092

ATOM 3093 CB ALA B 41 -0. .933 49. .349 61. .600 1. .00 0. .00 XXXX3093

ATOM 3094 N ILE B 42 -3. .347 51. .118 60. .712 1. .00 0. .00 XXXX3094

ATOM 3095 CA ILE B 42 -4. .214 52. .284 60. .832 1. .00 0. .00 XXXX3095

ATOM 3096 C ILE B 42 -5. .686 51. .889 60. .920 1. .00 0. .00 XXXX3096

ATOM 3097 O ILE B 42 -6. .435 52. .436 61. .729 1. .00 0. .00 XXXX3097

ATOM 3098 CB ILE B 42 -4. .022 53. .249 59. .650 1. .00 0. .00 XXXX3098

ATOM 3099 CGI ILE B 42 -2. .639 53. .904 59. .719 1. .00 0. .00 XXXX3099

ATOM 3100 CD1 ILE B 42 -2. .271 54. .684 58. .476 1. .00 0. .00 XXXX3100

ATOM 3101 CG2 ILE B 42 -5. .116 54. .306 59. .645 1. .00 0. .00 XXXX3101

ATOM 3102 N GLU B 43 -6. .100 50. .942 60. .084 1. .00 0. .00 XXXX3102

ATOM 3103 CA GLU B 43 -7. .484 50. .478 60. .096 1. .00 0. .00 XXXX3103

ATOM 3104 C GLU B 43 -7. .824 49. .823 61. .429 1. .00 0. .00 XXXX3104

ATOM 3105 O GLU B 43 -8. .913 50. .023 61. .971 1. .00 0. .00 XXXX3105

ATOM 3106 CB GLU B 43 -7. .742 49. .498 58. .950 1. .00 0. .00 XXXX3106

ATOM 3107 CG GLU B 43 -9. .146 48. .906 58. .958 1. .00 0. .00 XXXX3107

ATOM 3108 CD GLU B 43 -9. .402 47. .980 57. .784 1. .00 0. .00 XXXX3108

ATOM 3109 OE1 GLU B 43 -8. .695 46. .957 57. .663 1. .00 0. .00 XXXX3109

ATOM 3110 OE2 GLU B 43 -10. .314 48. .275 56. .983 1. .00 0. .00 XXXX3110

ATOM 3111 N GLU B 44 -6. .890 49. .032 61. .948 1. .00 0. .00 XXXX3111

ATOM 3112 CA GLU B 44 -7. .076 48. .361 63. .230 1. .00 0. .00 XXXX3112

ATOM 3113 C GLU B 44 -7. .241 49. .366 64. .365 1. .00 0. .00 XXXX3113

ATOM 3114 O GLU B 44 -8. .156 49. .250 65. .181 1. .00 0. .00 XXXX3114

ATOM 3115 CB GLU B 44 -5. .900 47. .425 63. .524 1. .00 0. .00 XXXX3115

ATOM 3116 CG GLU B 44 -5. .817 46. .225 62. .595 1. .00 0. .00 XXXX3116

ATOM 3117 CD GLU B 44 -4. .617 45. .344 62. .885 1. .00 0. .00 XXXX3117

ATOM 3118 OE1 GLU B 44 -3. .835 45. .685 63. .796 1. .00 0. .00 XXXX3118

ATOM 3119 OE2 GLU B 44 -4. .455 44. .313 62. .200 1. .00 0. .00 XXXX3119

ATOM 3120 N ILE B 45 -6. .349 50. .350 64. .409 1. .00 0. .00 XXXX3120

ATOM 3121 CA ILE B 45 -6. .390 51. .381 65. .439 1. .00 0. .00 XXXX3121

ATOM 3122 C ILE B 45 -7. .672 52. .212 65. .364 1. .00 0. .00 XXXX3122

ATOM 3123 O ILE B 45 -8. .257 52. .551 66. .392 1. .00 0. .00 XXXX3123

ATOM 3124 CB ILE B 45 -5. .168 52. .313 65. .342 1. .00 0. .00 XXXX3124

ATOM 3125 CGI ILE B 45 -3. .891 51. .545 65. .700 1. .00 0. .00 XXXX3125 Attorney Docket No. 35327-522001 WO

ATOM 3126 CD1 ILE B 45 -2. .613 52. .292 65. .379 1. .00 0. .00 XXXX3126

ATOM 3127 CG2 ILE B 45 -5. .345 53. .522 66. .248 1. .00 0. .00 XXXX3127

ATOM 3128 N ASN B 46 -8. .105 52. .539 64. .150 1. .00 0. .00 XXXX3128

ATOM 3129 CA ASN B 46 -9. .337 53. .300 63. .964 1. .00 0. .00 XXXX3129

ATOM 3130 C ASN B 46 -10. .568 52. .530 64. .433 1. .00 0. .00 XXXX3130

ATOM 3131 O ASN B 46 -11. .484 53. .105 65. .021 1. .00 0. .00 XXXX3131

ATOM 3132 CB ASN B 46 -9. .508 53. .702 62. .497 1. .00 0. .00 XXXX3132

ATOM 3133 CG ASN B 46 -8. .645 54. .890 62. .112 1. .00 0. .00 XXXX3133

ATOM 3134 OD1 ASN B 46 -8. .218 55. .664 62. .968 1. .00 0. .00 XXXX3134

ATOM 3135 ND2 ASN B 46 -8. .387 55. .041 60. .817 1. .00 0. .00 XXXX3135

ATOM 3136 N ASN B 47 -10. .583 51. .228 64. .170 1. .00 0. .00 XXXX3136

ATOM 3137 CA ASN B 47 -11. .700 50. .385 64. .578 1. .00 0. .00 XXXX3137

ATOM 3138 C ASN B 47 -11. .779 50. .208 66. .092 1. .00 0. .00 XXXX3138

ATOM 3139 O ASN B 47 -12. .835 49. .871 66. .626 1. .00 0. .00 XXXX3139

ATOM 3140 CB ASN B 47 -11. .609 49. .017 63. .897 1. .00 0. .00 XXXX3140

ATOM 3141 CG ASN B 47 -11. .884 49. .090 62. .408 1. .00 0. .00 XXXX3141

ATOM 3142 OD1 ASN B 47 -12. .461 50. .061 61. .918 1. .00 0. .00 XXXX3142

ATOM 3143 ND2 ASN B 47 -11. .472 48. .059 61. .679 1. .00 0. .00 XXXX3143

ATOM 3144 N ASN B 48 -10. .663 50. .435 66. .778 1. .00 0. .00 XXXX3144

ATOM 3145 CA ASN B 48 -10. .632 50. .351 68. .237 1. .00 0. .00 XXXX3145

ATOM 3146 C ASN B 48 -10. .850 51. .701 68. .913 1. .00 0. .00 XXXX3146

ATOM 3147 O ASN B 48 -10. .627 51. .842 70. .115 1. .00 0. .00 XXXX3147

ATOM 3148 CB ASN B 48 -9. .309 49. .745 68. .713 1. .00 0. .00 XXXX3148

ATOM 3149 CG ASN B 48 -9. .218 48. .257 68. .440 1. .00 0. .00 XXXX3149

ATOM 3150 OD1 ASN B 48 -10. .178 47. .640 67. .978 1. .00 0. .00 XXXX3150

ATOM 3151 ND2 ASN B 48 -8. .063 47. .670 68. .735 1. .00 0. .00 XXXX3151

ATOM 3152 N GLY B 49 -11. .289 52. .690 68. .142 1. .00 0. .00 XXXX3152

ATOM 3153 CA GLY B 49 -11. .579 54. .003 68. .690 1. .00 0. .00 XXXX3153

ATOM 3154 C GLY B 49 -10. .520 55. .054 68. .413 1. .00 0. .00 XXXX3154

ATOM 3155 O GLY B 49 -10. .577 56. .158 68. .954 1. .00 0. .00 XXXX3155

ATOM 3156 N GLY B 50 -9. .553 54. .717 67. .567 1. .00 0. .00 XXXX3156

ATOM 3157 CA GLY B 50 -8. .566 55. .681 67. .113 1. .00 0. .00 XXXX3157

ATOM 3158 C GLY B 50 -7. .608 56. .193 68. .173 1. .00 0. .00 XXXX3158

ATOM 3159 O GLY B 50 -7. .261 55. .478 69. .114 1. .00 0. .00 XXXX3159

ATOM 3160 N VAL B 51 -7. .179 57. .443 68. .013 1. .00 0. .00 XXXX3160

ATOM 3161 CA VAL B 51 -6. .139 58. .026 68. .855 1. .00 0. .00 XXXX3161

ATOM 3162 C VAL B 51 -6. .572 59. .380 69. .407 1. .00 0. .00 XXXX3162

ATOM 3163 O VAL B 51 -6. .934 60. .279 68. .650 1. .00 0. .00 XXXX3163

ATOM 3164 CB VAL B 51 -4. .818 58. .197 68. .079 1. .00 0. .00 XXXX3164

ATOM 3165 CGI VAL B 51 -3. .811 58. .976 68. .911 1. .00 0. .00 XXXX3165

ATOM 3166 CG2 VAL B 51 -4. .257 56. .843 67. .682 1. .00 0. .00 XXXX3166

ATOM 3167 N LEU B 52 -6. .518 59. .516 70. .730 1. .00 0. .00 XXXX3167

ATOM 3168 CA LEU B 52 -6. .982 60. .721 71. .412 1. .00 0. .00 XXXX3168

ATOM 3169 C LEU B 52 -8. .408 61. .078 70. .999 1. .00 0. .00 XXXX3169

ATOM 3170 O LEU B 52 -8. .753 62. .252 70. .872 1. .00 0. .00 XXXX3170

ATOM 3171 CB LEU B 52 -6. .045 61. .901 71. .131 1. .00 0. .00 XXXX3171

ATOM 3172 CG LEU B 52 -4. .582 61. .766 71. .562 1. .00 0. .00 XXXX3172

ATOM 3173 CD1 LEU B 52 -3. .815 63. .039 71. .233 1. .00 0. .00 XXXX3173

ATOM 3174 CD2 LEU B 52 -4. .475 61. .446 73. .046 1. .00 0. .00 XXXX3174

ATOM 3175 N GLY B 53 -9. .234 60. .056 70. .794 1. .00 0. .00 XXXX3175

ATOM 3176 CA GLY B 53 -10. .622 60. .257 70. .420 1. .00 0. .00 XXXX3176

ATOM 3177 C GLY B 53 -10. .813 60. .660 68. .969 1. .00 0. .00 XXXX3177

ATOM 3178 O GLY B 53 -11. .910 61. .044 68. .565 1. .00 0. .00 XXXX3178

ATOM 3179 N LYS B 54 -9. .748 60. .562 68. .179 1. .00 0. .00 XXXX3179

ATOM 3180 CA LYS B 54 -9. .816 60. .902 66. .761 1. .00 0. .00 XXXX3180

ATOM 3181 C LYS B 54 -9. .420 59. .716 65. .890 1. .00 0. .00 XXXX3181

ATOM 3182 O LYS B 54 -8. .609 58. .883 66. .293 1. .00 0. .00 XXXX3182

ATOM 3183 CB LYS B 54 -8. .908 62. .095 66. .446 1. .00 0. .00 XXXX3183

ATOM 3184 CG LYS B 54 -9. .235 63. .372 67. .201 1. .00 0. .00 XXXX3184

ATOM 3185 CD LYS B 54 -8. .211 64. .453 66. .885 1. .00 0. .00 XXXX3185

ATOM 3186 CE LYS B 54 -8. .517 65. .756 67. .606 1. .00 0. .00 XXXX3186

ATOM 3187 NZ LYS B 54 -9. .781 66. .379 67. .130 1. .00 0. .00 XXXX3187

ATOM 3188 N LYS B 55 -9. .994 59. .643 64. .694 1. .00 0. .00 XXXX3188

ATOM 3189 CA LYS B 55 -9. .595 58. .629 63. .725 1. .00 0. .00 XXXX3189

ATOM 3190 C LYS B 55 -8. .370 59. .094 62. .952 1. .00 0. .00 XXXX3190

ATOM 3191 O LYS B 55 -8. .167 60. .292 62. .757 1. .00 0. .00 XXXX3191

ATOM 3192 CB LYS B 55 -10. .741 58. .310 62. .763 1. .00 0. .00 XXXX3192 Attorney Docket No. 35327-522001 WO

ATOM 3193 CG LYS B 55 -11. .954 57. .678 63. .429 1. .00 0. .00 XXXX3193

ATOM 3194 CD LYS B 55 -11. .535 56. .552 64. .363 1. .00 0. .00 XXXX3194

ATOM 3195 CE LYS B 55 -12. .735 55. .922 65. .046 1. .00 0. .00 XXXX3195

ATOM 3196 NZ LYS B 55 -13. .631 55. .247 64. .066 1. .00 0. .00 XXXX3196

ATOM 3197 N LEU B 56 -7. .555 58. .142 62. .512 1. .00 0. .00 XXXX3197

ATOM 3198 CA LEU B 56 -6. .387 58. .457 61. .701 1. .00 0. .00 XXXX3198

ATOM 3199 C LEU B 56 -6. .762 58. .515 60. .225 1. .00 0. .00 XXXX3199

ATOM 3200 O LEU B 56 -7. .447 57. .628 59. .717 1. .00 0. .00 XXXX3200

ATOM 3201 CB LEU B 56 -5. .284 57. .423 61. .930 1. .00 0. .00 XXXX3201

ATOM 3202 CG LEU B 56 -4. .871 57. .206 63. .388 1. .00 0. .00 XXXX3202

ATOM 3203 CD1 LEU B 56 -3. .931 56. .015 63. .509 1. .00 0. .00 XXXX3203

ATOM 3204 CD2 LEU B 56 -4. .236 58. .463 63. .967 1. .00 0. .00 XXXX3204

ATOM 3205 N GLU B 57 -6. .313 59. .564 59. .544 1. .00 0. .00 XXXX3205

ATOM 3206 CA GLU B 57 -6. .571 59. .720 58. .116 1. .00 0. .00 XXXX3206

ATOM 3207 C GLU B 57 -5. .266 59. .688 57. .334 1. .00 0. .00 XXXX3207

ATOM 3208 O GLU B 57 -4. .501 60. .651 57. .356 1. .00 0. .00 XXXX3208

ATOM 3209 CB GLU B 57 -7. .317 61. .027 57. .837 1. .00 0. .00 XXXX3209

ATOM 3210 CG GLU B 57 -7. .524 61. .313 56. .358 1. .00 0. .00 XXXX3210

ATOM 3211 CD GLU B 57 -8. .311 62. .585 56. .113 1. .00 0. .00 XXXX3211

ATOM 3212 OE1 GLU B 57 -8. .642 63. .280 57. .096 1. .00 0. .00 XXXX3212

ATOM 3213 OE2 GLU B 57 -8. .599 62. .889 54. .937 1. .00 0. .00 XXXX3213

ATOM 3214 N PRO B 58 -5. .010 58. .578 56. .631 1. .00 0. .00 XXXX3214

ATOM 3215 CA PRO B 58 -3. .751 58. .443 55. .893 1. .00 0. .00 XXXX3215

ATOM 3216 C PRO B 58 -3. .722 59. .278 54. .617 1. .00 0. .00 XXXX3216

ATOM 3217 O PRO B 58 -4. .693 59. .299 53. .859 1. .00 0. .00 XXXX3217

ATOM 3218 CB PRO B 58 -3. .697 56. .949 55. .568 1. .00 0. .00 XXXX3218

ATOM 3219 CG PRO B 58 -5. .124 56. .521 55. .524 1. .00 0. .00 XXXX3219

ATOM 3220 CD PRO B 58 -5. .867 57. .386 56. .506 1. .00 0. .00 XXXX3220

ATOM 3221 N ILE B 59 -2. .606 59. .964 54. .393 1. .00 0. .00 XXXX3221

ATOM 3222 CA ILE B 59 -2. .379 60. .686 53. .150 1. .00 0. .00 XXXX3222

ATOM 3223 C ILE B 59 -1. .254 59. .984 52. .403 1. .00 0. .00 XXXX3223

ATOM 3224 O ILE B 59 -0. .088 60. .097 52. .778 1. .00 0. .00 XXXX3224

ATOM 3225 CB ILE B 59 -2. .005 62. .160 53. .397 1. .00 0. .00 XXXX3225

ATOM 3226 CGI ILE B 59 -3. .009 62. .820 54. .347 1. .00 0. .00 XXXX3226

ATOM 3227 CD1 ILE B 59 -4. .429 62. .842 53. .826 1. .00 0. .00 XXXX3227

ATOM 3228 CG2 ILE B 59 -1. .910 62. .918 52. .080 1. .00 0. .00 XXXX3228

ATOM 3229 N VAL B 60 -1. .609 59. .261 51. .346 1. .00 0. .00 XXXX3229

ATOM 3230 CA VAL B 60 -0. .652 58. .413 50. .646 1. .00 0. .00 XXXX3230

ATOM 3231 C VAL B 60 -0. .006 59. .124 49. .464 1. .00 0. .00 XXXX3231

ATOM 3232 O VAL B 60 -0. .694 59. .669 48. .601 1. .00 0. .00 XXXX3232

ATOM 3233 CB VAL B 60 -1. .320 57. .119 50. .147 1. .00 0. .00 XXXX3233

ATOM 3234 CGI VAL B 60 -0. .333 56. .288 49. .344 1. .00 0. .00 XXXX3234

ATOM 3235 CG2 VAL B 60 -1. .860 56. .321 51. .321 1. .00 0. .00 XXXX3235

ATOM 3236 N GLU B 61 1. .323 59. .113 49. .436 1. .00 0. .00 XXXX3236

ATOM 3237 CA GLU B 61 2. .081 59. .757 48. .370 1. .00 0. .00 XXXX3237

ATOM 3238 C GLU B 61 3. .098 58. .801 47. .751 1. .00 0. .00 XXXX3238

ATOM 3239 O GLU B 61 3. .772 58. .051 48. .458 1. .00 0. .00 XXXX3239

ATOM 3240 CB GLU B 61 2. .794 61. .006 48. .898 1. .00 0. .00 XXXX3240

ATOM 3241 CG GLU B 61 1. .860 62. .099 49. .395 1. .00 0. .00 XXXX3241

ATOM 3242 CD GLU B 61 1. .031 62. .713 48. .282 1. .00 0. .00 XXXX3242

ATOM 3243 OE1 GLU B 61 1. .485 62. .695 47. .119 1. .00 0. .00 XXXX3243

ATOM 3244 OE2 GLU B 61 -0. .076 63. .213 48. .572 1. .00 0. .00 XXXX3244

ATOM 3245 N ASP B 62 3. .200 58. .829 46. .427 1. .00 0. .00 XXXX3245

ATOM 3246 CA ASP B 62 4. .181 58. .020 45. .714 1. .00 0. .00 XXXX3246

ATOM 3247 C ASP B 62 5. .544 58. .710 45. .711 1. .00 0. .00 XXXX3247

ATOM 3248 O ASP B 62 5. .679 59. .826 45. .212 1. .00 0. .00 XXXX3248

ATOM 3249 CB ASP B 62 3. .710 57. .752 44. .280 1. .00 0. .00 XXXX3249

ATOM 3250 CG ASP B 62 4. .700 56. .923 43. .481 1. .00 0. .00 XXXX3250

ATOM 3251 OD1 ASP B 62 5. .525 56. .215 44. .096 1. .00 0. .00 XXXX3251

ATOM 3252 OD2 ASP B 62 4. .653 56. .981 42. .233 1. .00 0. .00 XXXX3252

ATOM 3253 N GLY B 63 6. .550 58. .045 46. .271 1. .00 0. .00 XXXX3253

ATOM 3254 CA GLY B 63 7. .907 58. .564 46. .242 1. .00 0. .00 XXXX3254

ATOM 3255 C GLY B 63 8. .593 58. .246 44. .926 1. .00 0. .00 XXXX3255

ATOM 3256 O GLY B 63 9. .611 58. .847 44. .582 1. .00 0. .00 XXXX3256

ATOM 3257 N ALA B 64 8. .024 57. .294 44. .192 1. .00 0. .00 XXXX3257

ATOM 3258 CA ALA B 64 8. .425 57. .006 42. .816 1. .00 0. .00 XXXX3258

ATOM 3259 C ALA B 64 9. .883 56. .569 42. .670 1. .00 0. .00 XXXX3259 Attorney Docket No. 35327-522001 WO

ATOM 3260 O ALA B 64 10. .492 56. .785 41. .621 1. .00 0. .00 XXXX3260

ATOM 3261 CB ALA B 64 8. .161 58. .223 41. .938 1. .00 0. .00 XXXX3261

ATOM 3262 N SER B 65 10. .434 55. .946 43. .709 1. .00 0. .00 XXXX3262

ATOM 3263 CA SER B 65 11. .823 55. .491 43. .687 1. .00 0. .00 XXXX3263

ATOM 3264 C SER B 65 12. .759 56. .636 43. .311 1. .00 0. .00 XXXX3264

ATOM 3265 O SER B 65 13. .835 56. .421 42. .750 1. .00 0. .00 XXXX3265

ATOM 3266 CB SER B 65 11. .996 54. .327 42. .706 1. .00 0. .00 XXXX3266

ATOM 3267 OG SER B 65 11. .090 53. .273 42. .989 1. .00 0. .00 XXXX3267

ATOM 3268 N ASP B 66 12. .340 57. .855 43. .631 1. .00 0. .00 XXXX3268

ATOM 3269 CA ASP B 66 13. .077 59. .048 43. .239 1. .00 0. .00 XXXX3269

ATOM 3270 C ASP B 66 13. .271 59. .939 44. .455 1. .00 0. .00 XXXX3270

ATOM 3271 O ASP B 66 12. .318 60. .503 44. .992 1. .00 0. .00 XXXX3271

ATOM 3272 CB ASP B 66 12. .348 59. .799 42. .124 1. .00 0. .00 XXXX3272

ATOM 3273 CG ASP B 66 13. .127 61. .001 41. .628 1. .00 0. .00 XXXX3273

ATOM 3274 OD1 ASP B 66 14. .143 60. .804 40. .927 1. .00 0. .00 XXXX3274

ATOM 3275 OD2 ASP B 66 12. .725 62. .141 41. .939 1. .00 0. .00 XXXX3275

ATOM 3276 N TRP B 67 14. .523 60. .050 44. .881 1. .00 0. .00 XXXX3276

ATOM 3277 CA TRP B 67 14. .870 60. .667 46. .154 1. .00 0. .00 XXXX3277

ATOM 3278 C TRP B 67 14. .465 62. .140 46. .230 1. .00 0. .00 XXXX3278

ATOM 3279 O TRP B 67 14. .002 62. .594 47. .275 1. .00 0. .00 XXXX3279

ATOM 3280 CB TRP B 67 16. .370 60. .494 46. .412 1. .00 0. .00 XXXX3280

ATOM 3281 CG TRP B 67 16. .889 59. .171 45. .903 1. .00 0. .00 XXXX3281

ATOM 3282 CD1 TRP B 67 18. .087 58. .944 45. .287 1. .00 0. .00 XXXX3282

ATOM 3283 CD2 TRP B 67 16. .215 57. .900 45. .945 1. .00 0. .00 XXXX3283

ATOM 3284 NE1 TRP B 67 18. .206 57. .616 44. .953 1. .00 0. .00 XXXX3284

ATOM 3285 CE2 TRP B 67 17. .070 56. .955 45. .344 1. .00 0. .00 XXXX3285

ATOM 3286 CE3 TRP B 67 14. .974 57. .471 46. .432 1. .00 0. .00 XXXX3286

ATOM 3287 CZ2 TRP B 67 16. .725 55. .608 45. .221 1. .00 0. .00 XXXX3287

ATOM 3288 CZ3 TRP B 67 14. .634 56. .129 46. .306 1. .00 0. .00 XXXX3288

ATOM 3289 CH2 TRP B 67 15. .505 55. .219 45. .708 1. .00 0. .00 XXXX3289

ATOM 3290 N PRO B 68 14. .645 62. .893 45. .132 1. .00 0. .00 XXXX3290

ATOM 3291 CA PRO B 68 14. .133 64. .268 45. .108 1. .00 0. .00 XXXX3291

ATOM 3292 C PRO B 68 12. .615 64. .321 45. .289 1. .00 0. .00 XXXX3292

ATOM 3293 O PRO B 68 12. .105 65. .221 45. .958 1. .00 0. .00 XXXX3293

ATOM 3294 CB PRO B 68 14. .536 64. .765 43. .719 1. .00 0. .00 XXXX3294

ATOM 3295 CG PRO B 68 15. .733 63. .952 43. .369 1. .00 0. .00 XXXX3295

ATOM 3296 CD PRO B 68 15. .457 62. .591 43. .940 1. .00 0. .00 XXXX3296

ATOM 3297 N THR B 69 11. .909 63. .363 44. .695 1. .00 0. .00 XXXX3297

ATOM 3298 CA THR B 69 10. .462 63. .263 44. .855 1. .00 0. .00 XXXX3298

ATOM 3299 C THR B 69 10. .078 62. .969 46. .300 1. .00 0. .00 XXXX3299

ATOM 3300 O THR B 69 9. .096 63. .507 46. .809 1. .00 0. .00 XXXX3300

ATOM 3301 CB THR B 69 9. .871 62. .171 43. .949 1. .00 0. .00 XXXX3301

ATOM 3302 OG1 THR B 69 10. .154 62. .485 42. .579 1. .00 0. .00 XXXX3302

ATOM 3303 CG2 THR B 69 8. .363 62. .075 44. .144 1. .00 0. .00 XXXX3303

ATOM 3304 N PHE B 70 10. .851 62. .104 46. .952 1. .00 0. .00 XXXX3304

ATOM 3305 CA PHE B 70 10. .633 61. .796 48. .362 1. .00 0. .00 XXXX3305

ATOM 3306 C PHE B 70 10. .716 63. .062 49. .208 1. .00 0. .00 XXXX3306

ATOM 3307 O PHE B 70 9. .897 63. .278 50. .101 1. .00 0. .00 XXXX3307

ATOM 3308 CB PHE B 70 11. .651 60. .764 48. .859 1. .00 0. .00 XXXX3308

ATOM 3309 CG PHE B 70 11. .194 59. .339 48. .717 1. .00 0. .00 XXXX3309

ATOM 3310 CD1 PHE B 70 10. .453 58. .732 49. .719 1. .00 0. .00 XXXX3310

ATOM 3311 CD2 PHE B 70 11. .513 58. .603 47. .588 1. .00 0. .00 XXXX3311

ATOM 3312 CE1 PHE B 70 10. .034 57. .421 49. .594 1. .00 0. .00 XXXX3312

ATOM 3313 CE2 PHE B 70 11. .096 57. .291 47. .458 1. .00 0. .00 XXXX3313

ATOM 3314 CZ PHE B 70 10. .356 56. .699 48. .462 1. .00 0. .00 XXXX3314

ATOM 3315 N ALA B 71 11. .714 63. .893 48. .919 1. .00 0. .00 XXXX3315

ATOM 3316 CA ALA B 71 11. .921 65. .141 49. .646 1. .00 0. .00 XXXX3316

ATOM 3317 C ALA B 71 10. .749 66. .100 49. .451 1. .00 0. .00 XXXX3317

ATOM 3318 O ALA B 71 10. .236 66. .669 50. .416 1. .00 0. .00 XXXX3318

ATOM 3319 CB ALA B 71 13. .224 65. .802 49. .210 1. .00 0. .00 XXXX3319

ATOM 3320 N GLU B 72 10. .335 66. .281 48. .200 1. .00 0. .00 XXXX3320

ATOM 3321 CA GLU B 72 9. .223 67. .172 47. .881 1. .00 0. .00 XXXX3321

ATOM 3322 C GLU B 72 7. .914 66. .696 48. .502 1. .00 0. .00 XXXX3322

ATOM 3323 O GLU B 72 7. .141 67. .497 49. .025 1. .00 0. .00 XXXX3323

ATOM 3324 CB GLU B 72 9. .064 67. .313 46. .366 1. .00 0. .00 XXXX3324

ATOM 3325 CG GLU B 72 10. .132 68. .172 45. .709 1. .00 0. .00 XXXX3325

ATOM 3326 CD GLU B 72 10. .236 69. .549 46. .342 1. .00 0. .00 XXXX3326 Attorney Docket No. 35327-522001 WO

ATOM 3327 OE1 GLU B 72 9. .200 70. .240 46. .441 1. .00 0. .00 XXXX3327

ATOM 3328 OE2 GLU B 72 11. .356 69. .944 46. .737 1. .00 0. .00 XXXX3328

ATOM 3329 N LYS B 73 7. .671 65. .392 48. .443 1. .00 0. .00 XXXX3329

ATOM 3330 CA LYS B 73 6. .466 64. .815 49. .028 1. .00 0. .00 XXXX3330

ATOM 3331 C LYS B 73 6. .451 64. .986 50. .543 1. .00 0. .00 XXXX3331

ATOM 3332 O LYS B 73 5. .409 65. .269 51. .133 1. .00 0. .00 XXXX3332

ATOM 3333 CB LYS B 73 6. .351 63. .334 48. .666 1. .00 0. .00 XXXX3333

ATOM 3334 CG LYS B 73 6. .074 63. .069 47. .197 1. .00 0. .00 XXXX3334

ATOM 3335 CD LYS B 73 4. .739 63. .663 46. .781 1. .00 0. .00 XXXX3335

ATOM 3336 CE LYS B 73 4. .412 63. .336 45. .333 1. .00 0. .00 XXXX3336

ATOM 3337 NZ LYS B 73 3. .068 63. .847 44. .941 1. .00 0. .00 XXXX3337

ATOM 3338 N ALA B 74 7. .610 64. .810 51. .167 1. .00 0. .00 XXXX3338

ATOM 3339 CA ALA B 74 7. .730 64. .985 52. .609 1. .00 0. .00 XXXX3339

ATOM 3340 C ALA B 74 7. .413 66. .425 52. .998 1. .00 0. .00 XXXX3340

ATOM 3341 O ALA B 74 6. .761 66. .676 54. .011 1. .00 0. .00 XXXX3341

ATOM 3342 CB ALA B 74 9. .121 64. .597 53. .081 1. .00 0. .00 XXXX3342

ATOM 3343 N LYS B 75 7. .880 67. .366 52. .182 1. .00 0. .00 XXXX3343

ATOM 3344 CA LYS B 75 7. .631 68. .784 52. .415 1. .00 0. .00 XXXX3344

ATOM 3345 C LYS B 75 6. .141 69. .105 52. .307 1. .00 0. .00 XXXX3345

ATOM 3346 O LYS B 75 5. .587 69. .805 53. .155 1. .00 0. .00 XXXX3346

ATOM 3347 CB LYS B 75 8. .431 69. .639 51. .430 1. .00 0. .00 XXXX3347

ATOM 3348 CG LYS B 75 8. .344 71. .133 51. .703 1. .00 0. .00 XXXX3348

ATOM 3349 CD LYS B 75 9. .277 71. .924 50. .801 1. .00 0. .00 XXXX3349

ATOM 3350 CE LYS B 75 9. .225 73. .409 51. .124 1. .00 0. .00 XXXX3350

ATOM 3351 NZ LYS B 75 10. .160 74. .198 50. .274 1. .00 0. .00 XXXX3351

ATOM 3352 N LYS B 76 5. .502 68. .593 51. .260 1. .00 0. .00 XXXX3352

ATOM 3353 CA LYS B 76 4. .065 68. .774 51. .069 1. .00 0. .00 XXXX3353

ATOM 3354 C LYS B 76 3. .255 68. .183 52. .221 1. .00 0. .00 XXXX3354

ATOM 3355 O LYS B 76 2. .336 68. .823 52. .734 1. .00 0. .00 XXXX3355

ATOM 3356 CB LYS B 76 3. .617 68. .144 49. .749 1. .00 0. .00 XXXX3356

ATOM 3357 CG LYS B 76 2. .107 68. .044 49. .600 1. .00 0. .00 XXXX3357

ATOM 3358 CD LYS B 76 1. .717 67. .390 48. .286 1. .00 0. .00 XXXX3358

ATOM 3359 CE LYS B 76 1. .038 66. .050 48. .516 1. .00 0. .00 XXXX3359

ATOM 3360 NZ LYS B 76 -0. .234 66. .188 49. .280 1. .00 0. .00 XXXX3360

ATOM 3361 N LEU B 77 3. .601 66. .964 52. .622 1. .00 0. .00 XXXX3361

ATOM 3362 CA LEU B 77 2. .886 66. .272 53. .692 1. .00 0. .00 XXXX3362

ATOM 3363 C LEU B 77 2. .960 67. .031 55. .013 1. .00 0. .00 XXXX3363

ATOM 3364 O LEU B 77 1. .988 67. .080 55. .766 1. .00 0. .00 XXXX3364

ATOM 3365 CB LEU B 77 3. .437 64. .856 53. .874 1. .00 0. .00 XXXX3365

ATOM 3366 CG LEU B 77 2. .976 63. .820 52. .847 1. .00 0. .00 XXXX3366

ATOM 3367 CD1 LEU B 77 3. .788 62. .538 52. .970 1. .00 0. .00 XXXX3367

ATOM 3368 CD2 LEU B 77 1. .486 63. .538 53. .004 1. .00 0. .00 XXXX3368

ATOM 3369 N LEU B 78 4. .117 67. .623 55. .291 1. .00 0. .00 XXXX3369

ATOM 3370 CA LEU B 78 4. .315 68. .343 56. .543 1. .00 0. .00 XXXX3370

ATOM 3371 C LEU B 78 3. .735 69. .754 56. .501 1. .00 0. .00 XXXX3371

ATOM 3372 O LEU B 78 3. .113 70. .206 57. .463 1. .00 0. .00 XXXX3372

ATOM 3373 CB LEU B 78 5. .805 68. .412 56. .886 1. .00 0. .00 XXXX3373

ATOM 3374 CG LEU B 78 6. .503 67. .091 57. .218 1. .00 0. .00 XXXX3374

ATOM 3375 CD1 LEU B 78 7. .990 67. .315 57. .447 1. .00 0. .00 XXXX3375

ATOM 3376 CD2 LEU B 78 5. .863 66. .433 58. .431 1. .00 0. .00 XXXX3376

ATOM 3377 N GLN B 79 3. .941 70. .449 55. .388 1. .00 0. .00 XXXX3377

ATOM 3378 CA GLN B 79 3. .589 71. .863 55. .299 1. .00 0. .00 XXXX3378

ATOM 3379 C GLN B 79 2. .191 72. .129 54. .738 1. .00 0. .00 XXXX3379

ATOM 3380 O GLN B 79 1. .518 73. .063 55. .171 1. .00 0. .00 XXXX3380

ATOM 3381 CB GLN B 79 4. .636 72. .605 54. .464 1. .00 0. .00 XXXX3381

ATOM 3382 CG GLN B 79 6. .012 72. .632 55. .113 1. .00 0. .00 XXXX3382

ATOM 3383 CD GLN B 79 7. .008 73. .483 54. .353 1. .00 0. .00 XXXX3383

ATOM 3384 OE1 GLN B 79 6. .693 74. .041 53. .303 1. .00 0. .00 XXXX3384

ATOM 3385 NE2 GLN B 79 8. .220 73. .592 54. .886 1. .00 0. .00 XXXX3385

ATOM 3386 N LYS B 80 1. .754 71. .319 53. .778 1. .00 0. .00 XXXX3386

ATOM 3387 CA LYS B 80 0. .447 71. .532 53. .162 1. .00 0. .00 XXXX3387

ATOM 3388 C LYS B 80 -0. .640 70. .662 53. .785 1. .00 0. .00 XXXX3388

ATOM 3389 O LYS B 80 -1. .696 71. .162 54. .174 1. .00 0. .00 XXXX3389

ATOM 3390 CB LYS B 80 0. .515 71. .274 51. .655 1. .00 0. .00 XXXX3390

ATOM 3391 CG LYS B 80 1. .393 72. .255 50. .897 1. .00 0. .00 XXXX3391

ATOM 3392 CD LYS B 80 0. .822 73. .663 50. .963 1. .00 0. .00 XXXX3392

ATOM 3393 CE LYS B 80 1. .635 74. .636 50. .124 1. .00 0. .00 XXXX3393 Attorney Docket No. 35327-522001 WO

ATOM 3394 NZ LYS B 80 1. .642 74. .260 48. .682 1. .00 0. .00 XXXX3394

ATOM 3395 N ASP B 81 -0. .382 69. .362 53. .880 1. .00 0. .00 XXXX3395

ATOM 3396 CA ASP B 81 -1. .349 68. .441 54. .463 1. .00 0. .00 XXXX3396

ATOM 3397 C ASP B 81 -1. .303 68. .521 55. .983 1. .00 0. .00 XXXX3397

ATOM 3398 O ASP B 81 -2. .265 68. .167 56. .666 1. .00 0. .00 XXXX3398

ATOM 3399 CB ASP B 81 -1. .084 67. .009 53. .994 1. .00 0. .00 XXXX3399

ATOM 3400 CG ASP B 81 -1. .237 66. .851 52. .494 1. .00 0. .00 XXXX3400

ATOM 3401 OD1 ASP B 81 -2. .301 67. .228 51. .960 1. .00 0. .00 XXXX3401

ATOM 3402 OD2 ASP B 81 -0. .293 66. .348 51. .849 1. .00 0. .00 XXXX3402

ATOM 3403 N LYS B 82 -0. .175 69. .002 56. .498 1. .00 0. .00 XXXX3403

ATOM 3404 CA LYS B 82 0. .039 69. .157 57. .933 1. .00 0. .00 XXXX3404

ATOM 3405 C LYS B 82 -0. .203 67. .865 58. .708 1. .00 0. .00 XXXX3405

ATOM 3406 O LYS B 82 -0. .942 67. .849 59. .691 1. .00 0. .00 XXXX3406

ATOM 3407 CB LYS B 82 -0. .855 70. .272 58. .478 1. .00 0. .00 XXXX3407

ATOM 3408 CG LYS B 82 -0. .507 71. .648 57. .932 1. .00 0. .00 XXXX3408

ATOM 3409 CD LYS B 82 -1. .493 72. .702 58. .405 1. .00 0. .00 XXXX3409

ATOM 3410 CE LYS B 82 -1. .203 74. .048 57. .762 1. .00 0. .00 XXXX3410

ATOM 3411 NZ LYS B 82 0. .231 74. .429 57. .894 1. .00 0. .00 XXXX3411

ATOM 3412 N VAL B 83 0. .422 66. .783 58. .255 1. .00 0. .00 XXXX3412

ATOM 3413 CA VAL B 83 0. .317 65. .499 58. .936 1. .00 0. .00 XXXX3413

ATOM 3414 C VAL B 83 1. .063 65. .539 60. .265 1. .00 0. .00 XXXX3414

ATOM 3415 O VAL B 83 1. .942 66. .377 60. .466 1. .00 0. .00 XXXX3415

ATOM 3416 CB VAL B 83 0. .875 64. .350 58. .074 1. .00 0. .00 XXXX3416

ATOM 3417 CGI VAL B 83 0. .137 64. .279 56. .741 1. .00 0. .00 XXXX3417

ATOM 3418 CG2 VAL B 83 2. .372 64. .525 57. .856 1. .00 0. .00 XXXX3418

ATOM 3419 N ALA B 84 0. .711 64. .632 61. .171 1. .00 0. .00 XXXX3419

ATOM 3420 CA ALA B 84 1. .361 64. .567 62. .476 1. .00 0. .00 XXXX3420

ATOM 3421 C ALA B 84 2. .642 63. .748 62. .403 1. .00 0. .00 XXXX3421

ATOM 3422 O ALA B 84 3. .512 63. .858 63. .267 1. .00 0. .00 XXXX3422

ATOM 3423 CB ALA B 84 0. .417 63. .979 63. .512 1. .00 0. .00 XXXX3423

ATOM 3424 N VAL B 85 2. .748 62. .924 61. .367 1. .00 0. .00 XXXX3424

ATOM 3425 CA VAL B 85 3. .866 62. .002 61. .225 1. .00 0. .00 XXXX3425

ATOM 3426 C VAL B 85 3. .896 61. .422 59. .817 1. .00 0. .00 XXXX3426

ATOM 3427 O VAL B 85 2. .869 61. .357 59. .143 1. .00 0. .00 XXXX3427

ATOM 3428 CB VAL B 85 3. .785 60. .849 62. .249 1. .00 0. .00 XXXX3428

ATOM 3429 CGI VAL B 85 2. .531 60. .021 62. .018 1. .00 0. .00 XXXX3429

ATOM 3430 CG2 VAL B 85 5. .024 59. .971 62. .168 1. .00 0. .00 XXXX3430

ATOM 3431 N ILE B 86 5. .077 61. .009 59. .374 1. .00 0. .00 XXXX3431

ATOM 3432 CA ILE B 86 5. .208 60. .329 58. .096 1. .00 0. .00 XXXX3432

ATOM 3433 C ILE B 86 5. .740 58. .914 58. .282 1. .00 0. .00 XXXX3433

ATOM 3434 O ILE B 86 6. .769 58. .705 58. .923 1. .00 0. .00 XXXX3434

ATOM 3435 CB ILE B 86 6. .144 61. .090 57. .137 1. .00 0. .00 XXXX3435

ATOM 3436 CGI ILE B 86 5. .607 62. .497 56. .864 1. .00 0. .00 XXXX3436

ATOM 3437 CD1 ILE B 86 6. .550 63. .359 56. .051 1. .00 0. .00 XXXX3437

ATOM 3438 CG2 ILE B 86 6. .320 60. .318 55. .835 1. .00 0. .00 XXXX3438

ATOM 3439 N PHE B 87 5. .023 57. .944 57. .726 1. .00 0. .00 XXXX3439

ATOM 3440 CA PHE B 87 5. .529 56. .582 57. .631 1. .00 0. .00 XXXX3440

ATOM 3441 C PHE B 87 6. .019 56. .349 56. .208 1. .00 0. .00 XXXX3441

ATOM 3442 O PHE B 87 5. .255 56. .511 55. .257 1. .00 0. .00 XXXX3442

ATOM 3443 CB PHE B 87 4. .446 55. .565 58. .000 1. .00 0. .00 XXXX3443

ATOM 3444 CG PHE B 87 3. .816 55. .806 59. .345 1. .00 0. .00 XXXX3444

ATOM 3445 CD1 PHE B 87 4. .454 55. .403 60. .506 1. .00 0. .00 XXXX3445

ATOM 3446 CD2 PHE B 87 2. .582 56. .427 59. .446 1. .00 0. .00 XXXX3446

ATOM 3447 CE1 PHE B 87 3. .876 55. .621 61. .745 1. .00 0. .00 XXXX3447

ATOM 3448 CE2 PHE B 87 1. .998 56. .649 60. .680 1. .00 0. .00 XXXX3448

ATOM 3449 CZ PHE B 87 2. .647 56. .245 61. .831 1. .00 0. .00 XXXX3449

ATOM 3450 N GLY B 88 7. .284 55. .974 56. .047 1. .00 0. .00 XXXX3450

ATOM 3451 CA GLY B 88 7. .797 55. .751 54. .709 1. .00 0. .00 XXXX3451

ATOM 3452 C GLY B 88 9. .300 55. .660 54. .543 1. .00 0. .00 XXXX3452

ATOM 3453 O GLY B 88 10. .046 55. .559 55. .519 1. .00 0. .00 XXXX3453

ATOM 3454 N ALA B 89 9. .719 55. .692 53. .279 1. .00 0. .00 XXXX3454

ATOM 3455 CA ALA B 89 11. .110 55. .541 52. .853 1. .00 0. .00 XXXX3455

ATOM 3456 C ALA B 89 11. .555 54. .082 52. .927 1. .00 0. .00 XXXX3456

ATOM 3457 O ALA B 89 10. .989 53. .282 53. .671 1. .00 0. .00 XXXX3457

ATOM 3458 CB ALA B 89 12. .037 56. .428 53. .684 1. .00 0. .00 XXXX3458

ATOM 3459 N TRP B 90 12. .572 53. .749 52. .138 1. .00 0. .00 XXXX3459

ATOM 3460 CA TRP B 90 13. .183 52. .425 52. .160 1. .00 0. .00 XXXX3460 Attorney Docket No. 35327-522001 WO

ATOM 3461 C TRP B 90 14. .684 52. .580 51. .972 1. .00 0. .00 XXXX3461

ATOM 3462 O TRP B 90 15. .461 52. .312 52. .886 1. .00 0. .00 XXXX3462

ATOM 3463 CB TRP B 90 12. .588 51. .518 51. .076 1. .00 0. .00 XXXX3463

ATOM 3464 CG TRP B 90 13. .260 50. .167 50. .957 1. .00 0. .00 XXXX3464

ATOM 3465 CD1 TRP B 90 14. .537 49. .916 50. .534 1. .00 0. .00 XXXX3465

ATOM 3466 CD2 TRP B 90 12. .682 48. .888 51. .253 1. .00 0. .00 XXXX3466

ATOM 3467 NE1 TRP B 90 14. .789 48. .567 50. .555 1. .00 0. .00 XXXX3467

ATOM 3468 CE2 TRP B 90 13. .668 47. .913 50. .990 1. .00 0. .00 XXXX3468

ATOM 3469 CE3 TRP B 90 11. .429 48. .472 51. .714 1. .00 0. .00 XXXX3469

ATOM 3470 CZ2 TRP B 90 13. .440 46. .551 51. .177 1. .00 0. .00 XXXX3470

ATOM 3471 CZ3 TRP B 90 11. .204 47. .119 51. .898 1. .00 0. .00 XXXX3471

ATOM 3472 CH2 TRP B 90 12. .205 46. .175 51. .629 1. .00 0. .00 XXXX3472

ATOM 3473 N THR B 91 15. .087 53. .005 50. .778 1. .00 0. .00 XXXX3473

ATOM 3474 CA THR B 91 16. .499 53. .226 50. .498 1. .00 0. .00 XXXX3474

ATOM 3475 C THR B 91 17. .026 54. .335 51. .399 1. .00 0. .00 XXXX3475

ATOM 3476 O THR B 91 16. .305 55. .280 51. .716 1. .00 0. .00 XXXX3476

ATOM 3477 CB THR B 91 16. .747 53. .606 49. .023 1. .00 0. .00 XXXX3477

ATOM 3478 OG1 THR B 91 16. .165 54. .886 48. .750 1. .00 0. .00 XXXX3478

ATOM 3479 CG2 THR B 91 16. .149 52. .563 48. .087 1. .00 0. .00 XXXX3479

ATOM 3480 N SER B 92 18. .281 54. .217 51. .816 1. .00 0. .00 XXXX3480

ATOM 3481 CA SER B 92 18. .903 55. .246 52. .637 1. .00 0. .00 XXXX3481

ATOM 3482 C SER B 92 19. .003 56. .551 51. .857 1. .00 0. .00 XXXX3482

ATOM 3483 O SER B 92 19. .082 57. .632 52. .442 1. .00 0. .00 XXXX3483

ATOM 3484 CB SER B 92 20. .282 54. .794 53. .116 1. .00 0. .00 XXXX3484

ATOM 3485 OG SER B 92 20. .167 53. .702 54. .012 1. .00 0. .00 XXXX3485

ATOM 3486 N ALA B 93 18. .993 56. .442 50. .533 1. .00 0. .00 XXXX3486

ATOM 3487 CA ALA B 93 18. .954 57. .614 49. .669 1. .00 0. .00 XXXX3487

ATOM 3488 C ALA B 93 17. .653 58. .377 49. .888 1. .00 0. .00 XXXX3488

ATOM 3489 O ALA B 93 17. .651 59. .600 50. .026 1. .00 0. .00 XXXX3489

ATOM 3490 CB ALA B 93 19. .099 57. .208 48. .211 1. .00 0. .00 XXXX3490

ATOM 3491 N SER B 94 16. .547 57. .643 49. .925 1. .00 0. .00 XXXX3491

ATOM 3492 CA SER B 94 15. .245 58. .249 50. .158 1. .00 0. .00 XXXX3492

ATOM 3493 C SER B 94 15. .138 58. .768 51. .589 1. .00 0. .00 XXXX3493

ATOM 3494 O SER B 94 14. .581 59. .840 51. .825 1. .00 0. .00 XXXX3494

ATOM 3495 CB SER B 94 14. .124 57. .247 49. .871 1. .00 0. .00 XXXX3495

ATOM 3496 OG SER B 94 14. .126 56. .191 50. .816 1. .00 0. .00 XXXX3496

ATOM 3497 N ARG B 95 15. .673 58. .010 52. .543 1. .00 0. .00 XXXX3497

ATOM 3498 CA ARG B 95 15. .622 58. .420 53. .943 1. .00 0. .00 XXXX3498

ATOM 3499 C ARG B 95 16. .429 59. .694 54. .165 1. .00 0. .00 XXXX3499

ATOM 3500 O ARG B 95 15. .975 60. .615 54. .842 1. .00 0. .00 XXXX3500

ATOM 3501 CB ARG B 95 16. .136 57. .314 54. .870 1. .00 0. .00 XXXX3501

ATOM 3502 CG ARG B 95 15. .871 57. .604 56. .346 1. .00 0. .00 XXXX3502

ATOM 3503 CD ARG B 95 16. .634 56. .679 57. .287 1. .00 0. .00 XXXX3503

ATOM 3504 NE ARG B 95 18. .081 56. .863 57. .196 1. .00 0. .00 XXXX3504

ATOM 3505 CZ ARG B 95 18. .902 56. .047 56. .542 1. .00 0. .00 XXXX3505

ATOM 3506 NH1 ARG B 95 18. .423 54. .974 55. .928 1. .00 0. .00 XXXX3506

ATOM 3507 NH2 ARG B 95 20. .203 56. .298 56. .512 1. .00 0. .00 XXXX3507

ATOM 3508 N LYS B 96 17. .627 59. .740 53. .588 1. .00 0. .00 XXXX3508

ATOM 3509 CA LYS B 96 18. .511 60. .887 53. .761 1. .00 0. .00 XXXX3509

ATOM 3510 C LYS B 96 18. .011 62. .113 53. .003 1. .00 0. .00 XXXX3510

ATOM 3511 O LYS B 96 18. .399 63. .239 53. .314 1. .00 0. .00 XXXX3511

ATOM 3512 CB LYS B 96 19. .938 60. .539 53. .330 1. .00 0. .00 XXXX3512

ATOM 3513 CG LYS B 96 20. .702 59. .740 54. .374 1. .00 0. .00 XXXX3513

ATOM 3514 CD LYS B 96 22. .131 59. .468 53. .946 1. .00 0. .00 XXXX3514

ATOM 3515 CE LYS B 96 22. .839 58. .579 54. .956 1. .00 0. .00 XXXX3515

ATOM 3516 NZ LYS B 96 22. .991 59. .251 56. .278 1. .00 0. .00 XXXX3516

ATOM 3517 N ALA B 97 17. .159 61. .895 52. .006 1. .00 0. .00 XXXX3517

ATOM 3518 CA ALA B 97 16. .509 63. .002 51. .312 1. .00 0. .00 XXXX3518

ATOM 3519 C ALA B 97 15. .403 63. .608 52. .175 1. .00 0. .00 XXXX3519

ATOM 3520 O ALA B 97 15. .170 64. .816 52. .147 1. .00 0. .00 XXXX3520

ATOM 3521 CB ALA B 97 15. .945 62. .538 49. .976 1. .00 0. .00 XXXX3521

ATOM 3522 N VAL B 98 14. .732 62. .758 52. .946 1. .00 0. .00 XXXX3522

ATOM 3523 CA VAL B 98 13. .649 63. .190 53. .825 1. .00 0. .00 XXXX3523

ATOM 3524 C VAL B 98 14. .186 63. .793 55. .123 1. .00 0. .00 XXXX3524

ATOM 3525 O VAL B 98 13. .556 64. .667 55. .721 1. .00 0. .00 XXXX3525

ATOM 3526 CB VAL B 98 12. .704 62. .018 54. .164 1. .00 0. .00 XXXX3526

ATOM 3527 CGI VAL B 98 11. .710 62. .420 55. .245 1. .00 0. .00 XXXX3527 Attorney Docket No. 35327-522001 WO

ATOM 3528 CG2 VAL B 98 11. .978 61. .544 52. .913 1. .00 0. .00 XXXX3528

ATOM 3529 N LEU B 99 15. .355 63. .319 55. .543 1. .00 0. .00 XXXX3529

ATOM 3530 CA LEU B 99 15. .948 63. .693 56. .826 1. .00 0. .00 XXXX3530

ATOM 3531 C LEU B 99 16. .012 65. .204 57. .054 1. .00 0. .00 XXXX3531

ATOM 3532 O LEU B 99 15. .560 65. .693 58. .089 1. .00 0. .00 XXXX3532

ATOM 3533 CB LEU B 99 17. .352 63. .087 56. .943 1. .00 0. .00 XXXX3533

ATOM 3534 CG LEU B 99 18. .123 63. .280 58. .252 1. .00 0. .00 XXXX3534

ATOM 3535 CD1 LEU B 99 19. .194 62. .210 58. .392 1. .00 0. .00 XXXX3535

ATOM 3536 CD2 LEU B 99 18. .753 64. .664 58. .317 1. .00 0. .00 XXXX3536

ATOM 3537 N PRO B 100 16. .576 65. .951 56. .091 1. .00 0. .00 XXXX3537

ATOM 3538 CA PRO B 100 16. .666 67. .405 56. .256 1. .00 0. .00 XXXX3538

ATOM 3539 C PRO B 100 15. .292 68. .071 56. .305 1. .00 0. .00 XXXX3539

ATOM 3540 O PRO B 100 15. .140 69. .120 56. .931 1. .00 0. .00 XXXX3540

ATOM 3541 CB PRO B 100 17. .451 67. .855 55. .016 1. .00 0. .00 XXXX3541

ATOM 3542 CG PRO B 100 17. .263 66. .757 54. .024 1. .00 0. .00 XXXX3542

ATOM 3543 CD PRO B 100 17. .185 65. .499 54. .829 1. .00 0. .00 XXXX3543

ATOM 3544 N VAL B 101 14. .304 67. .464 55. .656 1. .00 0. .00 XXXX3544

ATOM 3545 CA VAL B 101 12. .957 68. .022 55. .634 1. .00 0. .00 XXXX3545

ATOM 3546 C VAL B 101 12. .251 67. .885 56. .984 1. .00 0. .00 XXXX3546

ATOM 3547 O VAL B 101 11. .661 68. .845 57. .481 1. .00 0. .00 XXXX3547

ATOM 3548 CB VAL B 101 12. .093 67. .358 54. .545 1. .00 0. .00 XXXX3548

ATOM 3549 CGI VAL B 101 10. .699 67. .962 54. .536 1. .00 0. .00 XXXX3549

ATOM 3550 CG2 VAL B 101 12. .753 67. .508 53. .181 1. .00 0. .00 XXXX3550

ATOM 3551 N VAL B 102 12. .308 66. .694 57. .574 1. .00 0. .00 XXXX3551

ATOM 3552 CA VAL B 102 11. .676 66. .465 58. .870 1. .00 0. .00 XXXX3552

ATOM 3553 C VAL B 102 12. .424 67. .180 59. .990 1. .00 0. .00 XXXX3553

ATOM 3554 O VAL B 102 11. .818 67. .623 60. .963 1. .00 0. .00 XXXX3554

ATOM 3555 CB VAL B 102 11. .581 64. .962 59. .208 1. .00 0. .00 XXXX3555

ATOM 3556 CGI VAL B 102 10. .475 64. .306 58. .396 1. .00 0. .00 XXXX3556

ATOM 3557 CG2 VAL B 102 12. .921 64. .272 58. .980 1. .00 0. .00 XXXX3557

ATOM 3558 N GLU B 103 13. .740 67. .298 59. .847 1. .00 0. .00 XXXX3558

ATOM 3559 CA GLU B 103 14. .544 68. .004 60. .839 1. .00 0. .00 XXXX3559

ATOM 3560 C GLU B 103 14. .252 69. .501 60. .794 1. .00 0. .00 XXXX3560

ATOM 3561 O GLU B 103 14. .123 70. .150 61. .833 1. .00 0. .00 XXXX3561

ATOM 3562 CB GLU B 103 16. .039 67. .744 60. .627 1. .00 0. .00 XXXX3562

ATOM 3563 CG GLU B 103 16. .488 66. .345 61. .027 1. .00 0. .00 XXXX3563

ATOM 3564 CD GLU B 103 17. .995 66. .234 61. .189 1. .00 0. .00 XXXX3564

ATOM 3565 OE1 GLU B 103 18. .704 67. .224 60. .910 1. .00 0. .00 XXXX3565

ATOM 3566 OE2 GLU B 103 18. .470 65. .157 61. .607 1. .00 0. .00 XXXX3566

ATOM 3567 N GLU B 104 14. .154 70. .044 59. .585 1. .00 0. .00 XXXX3567

ATOM 3568 CA GLU B 104 13. .915 71. .470 59. .398 1. .00 0. .00 XXXX3568

ATOM 3569 C GLU B 104 12. .524 71. .885 59. .871 1. .00 0. .00 XXXX3569

ATOM 3570 O GLU B 104 12. .341 72. .978 60. .408 1. .00 0. .00 XXXX3570

ATOM 3571 CB GLU B 104 14. .089 71. .842 57. .924 1. .00 0. .00 XXXX3571

ATOM 3572 CG GLU B 104 14. .168 73. .334 57. .655 1. .00 0. .00 XXXX3572

ATOM 3573 CD GLU B 104 14. .268 73. .654 56. .175 1. .00 0. .00 XXXX3573

ATOM 3574 OE1 GLU B 104 13. .918 72. .782 55. .350 1. .00 0. .00 XXXX3574

ATOM 3575 OE2 GLU B 104 14. .696 74. .778 55. .837 1. .00 0. .00 XXXX3575

ATOM 3576 N ASN B 105 11. .548 71. .007 59. .670 1. .00 0. .00 XXXX3576

ATOM 3577 CA ASN B 105 10. .170 71. .286 60. .061 1. .00 0. .00 XXXX3577

ATOM 3578 C ASN B 105 9. .822 70. .721 61. .435 1. .00 0. .00 XXXX3578

ATOM 3579 O ASN B 105 8. .689 70. .856 61. .899 1. .00 0. .00 XXXX3579

ATOM 3580 CB ASN B 105 9. .206 70. .728 59. .013 1. .00 0. .00 XXXX3580

ATOM 3581 CG ASN B 105 9. .323 71. .437 57. .679 1. .00 0. .00 XXXX3581

ATOM 3582 OD1 ASN B 105 8. .691 72. .469 57. .452 1. .00 0. .00 XXXX3582

ATOM 3583 ND2 ASN B 105 10. .138 70. .887 56. .788 1. .00 0. .00 XXXX3583

ATOM 3584 N ASN B 106 10. .806 70. .102 62. .080 1. .00 0. .00 XXXX3584

ATOM 3585 CA ASN B 106 10. .585 69. .353 63. .314 1. .00 0. .00 XXXX3585

ATOM 3586 C ASN B 106 9. .414 68. .385 63. .179 1. .00 0. .00 XXXX3586

ATOM 3587 O ASN B 106 8. .528 68. .336 64. .032 1. .00 0. .00 XXXX3587

ATOM 3588 CB ASN B 106 10. .347 70. .298 64. .494 1. .00 0. .00 XXXX3588

ATOM 3589 CG ASN B 106 10. .507 69. .602 65. .837 1. .00 0. .00 XXXX3589

ATOM 3590 OD1 ASN B 106 11. .260 68. .636 65. .961 1. .00 0. .00 XXXX3590

ATOM 3591 ND2 ASN B 106 9. .793 70. .088 66. .847 1. .00 0. .00 XXXX3591

ATOM 3592 N GLY B 107 9. .416 67. .619 62. .094 1. .00 0. .00 XXXX3592

ATOM 3593 CA GLY B 107 8. .422 66. .585 61. .893 1. .00 0. .00 XXXX3593

ATOM 3594 C GLY B 107 8. .969 65. .247 62. .342 1. .00 0. .00 XXXX3594 Attorney Docket No. 35327-522001 WO

ATOM 3595 O GLY B 107 10. .068 65. .172 62. .894 1. .00 0. .00 XXXX3595

ATOM 3596 N LEU B 108 8. .208 64. .185 62. .106 1. .00 0. .00 XXXX3596

ATOM 3597 CA LEU B 108 8. .669 62. .845 62. .442 1. .00 0. .00 XXXX3597

ATOM 3598 C LEU B 108 8. .532 61. .891 61. .266 1. .00 0. .00 XXXX3598

ATOM 3599 O LEU B 108 7. .497 61. .849 60. .602 1. .00 0. .00 XXXX3599

ATOM 3600 CB LEU B 108 7. .898 62. .293 63. .644 1. .00 0. .00 XXXX3600

ATOM 3601 CG LEU B 108 8. .224 62. .892 65. .013 1. .00 0. .00 XXXX3601

ATOM 3602 CD1 LEU B 108 7. .429 62. .188 66. .101 1. .00 0. .00 XXXX3602

ATOM 3603 CD2 LEU B 108 9. .718 62. .813 65. .297 1. .00 0. .00 XXXX3603

ATOM 3604 N LEU B 109 9. .593 61. .133 61. .014 1. .00 0. .00 XXXX3604

ATOM 3605 CA LEU B 109 9. .555 60. .031 60. .064 1. .00 0. .00 XXXX3605

ATOM 3606 C LEU B 109 9. .713 58. .703 60. .790 1. .00 0. .00 XXXX3606

ATOM 3607 O LEU B 109 10. .671 58. .511 61. .539 1. .00 0. .00 XXXX3607

ATOM 3608 CB LEU B 109 10. .655 60. .180 59. .010 1. .00 0. .00 XXXX3608

ATOM 3609 CG LEU B 109 10. .838 58. .982 58. .072 1. .00 0. .00 XXXX3609

ATOM 3610 CD1 LEU B 109 9. .686 58. .879 57. .082 1. .00 0. .00 XXXX3610

ATOM 3611 CD2 LEU B 109 12. .178 59. .056 57. .349 1. .00 0. .00 XXXX3611

ATOM 3612 N PHE B 110 8. .772 57. .791 60. .575 1. .00 0. .00 XXXX3612

ATOM 3613 CA PHE B 110 8. .943 56. .423 61. .043 1. .00 0. .00 XXXX3613

ATOM 3614 C PHE B 110 9. .407 55. .542 59. .886 1. .00 0. .00 XXXX3614

ATOM 3615 O PHE B 110 8. .665 55. .278 58. .938 1. .00 0. .00 XXXX3615

ATOM 3616 CB PHE B 110 7. .655 55. .892 61. .679 1. .00 0. .00 XXXX3616

ATOM 3617 CG PHE B 110 7. .549 56. .189 63. .151 1. .00 0. .00 XXXX3617

ATOM 3618 CD1 PHE B 110 7. .386 57. .489 63. .600 1. .00 0. .00 XXXX3618

ATOM 3619 CD2 PHE B 110 7. .643 55. .171 64. .087 1. .00 0. .00 XXXX3619

ATOM 3620 CE1 PHE B 110 7. .303 57. .768 64. .954 1. .00 0. .00 XXXX3620

ATOM 3621 CE2 PHE B 110 7. .561 55. .443 65. .443 1. .00 0. .00 XXXX3621

ATOM 3622 CZ PHE B 110 7. .391 56. .743 65. .876 1. .00 0. .00 XXXX3622

ATOM 3623 N TYR B 111 10. .657 55. .105 59. .991 1. .00 0. .00 XXXX3623

ATOM 3624 CA TYR B 111 11. .377 54. .418 58. .924 1. .00 0. .00 XXXX3624

ATOM 3625 C TYR B 111 11. .528 52. .930 59. .238 1. .00 0. .00 XXXX3625

ATOM 3626 O TYR B 111 12. .179 52. .565 60. .215 1. .00 0. .00 XXXX3626

ATOM 3627 CB TYR B 111 12. .741 55. .092 58. .745 1. .00 0. .00 XXXX3627

ATOM 3628 CG TYR B 111 13. .706 54. .413 57. .811 1. .00 0. .00 XXXX3628

ATOM 3629 CD1 TYR B 111 14. .855 53. .808 58. .300 1. .00 0. .00 XXXX3629

ATOM 3630 CD2 TYR B 111 13. .488 54. .398 56. .440 1. .00 0. .00 XXXX3630

ATOM 3631 CE1 TYR B 111 15. .754 53. .198 57. .456 1. .00 0. .00 XXXX3631

ATOM 3632 CE2 TYR B 111 14. .383 53. .788 55. .586 1. .00 0. .00 XXXX3632

ATOM 3633 CZ TYR B 111 15. .514 53. .189 56. .101 1. .00 0. .00 XXXX3633

ATOM 3634 OH TYR B 111 16. .413 52. .576 55. .260 1. .00 0. .00 XXXX3634

ATOM 3635 N PRO B 112 10. .920 52. .065 58. .407 1. .00 0. .00 XXXX3635

ATOM 3636 CA PRO B 112 10. .791 50. .636 58. .719 1. .00 0. .00 XXXX3636

ATOM 3637 C PRO B 112 11. .853 49. .703 58. .126 1. .00 0. .00 XXXX3637

ATOM 3638 O PRO B 112 11. .687 48. .489 58. .241 1. .00 0. .00 XXXX3638

ATOM 3639 CB PRO B 112 9. .426 50. .297 58. .121 1. .00 0. .00 XXXX3639

ATOM 3640 CG PRO B 112 9. .363 51. .158 56. .900 1. .00 0. .00 XXXX3640

ATOM 3641 CD PRO B 112 10. .102 52. .441 57. .241 1. .00 0. .00 XXXX3641

ATOM 3642 N VAL B 113 12. .912 50. .228 57. .519 1. .00 0. .00 XXXX3642

ATOM 3643 CA VAL B 113 13. .821 49. .365 56. .766 1. .00 0. .00 XXXX3643

ATOM 3644 C VAL B 113 15. .228 49. .237 57. .358 1. .00 0. .00 XXXX3644

ATOM 3645 O VAL B 113 15. .803 50. .209 57. .850 1. .00 0. .00 XXXX3645

ATOM 3646 CB VAL B 113 13. .957 49. .852 55. .305 1. .00 0. .00 XXXX3646

ATOM 3647 CGI VAL B 113 14. .866 48. .921 54. .516 1. .00 0. .00 XXXX3647

ATOM 3648 CG2 VAL B 113 12. .585 49. .950 54. .645 1. .00 0. .00 XXXX3648

ATOM 3649 N GLN B 114 15. .759 48. .016 57. .318 1. .00 0. .00 XXXX3649

ATOM 3650 CA GLN B 114 17. .159 47. .747 57. .646 1. .00 0. .00 XXXX3650

ATOM 3651 C GLN B 114 18. .092 48. .722 56. .929 1. .00 0. .00 XXXX3651

ATOM 3652 O GLN B 114 17. .813 49. .133 55. .805 1. .00 0. .00 XXXX3652

ATOM 3653 CB GLN B 114 17. .518 46. .302 57. .281 1. .00 0. .00 XXXX3653

ATOM 3654 CG GLN B 114 17. .214 45. .919 55. .832 1. .00 0. .00 XXXX3654

ATOM 3655 CD GLN B 114 18. .267 46. .406 54. .849 1. .00 0. .00 XXXX3655

ATOM 3656 OE1 GLN B 114 17. .958 46. .739 53. .704 1. .00 0. .00 XXXX3656

ATOM 3657 NE2 GLN B 114 19. .519 46. .443 55. .292 1. .00 0. .00 XXXX3657

ATOM 3658 N TYR B 115 19. .194 49. .098 57. .570 1. .00 0. .00 XXXX3658

ATOM 3659 CA TYR B 115 20. .104 50. .051 56. .943 1. .00 0. .00 XXXX3659

ATOM 3660 C TYR B 115 21. .504 50. .055 57. .558 1. .00 0. .00 XXXX3660

ATOM 3661 O TYR B 115 21. .818 49. .245 58. .432 1. .00 0. .00 XXXX3661 Attorney Docket No. 35327-522001 WO

ATOM 3662 CB TYR B 115 19. .494 51. .457 56. .991 1. .00 0. .00 XXXX3662

ATOM 3663 CG TYR B 115 19. .752 52. .222 58. .268 1. .00 0. .00 XXXX3663

ATOM 3664 CD1 TYR B 115 19. .256 51. .775 59. .486 1. .00 0. .00 XXXX3664

ATOM 3665 CD2 TYR B 115 20. .471 53. .409 58. .250 1. .00 0. .00 XXXX3665

ATOM 3666 CE1 TYR B 115 19. .486 52. .481 60. .653 1. .00 0. .00 XXXX3666

ATOM 3667 CE2 TYR B 115 20. .702 54. .122 59. .408 1. .00 0. .00 XXXX3667

ATOM 3668 CZ TYR B 115 20. .210 53. .656 60. .606 1. .00 0. .00 XXXX3668

ATOM 3669 OH TYR B 115 20. .447 54. .369 61. .758 1. .00 0. .00 XXXX3669

ATOM 3670 N GLU B 116 22. .334 50. .981 57. .088 1. .00 0. .00 XXXX3670

ATOM 3671 CA GLU B 116 23. .764 50. .973 57. .381 1. .00 0. .00 XXXX3671

ATOM 3672 C GLU B 116 24. .129 51. .555 58. .743 1. .00 0. .00 XXXX3672

ATOM 3673 O GLU B 116 25. .265 51. .411 59. .196 1. .00 0. .00 XXXX3673

ATOM 3674 CB GLU B 116 24. .516 51. .739 56. .289 1. .00 0. .00 XXXX3674

ATOM 3675 CG GLU B 116 24. .287 53. .248 56. .307 1. .00 0. .00 XXXX3675

ATOM 3676 CD GLU B 116 22. .955 53. .655 55. .701 1. .00 0. .00 XXXX3676

ATOM 3677 OE1 GLU B 116 22. .259 52. .781 55. .143 1. .00 0. .00 XXXX3677

ATOM 3678 OE2 GLU B 116 22. .609 54. .854 55. .773 1. .00 0. .00 XXXX3678

ATOM 3679 N GLY B 117 23. .179 52. .223 59. .386 1. .00 0. .00 XXXX3679

ATOM 3680 CA GLY B 117 23. .457 52. .888 60. .645 1. .00 0. .00 XXXX3680

ATOM 3681 C GLY B 117 24. .273 54. .147 60. .426 1. .00 0. .00 XXXX3681

ATOM 3682 O GLY B 117 24. .104 54. .833 59. .418 1. .00 0. .00 XXXX3682

ATOM 3683 N LEU B 118 25. .167 54. .443 61. .366 1. .00 0. .00 XXXX3683

ATOM 3684 CA LEU B 118 26. .009 55. .632 61. .281 1. .00 0. .00 XXXX3684

ATOM 3685 C LEU B 118 25. .147 56. .880 61. .161 1. .00 0. .00 XXXX3685

ATOM 3686 O LEU B 118 25. .533 57. .865 60. .531 1. .00 0. .00 XXXX3686

ATOM 3687 CB LEU B 118 26. .973 55. .530 60. .097 1. .00 0. .00 XXXX3687

ATOM 3688 CG LEU B 118 27. .926 54. .332 60. .122 1. .00 0. .00 XXXX3688

ATOM 3689 CD1 LEU B 118 28. .918 54. .399 58. .971 1. .00 0. .00 XXXX3689

ATOM 3690 CD2 LEU B 118 28. .651 54. .246 61. .459 1. .00 0. .00 XXXX3690

ATOM 3691 N GLU B 119 23. .974 56. .824 61. .779 1. .00 0. .00 XXXX3691

ATOM 3692 CA GLU B 119 23. .013 57. .913 61. .725 1. .00 0. .00 XXXX3692

ATOM 3693 C GLU B 119 22. .112 57. .862 62. .953 1. .00 0. .00 XXXX3693

ATOM 3694 O GLU B 119 21. .871 56. .791 63. .507 1. .00 0. .00 XXXX3694

ATOM 3695 CB GLU B 119 22. .181 57. .826 60. .443 1. .00 0. .00 XXXX3695

ATOM 3696 CG GLU B 119 21. .226 58. .985 60. .220 1. .00 0. .00 XXXX3696

ATOM 3697 CD GLU B 119 20. .300 58. .748 59. .039 1. .00 0. .00 XXXX3697

ATOM 3698 OE1 GLU B 119 20. .785 58. .781 57. .887 1. .00 0. .00 XXXX3698

ATOM 3699 OE2 GLU B 119 19. .089 58. .528 59. .262 1. .00 0. .00 XXXX3699

ATOM 3700 N SER B 120 21. .618 59. .020 63. .376 1. .00 0. .00 XXXX3700

ATOM 3701 CA SER B 120 20. .656 59. .075 64. .470 1. .00 0. .00 XXXX3701

ATOM 3702 C SER B 120 19. .969 60. .433 64. .527 1. .00 0. .00 XXXX3702

ATOM 3703 O SER B 120 20. .260 61. .251 65. .399 1. .00 0. .00 XXXX3703

ATOM 3704 CB SER B 120 21. .338 58. .774 65. .807 1. .00 0. .00 XXXX3704

ATOM 3705 OG SER B 120 21. .526 57. .380 65. .982 1. .00 0. .00 XXXX3705

ATOM 3706 N SER B 121 19. .056 60. .662 63. .590 1. .00 0. .00 XXXX3706

ATOM 3707 CA SER B 121 18. .291 61. .902 63. .545 1. .00 0. .00 XXXX3707

ATOM 3708 C SER B 121 17. .262 61. .954 64. .668 1. .00 0. .00 XXXX3708

ATOM 3709 O SER B 121 16. .546 60. .982 64. .907 1. .00 0. .00 XXXX3709

ATOM 3710 CB SER B 121 17. .598 62. .054 62. .189 1. .00 0. .00 XXXX3710

ATOM 3711 OG SER B 121 16. .687 63. .138 62. .194 1. .00 0. .00 XXXX3711

ATOM 3712 N PRO B 122 17. .184 63. .095 65. .365 1. .00 0. .00 XXXX3712

ATOM 3713 CA PRO B 122 16. .168 63. .286 66. .405 1. .00 0. .00 XXXX3713

ATOM 3714 C PRO B 122 14. .755 63. .300 65. .825 1. .00 0. .00 XXXX3714

ATOM 3715 O PRO B 122 13. .778 63. .218 66. .569 1. .00 0. .00 XXXX3715

ATOM 3716 CB PRO B 122 16. .529 64. .650 67. .001 1. .00 0. .00 XXXX3716

ATOM 3717 CG PRO B 122 17. .242 65. .361 65. .895 1. .00 0. .00 XXXX3717

ATOM 3718 CD PRO B 122 18. .021 64. .293 65. .182 1. .00 0. .00 XXXX3718

ATOM 3719 N ASN B 123 14. .658 63. .402 64. .503 1. .00 0. .00 XXXX3719

ATOM 3720 CA ASN B 123 13. .367 63. .461 63. .828 1. .00 0. .00 XXXX3720

ATOM 3721 C ASN B 123 13. .046 62. .189 63. .051 1. .00 0. .00 XXXX3721

ATOM 3722 O ASN B 123 12. .147 62. .175 62. .210 1. .00 0. .00 XXXX3722

ATOM 3723 CB ASN B 123 13. .323 64. .667 62. .890 1. .00 0. .00 XXXX3723

ATOM 3724 CG ASN B 123 13. .425 65. .982 63. .636 1. .00 0. .00 XXXX3724

ATOM 3725 OD1 ASN B 123 14. .515 66. .527 63. .808 1. .00 0. .00 XXXX3725

ATOM 3726 ND2 ASN B 123 12. .287 66. .496 64. .088 1. .00 0. .00 XXXX3726

ATOM 3727 N ILE B 124 13. .783 61. .121 63. .335 1. .00 0. .00 XXXX3727

ATOM 3728 CA ILE B 124 13. .503 59. .828 62. .729 1. .00 0. .00 XXXX3728 Attorney Docket No. 35327-522001 WO

ATOM 3729 C ILE B 124 13. .431 58. .728 63. .777 1. .00 0. .00 XXXX3729

ATOM 3730 O ILE B 124 14. .280 58. .645 64. .662 1. .00 0. .00 XXXX3730

ATOM 3731 CB ILE B 124 14. .569 59. .437 61. .684 1. .00 0. .00 XXXX3731

ATOM 3732 CGI ILE B 124 14. .648 60. .485 60. .574 1. .00 0. .00 XXXX3732

ATOM 3733 CG2 ILE B 124 14. .259 58. .067 61. .093 1. .00 0. .00 XXXX3733

ATOM 3734 CD1 ILE B 124 15. .661 60. .150 59. .501 1. .00 0. .00 XXXX3734

ATOM 3735 N PHE B 125 12. .408 57. .886 63. .673 1. .00 0. .00 XXXX3735

ATOM 3736 CA PHE B 125 12. .351 56. .666 64. .465 1. .00 0. .00 XXXX3736

ATOM 3737 C PHE B 125 12. .614 55. .467 63. .563 1. .00 0. .00 XXXX3737

ATOM 3738 O PHE B 125 11. .947 55. .281 62. .544 1. .00 0. .00 XXXX3738

ATOM 3739 CB PHE B 125 11. .006 56. .539 65. .185 1. .00 0. .00 XXXX3739

ATOM 3740 CG PHE B 125 10. .911 57. .382 66. .424 1. .00 0. .00 XXXX3740

ATOM 3741 CD1 PHE B 125 11. .253 56. .858 67. .661 1. .00 0. .00 XXXX3741

ATOM 3742 CD2 PHE B 125 10. .508 58. .705 66. .351 1. .00 0. .00 XXXX3742

ATOM 3743 CE1 PHE B 125 11. .182 57. .633 68. .802 1. .00 0. .00 XXXX3743

ATOM 3744 CE2 PHE B 125 10. .433 59. .484 67. .490 1. .00 0. .00 XXXX3744

ATOM 3745 CZ PHE B 125 10. .771 58. .949 68. .717 1. .00 0. .00 XXXX3745

ATOM 3746 N TYR B 126 13. .595 54. .660 63. .949 1. .00 0. .00 XXXX3746

ATOM 3747 CA TYR B 126 14. .100 53. .592 63. .098 1. .00 0. .00 XXXX3747

ATOM 3748 C TYR B 126 13. .552 52. .245 63. .543 1. .00 0. .00 XXXX3748

ATOM 3749 O TYR B 126 13. .964 51. .706 64. .571 1. .00 0. .00 XXXX3749

ATOM 3750 CB TYR B 126 15. .632 53. .563 63. .125 1. .00 0. .00 XXXX3750

ATOM 3751 CG TYR B 126 16. .299 54. .873 62. .755 1. .00 0. .00 XXXX3751

ATOM 3752 CD1 TYR B 126 16. .925 55. .034 61. .525 1. .00 0. .00 XXXX3752

ATOM 3753 CD2 TYR B 126 16. .319 55. .942 63. .642 1. .00 0. .00 XXXX3753

ATOM 3754 CE1 TYR B 126 17. .545 56. .226 61. .186 1. .00 0. .00 XXXX3754

ATOM 3755 CE2 TYR B 126 16. .933 57. .140 63. .310 1. .00 0. .00 XXXX3755

ATOM 3756 CZ TYR B 126 17. .546 57. .276 62. .081 1. .00 0. .00 XXXX3756

ATOM 3757 OH TYR B 126 18. .161 58. .462 61. .743 1. .00 0. .00 XXXX3757

ATOM 3758 N MET B 127 12. .622 51. .702 62. .764 1. .00 0. .00 XXXX3758

ATOM 3759 CA MET B 127 11. .993 50. .433 63. .100 1. .00 0. .00 XXXX3759

ATOM 3760 C MET B 127 12. .739 49. .279 62. .443 1. .00 0. .00 XXXX3760

ATOM 3761 O MET B 127 12. .556 48. .119 62. .812 1. .00 0. .00 XXXX3761

ATOM 3762 CB MET B 127 10. .522 50. .427 62. .678 1. .00 0. .00 XXXX3762

ATOM 3763 CG MET B 127 9. .694 51. .555 63. .282 1. .00 0. .00 XXXX3763

ATOM 3764 SD MET B 127 9. .547 51. .471 65. .080 1. .00 0. .00 XXXX3764

ATOM 3765 CE MET B 127 10. .731 52. .720 65. .575 1. .00 0. .00 XXXX3765

ATOM 3766 N GLY B 128 13. .581 49. .605 61. .467 1. .00 0. .00 XXXX3766

ATOM 3767 CA GLY B 128 14. .389 48. .605 60. .795 1. .00 0. .00 XXXX3767

ATOM 3768 C GLY B 128 15. .712 48. .382 61. .503 1. .00 0. .00 XXXX3768

ATOM 3769 O GLY B 128 16. .139 49. .202 62. .316 1. .00 0. .00 XXXX3769

ATOM 3770 N ALA B 129 16. .361 47. .266 61. .188 1. .00 0. .00 XXXX3770

ATOM 3771 CA ALA B 129 17. .595 46. .867 61. .860 1. .00 0. .00 XXXX3771

ATOM 3772 C ALA B 129 18. .725 47. .880 61. .705 1. .00 0. .00 XXXX3772

ATOM 3773 O ALA B 129 18. .936 48. .434 60. .625 1. .00 0. .00 XXXX3773

ATOM 3774 CB ALA B 129 18. .048 45. .509 61. .345 1. .00 0. .00 XXXX3774

ATOM 3775 N ALA B 130 19. .445 48. .116 62. .798 1. .00 0. .00 XXXX3775

ATOM 3776 CA ALA B 130 20. .760 48. .739 62. .731 1. .00 0. .00 XXXX3776

ATOM 3777 C ALA B 130 21. .767 47. .660 62. .354 1. .00 0. .00 XXXX3777

ATOM 3778 O ALA B 130 21. .464 46. .471 62. .462 1. .00 0. .00 XXXX3778

ATOM 3779 CB ALA B 130 21. .124 49. .391 64. .053 1. .00 0. .00 XXXX3779

ATOM 3780 N PRO B 131 22. .967 48. .063 61. .912 1. .00 0. .00 XXXX3780

ATOM 3781 CA PRO B 131 23. .939 47. .089 61. .397 1. .00 0. .00 XXXX3781

ATOM 3782 C PRO B 131 24. .337 46. .015 62. .415 1. .00 0. .00 XXXX3782

ATOM 3783 O PRO B 131 24. .593 44. .876 62. .022 1. .00 0. .00 XXXX3783

ATOM 3784 CB PRO B 131 25. .146 47. .962 61. .024 1. .00 0. .00 XXXX3784

ATOM 3785 CG PRO B 131 24. .959 49. .239 61. .784 1. .00 0. .00 XXXX3785

ATOM 3786 CD PRO B 131 23. .482 49. .441 61. .868 1. .00 0. .00 XXXX3786

ATOM 3787 N ASN B 132 24. .377 46. .363 63. .697 1. .00 0. .00 XXXX3787

ATOM 3788 CA ASN B 132 24. .692 45. .379 64. .727 1. .00 0. .00 XXXX3788

ATOM 3789 C ASN B 132 23. .545 44. .384 64. .898 1. .00 0. .00 XXXX3789

ATOM 3790 O ASN B 132 23. .702 43. .346 65. .541 1. .00 0. .00 XXXX3790

ATOM 3791 CB ASN B 132 25. .012 46. .060 66. .062 1. .00 0. .00 XXXX3791

ATOM 3792 CG ASN B 132 23. .784 46. .641 66. .737 1. .00 0. .00 XXXX3792

ATOM 3793 OD1 ASN B 132 23. .046 47. .428 66. .144 1. .00 0. .00 XXXX3793

ATOM 3794 ND2 ASN B 132 23. .562 46. .255 67. .989 1. .00 0. .00 XXXX3794

ATOM 3795 N GLN B 133 22. .394 44. .708 64. .316 1. .00 0. .00 XXXX3795 Attorney Docket No. 35327-522001 WO

ATOM 3796 CA GLN B 133 21. .219 43. .844 64. .393 1. .00 0. .00 XXXX3796

ATOM 3797 C GLN B 133 20. .970 43. .065 63. .101 1. .00 0. .00 XXXX3797

ATOM 3798 O GLN B 133 19. .963 42. .369 62. .980 1. .00 0. .00 XXXX3798

ATOM 3799 CB GLN B 133 19. .975 44. .667 64. .739 1. .00 0. .00 XXXX3799

ATOM 3800 CG GLN B 133 20. .070 45. .432 66. .049 1. .00 0. .00 XXXX3800

ATOM 3801 CD GLN B 133 18. .873 46. .335 66. .281 1. .00 0. .00 XXXX3801

ATOM 3802 OE1 GLN B 133 18. .424 47. .036 65. .373 1. .00 0. .00 XXXX3802

ATOM 3803 NE2 GLN B 133 18. .344 46. .318 67. .499 1. .00 0. .00 XXXX3803

ATOM 3804 N GLN B 134 21. .875 43. .186 62. .133 1. .00 0. .00 XXXX3804

ATOM 3805 CA GLN B 134 21. .719 42. .459 60. .874 1. .00 0. .00 XXXX3805

ATOM 3806 C GLN B 134 23. .046 42. .143 60. .184 1. .00 0. .00 XXXX3806

ATOM 3807 O GLN B 134 23. .529 41. .013 60. .245 1. .00 0. .00 XXXX3807

ATOM 3808 CB GLN B 134 20. .816 43. .243 59. .914 1. .00 0. .00 XXXX3808

ATOM 3809 CG GLN B 134 20. .490 42. .490 58. .629 1. .00 0. .00 XXXX3809

ATOM 3810 CD GLN B 134 19. .842 43. .368 57. .573 1. .00 0. .00 XXXX3810

ATOM 3811 OE1 GLN B 134 20. .260 44. .504 57. .348 1. .00 0. .00 XXXX3811

ATOM 3812 NE2 GLN B 134 18. .821 42. .839 56. .911 1. .00 0. .00 XXXX3812

ATOM 3813 N ILE B 135 23. .628 43. .140 59. .526 1. .00 0. .00 XXXX3813

ATOM 3814 CA ILE B 135 24. .814 42. .927 58. .696 1. .00 0. .00 XXXX3814

ATOM 3815 C ILE B 135 26. .012 42. .378 59. .474 1. .00 0. .00 XXXX3815

ATOM 3816 O ILE B 135 26. .711 41. .483 58. .994 1. .00 0. .00 XXXX3816

ATOM 3817 CB ILE B 135 25. .241 44. .228 57. .993 1. .00 0. .00 XXXX3817

ATOM 3818 CGI ILE B 135 24. .264 44. .566 56. .865 1. .00 0. .00 XXXX3818

ATOM 3819 CG2 ILE B 135 26. .645 44. .091 57. .432 1. .00 0. .00 XXXX3819

ATOM 3820 CD1 ILE B 135 24. .481 45. .936 56. .261 1. .00 0. .00 XXXX3820

ATOM 3821 N VAL B 136 26. .251 42. .912 60. .667 1. .00 0. .00 XXXX3821

ATOM 3822 CA VAL B 136 27. .402 42. .492 61. .460 1. .00 0. .00 XXXX3822

ATOM 3823 C VAL B 136 27. .282 41. .023 61. .867 1. .00 0. .00 XXXX3823

ATOM 3824 O VAL B 136 28. .204 40. .239 61. .638 1. .00 0. .00 XXXX3824

ATOM 3825 CB VAL B 136 27. .579 43. .362 62. .721 1. .00 0. .00 XXXX3825

ATOM 3826 CGI VAL B 136 28. .604 42. .739 63. .657 1. .00 0. .00 XXXX3826

ATOM 3827 CG2 VAL B 136 27. .997 44. .772 62. .334 1. .00 0. .00 XXXX3827

ATOM 3828 N PRO B 137 26. .146 40. .643 62. .473 1. .00 0. .00 XXXX3828

ATOM 3829 CA PRO B 137 25. .919 39. .234 62. .819 1. .00 0. .00 XXXX3829

ATOM 3830 C PRO B 137 25. .910 38. .319 61. .593 1. .00 0. .00 XXXX3830

ATOM 3831 O PRO B 137 26. .291 37. .154 61. .696 1. .00 0. .00 XXXX3831

ATOM 3832 CB PRO B 137 24. .541 39. .255 63. .490 1. .00 0. .00 XXXX3832

ATOM 3833 CG PRO B 137 24. .382 40. .655 63. .986 1. .00 0. .00 XXXX3833

ATOM 3834 CD PRO B 137 25. .062 41. .512 62. .965 1. .00 0. .00 XXXX3834

ATOM 3835 N ALA B 138 25. .480 38. .847 60. .451 1. .00 0. .00 XXXX3835

ATOM 3836 CA ALA B 138 25. .478 38. .083 59. .206 1. .00 0. .00 XXXX3836

ATOM 3837 C ALA B 138 26. .893 37. .663 58. .820 1. .00 0. .00 XXXX3837

ATOM 3838 O ALA B 138 27. .143 36. .498 58. .511 1. .00 0. .00 XXXX3838

ATOM 3839 CB ALA B 138 24. .840 38. .894 58. .086 1. .00 0. .00 XXXX3839

ATOM 3840 N VAL B 139 27. .811 38. .623 58. .844 1. .00 0. .00 XXXX3840

ATOM 3841 CA VAL B 139 29. .211 38. .369 58. .519 1. .00 0. .00 XXXX3841

ATOM 3842 C VAL B 139 29. .829 37. .354 59. .478 1. .00 0. .00 XXXX3842

ATOM 3843 O VAL B 139 30. .526 36. .431 59. .056 1. .00 0. .00 XXXX3843

ATOM 3844 CB VAL B 139 30. .041 39. .667 58. .558 1. .00 0. .00 XXXX3844

ATOM 3845 CGI VAL B 139 31. .524 39. .356 58. .393 1. .00 0. .00 XXXX3845

ATOM 3846 CG2 VAL B 139 29. .566 40. .633 57. .481 1. .00 0. .00 XXXX3846

ATOM 3847 N LYS B 140 29. .567 37. .535 60. .769 1. .00 0. .00 XXXX3847

ATOM 3848 CA LYS B 140 30. .119 36. .663 61. .801 1. .00 0. .00 XXXX3848

ATOM 3849 C LYS B 140 29. .665 35. .213 61. .641 1. .00 0. .00 XXXX3849

ATOM 3850 O LYS B 140 30. .478 34. .291 61. .709 1. .00 0. .00 XXXX3850

ATOM 3851 CB LYS B 140 29. .727 37. .177 63. .188 1. .00 0. .00 XXXX3851

ATOM 3852 CG LYS B 140 30. .349 36. .403 64. .338 1. .00 0. .00 XXXX3852

ATOM 3853 CD LYS B 140 31. .839 36. .675 64. .451 1. .00 0. .00 XXXX3853

ATOM 3854 CE LYS B 140 32. .464 35. .825 65. .543 1. .00 0. .00 XXXX3854

ATOM 3855 NZ LYS B 140 31. .685 35. .903 66. .809 1. .00 0. .00 XXXX3855

ATOM 3856 N TRP B 141 28. .366 35. .016 61. .432 1. .00 0. .00 XXXX3856

ATOM 3857 CA TRP B 141 27. .812 33. .677 61. .260 1. .00 0. .00 XXXX3857

ATOM 3858 C TRP B 141 28. .388 33. .010 60. .017 1. .00 0. .00 XXXX3858

ATOM 3859 O TRP B 141 28. .736 31. .829 60. .038 1. .00 0. .00 XXXX3859

ATOM 3860 CB TRP B 141 26. .285 33. .732 61. .172 1. .00 0. .00 XXXX3860

ATOM 3861 CG TRP B 141 25. .639 32. .386 61. .007 1. .00 0. .00 XXXX3861

ATOM 3862 CD1 TRP B 141 25. .291 31. .515 61. .999 1. .00 0. .00 XXXX3862 Attorney Docket No. 35327-522001 WO

ATOM 3863 CD2 TRP B 141 25. .260 31. .761 59. .774 1. .00 0. .00 XXXX3863

ATOM 3864 NE1 TRP B 141 24. .721 30. .386 61. .461 1. .00 0. .00 XXXX3864

ATOM 3865 CE2 TRP B 141 24. .691 30. .512 60. .097 1. .00 0. .00 XXXX3865

ATOM 3866 CE3 TRP B 141 25. .349 32. .134 58. .429 1. .00 0. .00 XXXX3866

ATOM 3867 CZ2 TRP B 141 24. .213 29. .636 59. .124 1. .00 0. .00 XXXX3867

ATOM 3868 CZ3 TRP B 141 24. .874 31. .263 57. .466 1. .00 0. .00 XXXX3868

ATOM 3869 CH2 TRP B 141 24. .313 30. .029 57. .818 1. .00 0. .00 XXXX3869

ATOM 3870 N LEU B 142 28. .481 33. .778 58. .936 1. .00 0. .00 XXXX3870

ATOM 3871 CA LEU B 142 29. .085 33. .303 57. .696 1. .00 0. .00 XXXX3871

ATOM 3872 C LEU B 142 30. .530 32. .870 57. .922 1. .00 0. .00 XXXX3872

ATOM 3873 O LEU B 142 30. .947 31. .798 57. .482 1. .00 0. .00 XXXX3873

ATOM 3874 CB LEU B 142 29. .019 34. .389 56. .622 1. .00 0. .00 XXXX3874

ATOM 3875 CG LEU B 142 27. .645 34. .615 55. .987 1. .00 0. .00 XXXX3875

ATOM 3876 CD1 LEU B 142 27. .671 35. .819 55. .058 1. .00 0. .00 XXXX3876

ATOM 3877 CD2 LEU B 142 27. .199 33. .366 55. .242 1. .00 0. .00 XXXX3877

ATOM 3878 N PHE B 143 31. .288 33. .714 58. .615 1. .00 0. .00 XXXX3878

ATOM 3879 CA PHE B 143 32. .697 33. .447 58. .877 1. .00 0. .00 XXXX3879

ATOM 3880 C PHE B 143 32. .878 32. .211 59. .753 1. .00 0. .00 XXXX3880

ATOM 3881 O PHE B 143 33. .718 31. .358 59. .468 1. .00 0. .00 XXXX3881

ATOM 3882 CB PHE B 143 33. .356 34. .660 59. .538 1. .00 0. .00 XXXX3882

ATOM 3883 CG PHE B 143 34. .837 34. .513 59. .733 1. .00 0. .00 XXXX3883

ATOM 3884 CD1 PHE B 143 35. .712 34. .736 58. .684 1. .00 0. .00 XXXX3884

ATOM 3885 CD2 PHE B 143 35. .354 34. .151 60. .966 1. .00 0. .00 XXXX3885

ATOM 3886 CE1 PHE B 143 37. .077 34. .600 58. .860 1. .00 0. .00 XXXX3886

ATOM 3887 CE2 PHE B 143 36. .718 34. .013 61. .149 1. .00 0. .00 XXXX3887

ATOM 3888 CZ PHE B 143 37. .580 34. .238 60. .094 1. .00 0. .00 XXXX3888

ATOM 3889 N ASP B 144 32. .088 32. .122 60. .820 1. .00 0. .00 XXXX3889

ATOM 3890 CA ASP B 144 32. .164 30. .991 61. .740 1. .00 0. .00 XXXX3890

ATOM 3891 C ASP B 144 31. .722 29. .689 61. .080 1. .00 0. .00 XXXX3891

ATOM 3892 O ASP B 144 31. .968 28. .603 61. .606 1. .00 0. .00 XXXX3892

ATOM 3893 CB ASP B 144 31. .314 31. .256 62. .985 1. .00 0. .00 XXXX3893

ATOM 3894 CG ASP B 144 31. .928 32. .300 63. .894 1. .00 0. .00 XXXX3894

ATOM 3895 OD1 ASP B 144 33. .078 32. .707 63. .628 1. .00 0. .00 XXXX3895

ATOM 3896 OD2 ASP B 144 31. .268 32. .710 64. .870 1. .00 0. .00 XXXX3896

ATOM 3897 N ASN B 145 31. .073 29. .803 59. .927 1. .00 0. .00 XXXX3897

ATOM 3898 CA ASN B 145 30. .641 28. .627 59. .183 1. .00 0. .00 XXXX3898

ATOM 3899 C ASN B 145 31. .449 28. .399 57. .908 1. .00 0. .00 XXXX3899

ATOM 3900 O ASN B 145 30. .962 27. .791 56. .955 1. .00 0. .00 XXXX3900

ATOM 3901 CB ASN B 145 29. .152 28. .735 58. .851 1. .00 0. .00 XXXX3901

ATOM 3902 CG ASN B 145 28. .270 28. .450 60. .051 1. .00 0. .00 XXXX3902

ATOM 3903 OD1 ASN B 145 27. .927 27. .299 60. .321 1. .00 0. .00 XXXX3903

ATOM 3904 ND2 ASN B 145 27. .906 29. .497 60. .784 1. .00 0. .00 XXXX3904

ATOM 3905 N GLY B 146 32. .683 28. .892 57. .895 1. .00 0. .00 XXXX3905

ATOM 3906 CA GLY B 146 33. .633 28. .533 56. .858 1. .00 0. .00 XXXX3906

ATOM 3907 C GLY B 146 33. .742 29. .467 55. .666 1. .00 0. .00 XXXX3907

ATOM 3908 O GLY B 146 34. .570 29. .244 54. .783 1. .00 0. .00 XXXX3908

ATOM 3909 N LYS B 147 32. .919 30. .510 55. .630 1. .00 0. .00 XXXX3909

ATOM 3910 CA LYS B 147 32. .981 31. .469 54. .530 1. .00 0. .00 XXXX3910

ATOM 3911 C LYS B 147 34. .005 32. .554 54. .839 1. .00 0. .00 XXXX3911

ATOM 3912 O LYS B 147 33. .781 33. .409 55. .697 1. .00 0. .00 XXXX3912

ATOM 3913 CB LYS B 147 31. .607 32. .089 54. .270 1. .00 0. .00 XXXX3913

ATOM 3914 CG LYS B 147 30. .481 31. .073 54. .151 1. .00 0. .00 XXXX3914

ATOM 3915 CD LYS B 147 30. .790 30. .001 53. .114 1. .00 0. .00 XXXX3915

ATOM 3916 CE LYS B 147 29. .769 28. .871 53. .164 1. .00 0. .00 XXXX3916

ATOM 3917 NZ LYS B 147 30. .036 27. .836 52. .127 1. .00 0. .00 XXXX3917

ATOM 3918 N LYS B 148 35. .127 32. .516 54. .127 1. .00 0. .00 XXXX3918

ATOM 3919 CA LYS B 148 36. .248 33. .402 54. .416 1. .00 0. .00 XXXX3919

ATOM 3920 C LYS B 148 36. .470 34. .437 53. .319 1. .00 0. .00 XXXX3920

ATOM 3921 O LYS B 148 36. .995 35. .521 53. .574 1. .00 0. .00 XXXX3921

ATOM 3922 CB LYS B 148 37. .525 32. .585 54. .615 1. .00 0. .00 XXXX3922

ATOM 3923 CG LYS B 148 37. .357 31. .400 55. .549 1. .00 0. .00 XXXX3923

ATOM 3924 CD LYS B 148 36. .948 31. .851 56. .939 1. .00 0. .00 XXXX3924

ATOM 3925 CE LYS B 148 36. .695 30. .662 57. .846 1. .00 0. .00 XXXX3925

ATOM 3926 NZ LYS B 148 36. .427 31. .080 59. .248 1. .00 0. .00 XXXX3926

ATOM 3927 N ARG B 149 36. .067 34. .094 52. .100 1. .00 0. .00 XXXX3927

ATOM 3928 CA ARG B 149 36. .325 34. .933 50. .936 1. .00 0. .00 XXXX3928

ATOM 3929 C ARG B 149 35. .030 35. .513 50. .377 1. .00 0. .00 XXXX3929 Attorney Docket No. 35327-522001 WO

ATOM 3930 O ARG B 149 34. .277 34. .829 49. .685 1. .00 0. .00 XXXX3930

ATOM 3931 CB ARG B 149 37. .059 34. .133 49. .859 1. .00 0. .00 XXXX3931

ATOM 3932 CG ARG B 149 38. .384 33. .549 50. .326 1. .00 0. .00 XXXX3932

ATOM 3933 CD ARG B 149 38. .876 32. .470 49. .376 1. .00 0. .00 XXXX3933

ATOM 3934 NE ARG B 149 38. .977 32. .970 48. .010 1. .00 0. .00 XXXX3934

ATOM 3935 CZ ARG B 149 38. .121 32. .664 47. .042 1. .00 0. .00 XXXX3935

ATOM 3936 NH1 ARG B 149 37. .098 31. .856 47. .291 1. .00 0. .00 XXXX3936

ATOM 3937 NH2 ARG B 149 38. .284 33. .166 45. .824 1. .00 0. .00 XXXX3937

ATOM 3938 N PHE B 150 34. .782 36. .781 50. .688 1. .00 0. .00 XXXX3938

ATOM 3939 CA PHE B 150 33. .527 37. .437 50. .338 1. .00 0. .00 XXXX3939

ATOM 3940 C PHE B 150 33. .587 38. .141 48. .989 1. .00 0. .00 XXXX3940

ATOM 3941 O PHE B 150 34. .566 38. .816 48. .672 1. .00 0. .00 XXXX3941

ATOM 3942 CB PHE B 150 33. .141 38. .461 51. .411 1. .00 0. .00 XXXX3942

ATOM 3943 CG PHE B 150 32. .588 37. .855 52. .671 1. .00 0. .00 XXXX3943

ATOM 3944 CD1 PHE B 150 33. .199 36. .764 53. .264 1. .00 0. .00 XXXX3944

ATOM 3945 CD2 PHE B 150 31. .455 38. .387 53. .265 1. .00 0. .00 XXXX3945

ATOM 3946 CE1 PHE B 150 32. .689 36. .212 54. .424 1. .00 0. .00 XXXX3946

ATOM 3947 CE2 PHE B 150 30. .940 37. .840 54. .425 1. .00 0. .00 XXXX3947

ATOM 3948 CZ PHE B 150 31. .558 36. .751 55. .005 1. .00 0. .00 XXXX3948

ATOM 3949 N TYR B 151 32. .532 37. .979 48. .197 1. .00 0. .00 XXXX3949

ATOM 3950 CA TYR B 151 32. .335 38. .803 47. .012 1. .00 0. .00 XXXX3950

ATOM 3951 C TYR B 151 31. .178 39. .756 47. .281 1. .00 0. .00 XXXX3951

ATOM 3952 O TYR B 151 30. .052 39. .322 47. .524 1. .00 0. .00 XXXX3952

ATOM 3953 CB TYR B 151 32. .053 37. .952 45. .772 1. .00 0. .00 XXXX3953

ATOM 3954 CG TYR B 151 32. .293 38. .688 44. .469 1. .00 0. .00 XXXX3954

ATOM 3955 CD1 TYR B 151 33. .388 38. .385 43. .669 1. .00 0. .00 XXXX3955

ATOM 3956 CD2 TYR B 151 31. .434 39. .695 44. .048 1. .00 0. .00 XXXX3956

ATOM 3957 CE1 TYR B 151 33. .615 39. .059 42. .480 1. .00 0. .00 XXXX3957

ATOM 3958 CE2 TYR B 151 31. .653 40. .375 42. .862 1. .00 0. .00 XXXX3958

ATOM 3959 CZ TYR B 151 32. .744 40. .053 42. .082 1. .00 0. .00 XXXX3959

ATOM 3960 OH TYR B 151 32. .962 40. .729 40. .902 1. .00 0. .00 XXXX3960

ATOM 3961 N LEU B 152 31. .459 41. .053 47. .245 1. .00 0. .00 XXXX3961

ATOM 3962 CA LEU B 152 30. .449 42. .051 47. .574 1. .00 0. .00 XXXX3962

ATOM 3963 C LEU B 152 29. .756 42. .595 46. .330 1. .00 0. .00 XXXX3963

ATOM 3964 O LEU B 152 30. .408 43. .059 45. .395 1. .00 0. .00 XXXX3964

ATOM 3965 CB LEU B 152 31. .078 43. .200 48. .365 1. .00 0. .00 XXXX3965

ATOM 3966 CG LEU B 152 31. .914 42. .788 49. .581 1. .00 0. .00 XXXX3966

ATOM 3967 CD1 LEU B 152 32. .498 44. .008 50. .276 1. .00 0. .00 XXXX3967

ATOM 3968 CD2 LEU B 152 31. .088 41. .954 50. .551 1. .00 0. .00 XXXX3968

ATOM 3969 N LEU B 153 28. .429 42. .531 46. .329 1. .00 0. .00 XXXX3969

ATOM 3970 CA LEU B 153 27. .633 43. .056 45. .226 1. .00 0. .00 XXXX3970

ATOM 3971 C LEU B 153 26. .418 43. .799 45. .766 1. .00 0. .00 XXXX3971

ATOM 3972 O LEU B 153 25. .623 43. .238 46. .521 1. .00 0. .00 XXXX3972

ATOM 3973 CB LEU B 153 27. .193 41. .932 44. .287 1. .00 0. .00 XXXX3973

ATOM 3974 CG LEU B 153 26. .175 42. .322 43. .212 1. .00 0. .00 XXXX3974

ATOM 3975 CD1 LEU B 153 26. .799 43. .273 42. .201 1. .00 0. .00 XXXX3975

ATOM 3976 CD2 LEU B 153 25. .608 41. .088 42. .521 1. .00 0. .00 XXXX3976

ATOM 3977 N GLY B 154 26. .277 45. .061 45. .377 1. .00 0. .00 XXXX3977

ATOM 3978 CA GLY B 154 25. .167 45. .876 45. .834 1. .00 0. .00 XXXX3978

ATOM 3979 C GLY B 154 24. .809 46. .980 44. .860 1. .00 0. .00 XXXX3979

ATOM 3980 O GLY B 154 25. .505 47. .193 43. .867 1. .00 0. .00 XXXX3980

ATOM 3981 N SER B 155 23. .717 47. .681 45. .147 1. .00 0. .00 XXXX3981

ATOM 3982 CA SER B 155 23. .300 48. .820 44. .339 1. .00 0. .00 XXXX3982

ATOM 3983 C SER B 155 24. .155 50. .043 44. .652 1. .00 0. .00 XXXX3983

ATOM 3984 O SER B 155 24. .662 50. .189 45. .763 1. .00 0. .00 XXXX3984

ATOM 3985 CB SER B 155 21. .819 49. .129 44. .569 1. .00 0. .00 XXXX3985

ATOM 3986 OG SER B 155 21. .014 48. .007 44. .248 1. .00 0. .00 XXXX3986

ATOM 3987 N ASP B 156 24. .318 50. .917 43. .665 1. .00 0. .00 XXXX3987

ATOM 3988 CA ASP B 156 25. .236 52. .043 43. .792 1. .00 0. .00 XXXX3988

ATOM 3989 C ASP B 156 24. .609 53. .246 44. .489 1. .00 0. .00 XXXX3989

ATOM 3990 O ASP B 156 24. .160 54. .188 43. .836 1. .00 0. .00 XXXX3990

ATOM 3991 CB ASP B 156 25. .754 52. .462 42. .413 1. .00 0. .00 XXXX3991

ATOM 3992 CG ASP B 156 27. .034 53. .273 42. .494 1. .00 0. .00 XXXX3992

ATOM 3993 OD1 ASP B 156 27. .417 53. .676 43. .613 1. .00 0. .00 XXXX3993

ATOM 3994 OD2 ASP B 156 27. .660 53. .504 41. .437 1. .00 0. .00 XXXX3994

ATOM 3995 N TYR B 157 24. .582 53. .202 45. .817 1. .00 0. .00 XXXX3995

ATOM 3996 CA TYR B 157 24. .200 54. .356 46. .623 1. .00 0. .00 XXXX3996 Attorney Docket No. 35327-522001 WO

ATOM 3997 C TYR B 157 24. .678 54. .146 48. .058 1. .00 0. .00 XXXX3997

ATOM 3998 O TYR B 157 25. .420 53. .203 48. .335 1. .00 0. .00 XXXX3998

ATOM 3999 CB TYR B 157 22. .688 54. .610 46. .560 1. .00 0. .00 XXXX3999

ATOM 4000 CG TYR B 157 21. .821 53. .574 47. .238 1. .00 0. .00 XXXX4000

ATOM 4001 CD1 TYR B 157 21. .260 53. .820 48. .484 1. .00 0. .00 XXXX4001

ATOM 4002 CD2 TYR B 157 21. .550 52. .357 46. .626 1. .00 0. .00 XXXX4002

ATOM 4003 CE1 TYR B 157 20. .458 52. .880 49. .106 1. .00 0. .00 XXXX4003

ATOM 4004 CE2 TYR B 157 20. .752 51. .410 47. .241 1. .00 0. .00 XXXX4004

ATOM 4005 CZ TYR B 157 20. .208 51. .678 48. .481 1. .00 0. .00 XXXX4005

ATOM 4006 OH TYR B 157 19. .413 50. .739 49. .098 1. .00 0. .00 XXXX4006

ATOM 4007 N VAL B 158 24. .256 55. .015 48. .969 1. .00 0. .00 XXXX4007

ATOM 4008 CA VAL B 158 24. .921 55. .121 50. .265 1. .00 0. .00 XXXX4008

ATOM 4009 C VAL B 158 24. .807 53. .879 51. .156 1. .00 0. .00 XXXX4009

ATOM 4010 O VAL B 158 25. .737 53. .575 51. .905 1. .00 0. .00 XXXX4010

ATOM 4011 CB VAL B 158 24. .397 56. .337 51. .056 1. .00 0. .00 XXXX4011

ATOM 4012 CGI VAL B 158 22. .928 56. .157 51. .412 1. .00 0. .00 XXXX4012

ATOM 4013 CG2 VAL B 158 25. .238 56. .553 52. .304 1. .00 0. .00 XXXX4013

ATOM 4014 N PHE B 159 23. .692 53. .155 51. .091 1. .00 0. .00 XXXX4014

ATOM 4015 CA PHE B 159 23. .550 51. .990 51. .964 1. .00 0. .00 XXXX4015

ATOM 4016 C PHE B 159 24. .546 50. .881 51. .624 1. .00 0. .00 XXXX4016

ATOM 4017 O PHE B 159 25. .331 50. .472 52. .478 1. .00 0. .00 XXXX4017

ATOM 4018 CB PHE B 159 22. .137 51. .409 51. .921 1. .00 0. .00 XXXX4018

ATOM 4019 CG PHE B 159 22. .065 50. .003 52. .452 1. .00 0. .00 XXXX4019

ATOM 4020 CD1 PHE B 159 22. .353 49. .741 53. .782 1. .00 0. .00 XXXX4020

ATOM 4021 CD2 PHE B 159 21. .749 48. .942 51. .620 1. .00 0. .00 XXXX4021

ATOM 4022 CE1 PHE B 159 22. .309 48. .451 54. .278 1. .00 0. .00 XXXX4022

ATOM 4023 CE2 PHE B 159 21. .701 47. .648 52. .111 1. .00 0. .00 XXXX4023

ATOM 4024 CZ PHE B 159 21. .982 47. .403 53. .440 1. .00 0. .00 XXXX4024

ATOM 4025 N PRO B 160 24. .515 50. .386 50. .376 1. .00 0. .00 XXXX4025

ATOM 4026 CA PRO B 160 25. .434 49. .309 49. .994 1. .00 0. .00 XXXX4026

ATOM 4027 C PRO B 160 26. .897 49. .726 50. .119 1. .00 0. .00 XXXX4027

ATOM 4028 O PRO B 160 27. .733 48. .907 50. .506 1. .00 0. .00 XXXX4028

ATOM 4029 CB PRO B 160 25. .059 49. .034 48. .536 1. .00 0. .00 XXXX4029

ATOM 4030 CG PRO B 160 23. .621 49. .438 48. .451 1. .00 0. .00 XXXX4030

ATOM 4031 CD PRO B 160 23. .532 50. .663 49. .314 1. .00 0. .00 XXXX4031

ATOM 4032 N ARG B 161 27. .193 50. .984 49. .810 1. .00 0. .00 XXXX4032

ATOM 4033 CA ARG B 161 28. .555 51. .495 49. .920 1. .00 0. .00 XXXX4033

ATOM 4034 C ARG B 161 29. .019 51. .489 51. .372 1. .00 0. .00 XXXX4034

ATOM 4035 O ARG B 161 30. .129 51. .056 51. .677 1. .00 0. .00 XXXX4035

ATOM 4036 CB ARG B 161 28. .650 52. .913 49. .351 1. .00 0. .00 XXXX4036

ATOM 4037 CG ARG B 161 28. .459 53. .011 47. .847 1. .00 0. .00 XXXX4037

ATOM 4038 CD ARG B 161 29. .758 52. .730 47. .114 1. .00 0. .00 XXXX4038

ATOM 4039 NE ARG B 161 29. .638 52. .953 45. .676 1. .00 0. .00 XXXX4039

ATOM 4040 CZ ARG B 161 30. .654 52. .875 44. .823 1. .00 0. .00 XXXX4040

ATOM 4041 NH1 ARG B 161 31. .870 52. .585 45. .264 1. .00 0. .00 XXXX4041

ATOM 4042 NH2 ARG B 161 30. .456 53. .092 43. .530 1. .00 0. .00 XXXX4042

ATOM 4043 N THR B 162 28. .154 51. .958 52. .267 1. .00 0. .00 XXXX4043

ATOM 4044 CA THR B 162 28. .470 52. .008 53. .690 1. .00 0. .00 XXXX4044

ATOM 4045 C THR B 162 28. .464 50. .617 54. .320 1. .00 0. .00 XXXX4045

ATOM 4046 O THR B 162 29. .307 50. .302 55. .163 1. .00 0. .00 XXXX4046

ATOM 4047 CB THR B 162 27. .481 52. .907 54. .450 1. .00 0. .00 XXXX4047

ATOM 4048 OG1 THR B 162 27. .466 54. .211 53. .857 1. .00 0. .00 XXXX4048

ATOM 4049 CG2 THR B 162 27. .881 53. .024 55. .913 1. .00 0. .00 XXXX4049

ATOM 4050 N ALA B 163 27. .504 49. .794 53. .909 1. .00 0. .00 XXXX4050

ATOM 4051 CA ALA B 163 27. .406 48. .422 54. .391 1. .00 0. .00 XXXX4051

ATOM 4052 C ALA B 163 28. .695 47. .658 54. .108 1. .00 0. .00 XXXX4052

ATOM 4053 O ALA B 163 29. .225 46. .973 54. .981 1. .00 0. .00 XXXX4053

ATOM 4054 CB ALA B 163 26. .216 47. .720 53. .752 1. .00 0. .00 XXXX4054

ATOM 4055 N ASN B 164 29. .202 47. .796 52. .888 1. .00 0. .00 XXXX4055

ATOM 4056 CA ASN B 164 30. .421 47. .110 52. .487 1. .00 0. .00 XXXX4056

ATOM 4057 C ASN B 164 31. .649 47. .680 53. .189 1. .00 0. .00 XXXX4057

ATOM 4058 O ASN B 164 32. .611 46. .958 53. .450 1. .00 0. .00 XXXX4058

ATOM 4059 CB ASN B 164 30. .594 47. .180 50. .970 1. .00 0. .00 XXXX4059

ATOM 4060 CG ASN B 164 29. .601 46. .300 50. .236 1. .00 0. .00 XXXX4060

ATOM 4061 OD1 ASN B 164 29. .076 45. .341 50. .802 1. .00 0. .00 XXXX4061

ATOM 4062 ND2 ASN B 164 29. .336 46. .621 48. .975 1. .00 0. .00 XXXX4062

ATOM 4063 N LYS B 165 31. .616 48. .975 53. .491 1. .00 0. .00 XXXX4063 Attorney Docket No. 35327-522001 WO

ATOM 4064 CA LYS B 165 32. .673 49. .586 54. .291 1. .00 0. .00 XXXX4064

ATOM 4065 C LYS B 165 32. .720 48. .943 55. .674 1. .00 0. .00 XXXX4065

ATOM 4066 O LYS B 165 33. .794 48. .665 56. .208 1. .00 0. .00 XXXX4066

ATOM 4067 CB LYS B 165 32. .463 51. .097 54. .417 1. .00 0. .00 XXXX4067

ATOM 4068 CG LYS B 165 33. .557 51. .799 55. .212 1. .00 0. .00 XXXX4068

ATOM 4069 CD LYS B 165 33. .268 53. .282 55. .392 1. .00 0. .00 XXXX4069

ATOM 4070 CE LYS B 165 34. .374 53. .963 56. .187 1. .00 0. .00 XXXX4070

ATOM 4071 NZ LYS B 165 34. .167 55. .434 56. .289 1. .00 0. .00 XXXX4071

ATOM 4072 N ILE B 166 31. .543 48. .708 56. .247 1. .00 0. .00 XXXX4072

ATOM 4073 CA ILE B 166 31. .435 48. .033 57. .534 1. .00 0. .00 XXXX4073

ATOM 4074 C ILE B 166 31. .884 46. .580 57. .428 1. .00 0. .00 XXXX4074

ATOM 4075 O ILE B 166 32. .649 46. .095 58. .261 1. .00 0. .00 XXXX4075

ATOM 4076 CB ILE B 166 29. .994 48. .071 58. .076 1. .00 0. .00 XXXX4076

ATOM 4077 CGI ILE B 166 29. .591 49. .505 58. .417 1. .00 0. .00 XXXX4077

ATOM 4078 CG2 ILE B 166 29. .865 47. .181 59. .302 1. .00 0. .00 XXXX4078

ATOM 4079 CD1 ILE B 166 28. .117 49. .664 58. .717 1. .00 0. .00 XXXX4079

ATOM 4080 N ILE B 167 31. .399 45. .895 56. .397 1. .00 0. .00 XXXX4080

ATOM 4081 CA ILE B 167 31. .709 44. .485 56. .187 1. .00 0. .00 XXXX4081

ATOM 4082 C ILE B 167 33. .210 44. .245 56. .044 1. .00 0. .00 XXXX4082

ATOM 4083 O ILE B 167 33. .747 43. .289 56. .604 1. .00 0. .00 XXXX4083

ATOM 4084 CB ILE B 167 30. .985 43. .934 54. .942 1. .00 0. .00 XXXX4084

ATOM 4085 CGI ILE B 167 29. .467 43. .971 55. .152 1. .00 0. .00 XXXX4085

ATOM 4086 CG2 ILE B 167 31. .445 42. .517 54. .637 1. .00 0. .00 XXXX4086

ATOM 4087 CD1 ILE B 167 28. .668 43. .553 53. .937 1. .00 0. .00 XXXX4087

ATOM 4088 N LYS B 168 33. .884 45. .109 55. .293 1. .00 0. .00 XXXX4088

ATOM 4089 CA LYS B 168 35. .324 44. .976 55. .096 1. .00 0. .00 XXXX4089

ATOM 4090 C LYS B 168 36. .098 45. .195 56. .393 1. .00 0. .00 XXXX4090

ATOM 4091 O LYS B 168 37. .098 44. .524 56. .644 1. .00 0. .00 XXXX4091

ATOM 4092 CB LYS B 168 35. .817 45. .945 54. .018 1. .00 0. .00 XXXX4092

ATOM 4093 CG LYS B 168 35. .422 45. .538 52. .605 1. .00 0. .00 XXXX4093

ATOM 4094 CD LYS B 168 36. .188 46. .326 51. .553 1. .00 0. .00 XXXX4094

ATOM 4095 CE LYS B 168 35. .510 47. .645 51. .236 1. .00 0. .00 XXXX4095

ATOM 4096 NZ LYS B 168 36. .093 48. .282 50. .020 1. .00 0. .00 XXXX4096

ATOM 4097 N ALA B 169 35. .641 46. .139 57. .210 1. .00 0. .00 XXXX4097

ATOM 4098 CA ALA B 169 36. .293 46. .421 58. .484 1. .00 0. .00 XXXX4098

ATOM 4099 C ALA B 169 36. .178 45. .224 59. .422 1. .00 0. .00 XXXX4099

ATOM 4100 O ALA B 169 37. .123 44. .884 60. .135 1. .00 0. .00 XXXX4100

ATOM 4101 CB ALA B 169 35. .695 47. .665 59. .127 1. .00 0. .00 XXXX4101

ATOM 4102 N TYR B 170 35. .010 44. .589 59. .415 1. .00 0. .00 XXXX4102

ATOM 4103 CA TYR B 170 34. .753 43. .434 60. .265 1. .00 0. .00 XXXX4103

ATOM 4104 C TYR B 170 35. .530 42. .209 59. .784 1. .00 0. .00 XXXX4104

ATOM 4105 O TYR B 170 36. .123 41. .487 60. .587 1. .00 0. .00 XXXX4105

ATOM 4106 CB TYR B 170 33. .255 43. .126 60. .305 1. .00 0. .00 XXXX4106

ATOM 4107 CG TYR B 170 32. .833 42. .253 61. .467 1. .00 0. .00 XXXX4107

ATOM 4108 CD1 TYR B 170 33. .690 42. .022 62. .538 1. .00 0. .00 XXXX4108

ATOM 4109 CD2 TYR B 170 31. .576 41. .662 61. .495 1. .00 0. .00 XXXX4109

ATOM 4110 CE1 TYR B 170 33. .304 41. .226 63. .605 1. .00 0. .00 XXXX4110

ATOM 4111 CE2 TYR B 170 31. .183 40. .864 62. .556 1. .00 0. .00 XXXX4111

ATOM 4112 CZ TYR B 170 32. .049 40. .649 63. .607 1. .00 0. .00 XXXX4112

ATOM 4113 OH TYR B 170 31. .655 39. .855 64. .661 1. .00 0. .00 XXXX4113

ATOM 4114 N LEU B 171 35. .521 41. .980 58. .473 1. .00 0. .00 XXXX4114

ATOM 4115 CA LEU B 171 36. .250 40. .859 57. .882 1. .00 0. .00 XXXX4115

ATOM 4116 C LEU B 171 37. .741 40. .943 58. .182 1. .00 0. .00 XXXX4116

ATOM 4117 O LEU B 171 38. .383 39. .929 58. .450 1. .00 0. .00 XXXX4117

ATOM 4118 CB LEU B 171 36. .023 40. .797 56. .370 1. .00 0. .00 XXXX4118

ATOM 4119 CG LEU B 171 34. .759 40. .069 55. .908 1. .00 0. .00 XXXX4119

ATOM 4120 CD1 LEU B 171 34. .625 40. .132 54. .393 1. .00 0. .00 XXXX4120

ATOM 4121 CD2 LEU B 171 34. .763 38. .624 56. .391 1. .00 0. .00 XXXX4121

ATOM 4122 N LYS B 172 38. .289 42. .153 58. .127 1. .00 0. .00 XXXX4122

ATOM 4123 CA LYS B 172 39. .687 42. .371 58. .478 1. .00 0. .00 XXXX4123

ATOM 4124 C LYS B 172 39. .929 41. .968 59. .927 1. .00 0. .00 XXXX4124

ATOM 4125 O LYS B 172 40. .953 41. .371 60. .258 1. .00 0. .00 XXXX4125

ATOM 4126 CB LYS B 172 40. .084 43. .833 58. .263 1. .00 0. .00 XXXX4126

ATOM 4127 CG LYS B 172 41. .493 44. .160 58. .737 1. .00 0. .00 XXXX4127

ATOM 4128 CD LYS B 172 41. .873 45. .598 58. .431 1. .00 0. .00 XXXX4128

ATOM 4129 CE LYS B 172 43. .324 45. .870 58. .798 1. .00 0. .00 XXXX4129

ATOM 4130 NZ LYS B 172 43. .721 47. .275 58. .509 1. .00 0. .00 XXXX4130 Attorney Docket No. 35327-522001 WO

ATOM 4131 N TYR B 173 38. .971 42. .304 60. .784 1. .00 0. .00 XXXX4131

ATOM 4132 CA TYR B 173 39. .046 41. .982 62. .202 1. .00 0. .00 XXXX4132

ATOM 4133 C TYR B 173 39. .011 40. .473 62. .435 1. .00 0. .00 XXXX4133

ATOM 4134 O TYR B 173 39. .720 39. .951 63. .296 1. .00 0. .00 XXXX4134

ATOM 4135 CB TYR B 173 37. .897 42. .662 62. .952 1. .00 0. .00 XXXX4135

ATOM 4136 CG TYR B 173 37. .827 42. .338 64. .426 1. .00 0. .00 XXXX4136

ATOM 4137 CD1 TYR B 173 38. .664 42. .968 65. .336 1. .00 0. .00 XXXX4137

ATOM 4138 CD2 TYR B 173 36. .913 41. .410 64. .910 1. .00 0. .00 XXXX4138

ATOM 4139 CE1 TYR B 173 38. .599 42. .680 66. .685 1. .00 0. .00 XXXX4139

ATOM 4140 CE2 TYR B 173 36. .841 41. .115 66. .257 1. .00 0. .00 XXXX4140

ATOM 4141 CZ TYR B 173 37. .687 41. .754 67. .140 1. .00 0. .00 XXXX4141

ATOM 4142 OH TYR B 173 37. .618 41. .464 68. .484 1. .00 0. .00 XXXX4142

ATOM 4143 N LEU B 174 38. .184 39. .779 61. .658 1. .00 0. .00 XXXX4143

ATOM 4144 CA LEU B 174 37. .970 38. .348 61. .846 1. .00 0. .00 XXXX4144

ATOM 4145 C LEU B 174 39. .070 37. .500 61. .215 1. .00 0. .00 XXXX4145

ATOM 4146 O LEU B 174 39. .397 36. .424 61. .715 1. .00 0. .00 XXXX4146

ATOM 4147 CB LEU B 174 36. .611 37. .939 61. .273 1. .00 0. .00 XXXX4147

ATOM 4148 CG LEU B 174 35. .380 38. .489 61. .998 1. .00 0. .00 XXXX4148

ATOM 4149 CD1 LEU B 174 34. .119 38. .243 61. .180 1. .00 0. .00 XXXX4149

ATOM 4150 CD2 LEU B 174 35. .251 37. .884 63. .390 1. .00 0. .00 XXXX4150

ATOM 4151 N GLY B 175 39. .639 37. .989 60. .118 1. .00 0. .00 XXXX4151

ATOM 4152 CA GLY B 175 40. .666 37. .253 59. .405 1. .00 0. .00 XXXX4152

ATOM 4153 C GLY B 175 40. .197 36. .748 58. .053 1. .00 0. .00 XXXX4153

ATOM 4154 O GLY B 175 40. .822 35. .873 57. .456 1. .00 0. .00 XXXX4154

ATOM 4155 N GLY B 176 39. .090 37. .304 57. .571 1. .00 0. .00 XXXX4155

ATOM 4156 CA GLY B 176 38. .590 36. .992 56. .244 1. .00 0. .00 XXXX4156

ATOM 4157 C GLY B 176 38. .999 38. .067 55. .258 1. .00 0. .00 XXXX4157

ATOM 4158 O GLY B 176 39. .588 39. .076 55. .646 1. .00 0. .00 XXXX4158

ATOM 4159 N VAL B 177 38. .694 37. .860 53. .981 1. .00 0. .00 XXXX4159

ATOM 4160 CA VAL B 177 39. .044 38. .844 52. .963 1. .00 0. .00 XXXX4160

ATOM 4161 C VAL B 177 37. .922 39. .055 51. .955 1. .00 0. .00 XXXX4161

ATOM 4162 O VAL B 177 37. .036 38. .212 51. .802 1. .00 0. .00 XXXX4162

ATOM 4163 CB VAL B 177 40. .313 38. .435 52. .194 1. .00 0. .00 XXXX4163

ATOM 4164 CGI VAL B 177 41. .526 38. .450 53. .116 1. .00 0. .00 XXXX4164

ATOM 4165 CG2 VAL B 177 40. .129 37. .064 51. .565 1. .00 0. .00 XXXX4165

ATOM 4166 N VAL B 178 37. .969 40. .193 51. .273 1. .00 0. .00 XXXX4166

ATOM 4167 CA VAL B 178 37. .061 40. .469 50. .171 1. .00 0. .00 XXXX4167

ATOM 4168 C VAL B 178 37. .818 40. .233 48. .873 1. .00 0. .00 XXXX4168

ATOM 4169 O VAL B 178 38. .887 40. .805 48. .659 1. .00 0. .00 XXXX4169

ATOM 4170 CB VAL B 178 36. .523 41. .908 50. .218 1. .00 0. .00 XXXX4170

ATOM 4171 CGI VAL B 178 35. .739 42. .223 48. .953 1. .00 0. .00 XXXX4171

ATOM 4172 CG2 VAL B 178 35. .657 42. .108 51. .453 1. .00 0. .00 XXXX4172

ATOM 4173 N VAL B 179 37. .267 39. .388 48. .009 1. .00 0. .00 XXXX4173

ATOM 4174 CA VAL B 179 37. .940 39. .029 46. .765 1. .00 0. .00 XXXX4174

ATOM 4175 C VAL B 179 37. .249 39. .658 45. .563 1. .00 0. .00 XXXX4175

ATOM 4176 O VAL B 179 37. .622 39. .406 44. .417 1. .00 0. .00 XXXX4176

ATOM 4177 CB VAL B 179 38. .002 37. .501 46. .577 1. .00 0. .00 XXXX4177

ATOM 4178 CGI VAL B 179 38. .879 36. .870 47. .653 1. .00 0. .00 XXXX4178

ATOM 4179 CG2 VAL B 179 36. .602 36. .901 46. .589 1. .00 0. .00 XXXX4179

ATOM 4180 N GLY B 180 36. .240 40. .478 45. .833 1. .00 0. .00 XXXX4180

ATOM 4181 CA GLY B 180 35. .530 41. .183 44. .785 1. .00 0. .00 XXXX4181

ATOM 4182 C GLY B 180 34. .512 42. .157 45. .344 1. .00 0. .00 XXXX4182

ATOM 4183 O GLY B 180 33. .933 41. .930 46. .406 1. .00 0. .00 XXXX4183

ATOM 4184 N GLU B 181 34. .293 43. .247 44. .619 1. .00 0. .00 XXXX4184

ATOM 4185 CA GLU B 181 33. .359 44. .280 45. .045 1. .00 0. .00 XXXX4185

ATOM 4186 C GLU B 181 32. .831 45. .034 43. .834 1. .00 0. .00 XXXX4186

ATOM 4187 O GLU B 181 33. .591 45. .687 43. .121 1. .00 0. .00 XXXX4187

ATOM 4188 CB GLU B 181 34. .028 45. .250 46. .023 1. .00 0. .00 XXXX4188

ATOM 4189 CG GLU B 181 33. .125 46. .386 46. .478 1. .00 0. .00 XXXX4189

ATOM 4190 CD GLU B 181 33. .815 47. .335 47. .438 1. .00 0. .00 XXXX4190

ATOM 4191 OE1 GLU B 181 33. .141 48. .247 47. .961 1. .00 0. .00 XXXX4191

ATOM 4192 OE2 GLU B 181 35. .030 47. .167 47. .672 1. .00 0. .00 XXXX4192

ATOM 4193 N GLU B 182 31. .526 44. .946 43. .606 1. .00 0. .00 XXXX4193

ATOM 4194 CA GLU B 182 30. .923 45. .577 42. .440 1. .00 0. .00 XXXX4194

ATOM 4195 C GLU B 182 29. .607 46. .254 42. .789 1. .00 0. .00 XXXX4195

ATOM 4196 O GLU B 182 28. .845 45. .763 43. .623 1. .00 0. .00 XXXX4196

ATOM 4197 CB GLU B 182 30. .700 44. .548 41. .330 1. .00 0. .00 XXXX4197 Attorney Docket No. 35327-522001 WO

ATOM 4198 CG GLU B 182 31. .974 43. .906 40. .812 1. .00 0. .00 XXXX4198

ATOM 4199 CD GLU B 182 32. .809 44. .864 39. .989 1. .00 0. .00 XXXX4199

ATOM 4200 OE1 GLU B 182 32. .219 45. .703 39. .275 1. .00 0. .00 XXXX4200

ATOM 4201 OE2 GLU B 182 34. .053 44. .780 40. .057 1. .00 0. .00 XXXX4201

ATOM 4202 N TYR B 183 29. .348 47. .387 42. .145 1. .00 0. .00 XXXX4202

ATOM 4203 CA TYR B 183 28. .094 48. .105 42. .324 1. .00 0. .00 XXXX4203

ATOM 4204 C TYR B 183 27. .397 48. .323 40. .987 1. .00 0. .00 XXXX4204

ATOM 4205 O TYR B 183 28. .043 48. .579 39. .971 1. .00 0. .00 XXXX4205

ATOM 4206 CB TYR B 183 28. .340 49. .447 43. .018 1. .00 0. .00 XXXX4206

ATOM 4207 CG TYR B 183 28. .980 49. .309 44. .380 1. .00 0. .00 XXXX4207

ATOM 4208 CD1 TYR B 183 28. .204 49. .151 45. .521 1. .00 0. .00 XXXX4208

ATOM 4209 CD2 TYR B 183 30. .361 49. .325 44. .524 1. .00 0. .00 XXXX4209

ATOM 4210 CE1 TYR B 183 28. .787 49. .022 46. .769 1. .00 0. .00 XXXX4210

ATOM 4211 CE2 TYR B 183 30. .952 49. .196 45. .765 1. .00 0. .00 XXXX4211

ATOM 4212 CZ TYR B 183 30. .161 49. .044 46. .884 1. .00 0. .00 XXXX4212

ATOM 4213 OH TYR B 183 30. .748 48. .913 48. .122 1. .00 0. .00 XXXX4213

ATOM 4214 N THR B 184 26. .074 48. .217 40. .994 1. .00 0. .00 XXXX4214

ATOM 4215 CA THR B 184 25. .274 48. .536 39. .822 1. .00 0. .00 XXXX4215

ATOM 4216 C THR B 184 24. .246 49. .595 40. .193 1. .00 0. .00 XXXX4216

ATOM 4217 O THR B 184 23. .752 49. .610 41. .320 1. .00 0. .00 XXXX4217

ATOM 4218 CB THR B 184 24. .558 47. .293 39. .258 1. .00 0. .00 XXXX4218

ATOM 4219 OG1 THR B 184 23. .735 46. .711 40. .276 1. .00 0. .00 XXXX4219

ATOM 4220 CG2 THR B 184 25. .570 46. .263 38. .776 1. .00 0. .00 XXXX4220

ATOM 4221 N PRO B 185 23. .932 50. .495 39. .251 1. .00 0. .00 XXXX4221

ATOM 4222 CA PRO B 185 22. .896 51. .504 39. .491 1. .00 0. .00 XXXX4222

ATOM 4223 C PRO B 185 21. .576 50. .852 39. .886 1. .00 0. .00 XXXX4223

ATOM 4224 O PRO B 185 21. .277 49. .757 39. .405 1. .00 0. .00 XXXX4224

ATOM 4225 CB PRO B 185 22. .775 52. .214 38. .139 1. .00 0. .00 XXXX4225

ATOM 4226 CG PRO B 185 24. .098 51. .997 37. .481 1. .00 0. .00 XXXX4226

ATOM 4227 CD PRO B 185 24. .535 50. .628 37. .913 1. .00 0. .00 XXXX4227

ATOM 4228 N LEU B 186 20. .818 51. .495 40. .768 1. .00 0. .00 XXXX4228

ATOM 4229 CA LEU B 186 19. .474 51. .033 41. .087 1. .00 0. .00 XXXX4229

ATOM 4230 C LEU B 186 18. .684 50. .850 39. .797 1. .00 0. .00 XXXX4230

ATOM 4231 O LEU B 186 18. .676 51. .734 38. .941 1. .00 0. .00 XXXX4231

ATOM 4232 CB LEU B 186 18. .768 52. .024 42. .016 1. .00 0. .00 XXXX4232

ATOM 4233 CG LEU B 186 19. .090 51. .920 43. .510 1. .00 0. .00 XXXX4233

ATOM 4234 CD1 LEU B 186 18. .592 53. .146 44. .253 1. .00 0. .00 XXXX4234

ATOM 4235 CD2 LEU B 186 18. .486 50. .657 44. .105 1. .00 0. .00 XXXX4235

ATOM 4236 N GLY B 187 18. .024 49. .704 39. .660 1. .00 0. .00 XXXX4236

ATOM 4237 CA GLY B 187 17. .217 49. .425 38. .485 1. .00 0. .00 XXXX4237

ATOM 4238 C GLY B 187 17. .966 48. .713 37. .371 1. .00 0. .00 XXXX4238

ATOM 4239 O GLY B 187 17. .370 48. .331 36. .364 1. .00 0. .00 XXXX4239

ATOM 4240 N HIS B 188 19. .275 48. .552 37. .544 1. .00 0. .00 XXXX4240

ATOM 4241 CA HIS B 188 20. .108 47. .807 36. .600 1. .00 0. .00 XXXX4241

ATOM 4242 C HIS B 188 19. .570 46. .390 36. .390 1. .00 0. .00 XXXX4242

ATOM 4243 O HIS B 188 19. .054 45. .778 37. .324 1. .00 0. .00 XXXX4243

ATOM 4244 CB HIS B 188 21. .553 47. .758 37. .103 1. .00 0. .00 XXXX4244

ATOM 4245 CG HIS B 188 22. .556 47. .412 36. .046 1. .00 0. .00 XXXX4245

ATOM 4246 ND1 HIS B 188 23. .013 48. .331 35. .126 1. .00 0. .00 XXXX4246

ATOM 4247 CD2 HIS B 188 23. .195 46. .251 35. .768 1. .00 0. .00 XXXX4247

ATOM 4248 CE1 HIS B 188 23. .889 47. .750 34. .325 1. .00 0. .00 XXXX4248

ATOM 4249 NE2 HIS B 188 24. .017 46. .488 34. .693 1. .00 0. .00 XXXX4249

ATOM 4250 N THR B 189 19. .684 45. .868 35. .170 1. .00 0. .00 XXXX4250

ATOM 4251 CA THR B 189 19. .148 44. .539 34. .875 1. .00 0. .00 XXXX4251

ATOM 4252 C THR B 189 20. .137 43. .593 34. .187 1. .00 0. .00 XXXX4252

ATOM 4253 O THR B 189 19. .871 42. .397 34. .075 1. .00 0. .00 XXXX4253

ATOM 4254 CB THR B 189 17. .885 44. .632 33. .993 1. .00 0. .00 XXXX4254

ATOM 4255 OG1 THR B 189 18. .220 45. .219 32. .730 1. .00 0. .00 XXXX4255

ATOM 4256 CG2 THR B 189 16. .817 45. .472 34. .676 1. .00 0. .00 XXXX4256

ATOM 4257 N ASP B 190 21. .267 44. .118 33. .723 1. .00 0. .00 XXXX4257

ATOM 4258 CA ASP B 190 22. .258 43. .288 33. .036 1. .00 0. .00 XXXX4258

ATOM 4259 C ASP B 190 23. .388 42. .885 33. .983 1. .00 0. .00 XXXX4259

ATOM 4260 O ASP B 190 24. .288 43. .678 34. .264 1. .00 0. .00 XXXX4260

ATOM 4261 CB ASP B 190 22. .827 44. .026 31. .820 1. .00 0. .00 XXXX4261

ATOM 4262 CG ASP B 190 23. .676 43. .129 30. .930 1. .00 0. .00 XXXX4262

ATOM 4263 OD1 ASP B 190 23. .901 41. .954 31. .294 1. .00 0. .00 XXXX4263

ATOM 4264 OD2 ASP B 190 24. .129 43. .605 29. .867 1. .00 0. .00 XXXX4264 Attorney Docket No. 35327-522001 WO

ATOM 4265 N TYR B 191 23. .337 41. .648 34. .472 1. .00 0. .00 XXXX4265

ATOM 4266 CA TYR B 191 24. .323 41. .170 35. .437 1. .00 0. .00 XXXX4266

ATOM 4267 C TYR B 191 25. .256 40. .090 34. .890 1. .00 0. .00 XXXX4267

ATOM 4268 O TYR B 191 25. .925 39. .396 35. .655 1. .00 0. .00 XXXX4268

ATOM 4269 CB TYR B 191 23. .608 40. .669 36. .693 1. .00 0. .00 XXXX4269

ATOM 4270 CG TYR B 191 23. .078 41. .814 37. .519 1. .00 0. .00 XXXX4270

ATOM 4271 CD1 TYR B 191 23. .873 42. .426 38. .478 1. .00 0. .00 XXXX4271

ATOM 4272 CD2 TYR B 191 21. .799 42. .312 37. .310 1. .00 0. .00 XXXX4272

ATOM 4273 CE1 TYR B 191 23. .403 43. .488 39. .222 1. .00 0. .00 XXXX4273

ATOM 4274 CE2 TYR B 191 21. .318 43. .373 38. .049 1. .00 0. .00 XXXX4274

ATOM 4275 CZ TYR B 191 22. .125 43. .957 39. .004 1. .00 0. .00 XXXX4275

ATOM 4276 OH TYR B 191 21. .656 45. .015 39. .743 1. .00 0. .00 XXXX4276

ATOM 4277 N SER B 192 25. .299 39. .949 33. .569 1. .00 0. .00 XXXX4277

ATOM 4278 CA SER B 192 26. .187 38. .979 32. .938 1. .00 0. .00 XXXX4278

ATOM 4279 C SER B 192 27. .649 39. .292 33. .257 1. .00 0. .00 XXXX4279

ATOM 4280 O SER B 192 28. .447 38. .391 33. .520 1. .00 0. .00 XXXX4280

ATOM 4281 CB SER B 192 25. .973 38. .959 31. .427 1. .00 0. .00 XXXX4281

ATOM 4282 OG SER B 192 26. .260 40. .228 30. .874 1. .00 0. .00 XXXX4282

ATOM 4283 N SER B 193 27. .991 40. .576 33. .228 1. .00 0. .00 XXXX4283

ATOM 4284 CA SER B 193 29. .356 41. .017 33. .497 1. .00 0. .00 XXXX4284

ATOM 4285 C SER B 193 29. .766 40. .717 34. .937 1. .00 0. .00 XXXX4285

ATOM 4286 O SER B 193 30. .832 40. .152 35. .181 1. .00 0. .00 XXXX4286

ATOM 4287 CB SER B 193 29. .498 42. .511 33. .211 1. .00 0. .00 XXXX4287

ATOM 4288 OG SER B 193 30. .733 43. .007 33. .699 1. .00 0. .00 XXXX4288

ATOM 4289 N VAL B 194 28. .916 41. .102 35. .886 1. .00 0. .00 XXXX4289

ATOM 4290 CA VAL B 194 29. .146 40. .798 37. .295 1. .00 0. .00 XXXX4290

ATOM 4291 C VAL B 194 29. .256 39. .294 37. .530 1. .00 0. .00 XXXX4291

ATOM 4292 O VAL B 194 30. .157 38. .829 38. .227 1. .00 0. .00 XXXX4292

ATOM 4293 CB VAL B 194 28. .024 41. .361 38. .188 1. .00 0. .00 XXXX4293

ATOM 4294 CGI VAL B 194 28. .072 40. .719 39. .569 1. .00 0. .00 XXXX4294

ATOM 4295 CG2 VAL B 194 28. .128 42. .875 38. .284 1. .00 0. .00 XXXX4295

ATOM 4296 N ILE B 195 28. .329 38. .540 36. .948 1. .00 0. .00 XXXX4296

ATOM 4297 CA ILE B 195 28. .296 37. .092 37. .128 1. .00 0. .00 XXXX4297

ATOM 4298 C ILE B 195 29. .533 36. .416 36. .535 1. .00 0. .00 XXXX4298

ATOM 4299 O ILE B 195 30. .054 35. .455 37. .103 1. .00 0. .00 XXXX4299

ATOM 4300 CB ILE B 195 27. .025 36. .483 36. .505 1. .00 0. .00 XXXX4300

ATOM 4301 CGI ILE B 195 25. .798 36. .864 37. .339 1. .00 0. .00 XXXX4301

ATOM 4302 CD1 ILE B 195 24. .475 36. .586 36. .653 1. .00 0. .00 XXXX4302

ATOM 4303 CG2 ILE B 195 27. .149 34. .972 36. .415 1. .00 0. .00 XXXX4303

ATOM 4304 N ASN B 196 29. .999 36. .915 35. .396 1. .00 0. .00 XXXX4304

ATOM 4305 CA ASN B 196 31. .238 36. .412 34. .811 1. .00 0. .00 XXXX4305

ATOM 4306 C ASN B 196 32. .431 36. .666 35. .727 1. .00 0. .00 XXXX4306

ATOM 4307 O ASN B 196 33. .326 35. .828 35. .837 1. .00 0. .00 XXXX4307

ATOM 4308 CB ASN B 196 31. .486 37. .038 33. .438 1. .00 0. .00 XXXX4308

ATOM 4309 CG ASN B 196 30. .661 36. .389 32. .345 1. .00 0. .00 XXXX4309

ATOM 4310 OD1 ASN B 196 30. .192 35. .260 32. .492 1. .00 0. .00 XXXX4310

ATOM 4311 ND2 ASN B 196 30. .488 37. .097 31. .236 1. .00 0. .00 XXXX4311

ATOM 4312 N LYS B 197 32. .444 37. .827 36. .377 1. .00 0. .00 XXXX4312

ATOM 4313 CA LYS B 197 33. .498 38. .153 37. .334 1. .00 0. .00 XXXX4313

ATOM 4314 C LYS B 197 33. .442 37. .235 38. .550 1. .00 0. .00 XXXX4314

ATOM 4315 O LYS B 197 34. .472 36. .774 39. .040 1. .00 0. .00 XXXX4315

ATOM 4316 CB LYS B 197 33. .396 39. .612 37. .787 1. .00 0. .00 XXXX4316

ATOM 4317 CG LYS B 197 33. .749 40. .632 36. .720 1. .00 0. .00 XXXX4317

ATOM 4318 CD LYS B 197 33. .550 42. .049 37. .235 1. .00 0. .00 XXXX4318

ATOM 4319 CE LYS B 197 33. .860 43. .078 36. .161 1. .00 0. .00 XXXX4319

ATOM 4320 NZ LYS B 197 33. .538 44. .458 36. .617 1. .00 0. .00 XXXX4320

ATOM 4321 N ILE B 198 32. .233 36. .980 39. .037 1. .00 0. .00 XXXX4321

ATOM 4322 CA ILE B 198 32. .040 36. .074 40. .161 1. .00 0. .00 XXXX4322

ATOM 4323 C ILE B 198 32. .532 34. .667 39. .821 1. .00 0. .00 XXXX4323

ATOM 4324 O ILE B 198 33. .192 34. .020 40. .635 1. .00 0. .00 XXXX4324

ATOM 4325 CB ILE B 198 30. .565 36. .017 40. .594 1. .00 0. .00 XXXX4325

ATOM 4326 CGI ILE B 198 30. .151 37. .346 41. .234 1. .00 0. .00 XXXX4326

ATOM 4327 CG2 ILE B 198 30. .345 34. .875 41. .569 1. .00 0. .00 XXXX4327

ATOM 4328 CD1 ILE B 198 28. .688 37. .410 41. .627 1. .00 0. .00 XXXX4328

ATOM 4329 N LYS B 199 32. .199 34. .198 38. .621 1. .00 0. .00 XXXX4329

ATOM 4330 CA LYS B 199 32. .661 32. .895 38. .153 1. .00 0. .00 XXXX4330

ATOM 4331 C LYS B 199 34. .184 32. .792 38. .156 1. .00 0. .00 XXXX4331 Attorney Docket No. 35327-522001 WO

ATOM 4332 O LYS B 199 34. .741 31. .742 38. .476 1. .00 0. .00 XXXX4332

ATOM 4333 CB LYS B 199 32. .131 32. .604 36. .745 1. .00 0. .00 XXXX4333

ATOM 4334 CG LYS B 199 30. .676 32. .169 36. .697 1. .00 0. .00 XXXX4334

ATOM 4335 CD LYS B 199 30. .263 31. .796 35. .281 1. .00 0. .00 XXXX4335

ATOM 4336 CE LYS B 199 28. .826 31. .308 35. .235 1. .00 0. .00 XXXX4336

ATOM 4337 NZ LYS B 199 28. .444 30. .838 33. .877 1. .00 0. .00 XXXX4337

ATOM 4338 N ALA B 200 34. .854 33. .883 37. .796 1. .00 0. .00 XXXX4338

ATOM 4339 CA ALA B 200 36. .311 33. .891 37. .726 1. .00 0. .00 XXXX4339

ATOM 4340 C ALA B 200 36. .950 34. .003 39. .108 1. .00 0. .00 XXXX4340

ATOM 4341 O ALA B 200 37. .987 33. .395 39. .371 1. .00 0. .00 XXXX4341

ATOM 4342 CB ALA B 200 36. .788 35. .028 36. .832 1. .00 0. .00 XXXX4342

ATOM 4343 N ALA B 201 36. .324 34. .773 39. .991 1. .00 0. .00 XXXX4343

ATOM 4344 CA ALA B 201 36. .886 35. .023 41. .314 1. .00 0. .00 XXXX4344

ATOM 4345 C ALA B 201 36. .693 33. .825 42. .239 1. .00 0. .00 XXXX4345

ATOM 4346 O ALA B 201 37. .501 33. .592 43. .137 1. .00 0. .00 XXXX4346

ATOM 4347 CB ALA B 201 36. .264 36. .271 41. .926 1. .00 0. .00 XXXX4347

ATOM 4348 N LYS B 202 35. .626 33. .066 42. .004 1. .00 0. .00 XXXX4348

ATOM 4349 CA LYS B 202 35. .302 31. .893 42. .814 1. .00 0. .00 XXXX4349

ATOM 4350 C LYS B 202 35. .297 32. .177 44. .317 1. .00 0. .00 XXXX4350

ATOM 4351 O LYS B 202 36. .047 31. .558 45. .071 1. .00 0. .00 XXXX4351

ATOM 4352 CB LYS B 202 36. .280 30. .757 42. .508 1. .00 0. .00 XXXX4352

ATOM 4353 CG LYS B 202 36. .200 30. .240 41. .080 1. .00 0. .00 XXXX4353

ATOM 4354 CD LYS B 202 37. .193 29. .114 40. .846 1. .00 0. .00 XXXX4354

ATOM 4355 CE LYS B 202 37. .003 28. .481 39. .477 1. .00 0. .00 XXXX4355

ATOM 4356 NZ LYS B 202 37. .115 29. .479 38. .379 1. .00 0. .00 XXXX4356

ATOM 4357 N PRO B 203 34. .447 33. .116 44. .758 1. .00 0. .00 XXXX4357

ATOM 4358 CA PRO B 203 34. .336 33. .447 46. .182 1. .00 0. .00 XXXX4358

ATOM 4359 C PRO B 203 33. .670 32. .333 46. .990 1. .00 0. .00 XXXX4359

ATOM 4360 O PRO B 203 33. .055 31. .441 46. .407 1. .00 0. .00 XXXX4360

ATOM 4361 CB PRO B 203 33. .470 34. .707 46. .174 1. .00 0. .00 XXXX4361

ATOM 4362 CG PRO B 203 32. .611 34. .542 44. .963 1. .00 0. .00 XXXX4362

ATOM 4363 CD PRO B 203 33. .508 33. .900 43. .936 1. .00 0. .00 XXXX4363

ATOM 4364 N ASP B 204 33. .792 32. .389 48. .313 1. .00 0. .00 XXXX4364

ATOM 4365 CA ASP B 204 33. .114 31. .433 49. .184 1. .00 0. .00 XXXX4365

ATOM 4366 C ASP B 204 31. .644 31. .793 49. .317 1. .00 0. .00 XXXX4366

ATOM 4367 O ASP B 204 30. .788 30. .925 49. .490 1. .00 0. .00 XXXX4367

ATOM 4368 CB ASP B 204 33. .764 31. .397 50. .569 1. .00 0. .00 XXXX4368

ATOM 4369 CG ASP B 204 35. .220 30. .992 50. .522 1. .00 0. .00 XXXX4369

ATOM 4370 OD1 ASP B 204 35. .634 30. .371 49. .520 1. .00 0. .00 XXXX4370

ATOM 4371 OD2 ASP B 204 35. .949 31. .292 51. .491 1. .00 0. .00 XXXX4371

ATOM 4372 N VAL B 205 31. .362 33. .088 49. .236 1. .00 0. .00 XXXX4372

ATOM 4373 CA VAL B 205 30. .018 33. .598 49. .449 1. .00 0. .00 XXXX4373

ATOM 4374 C VAL B 205 29. .843 34. .950 48. .774 1. .00 0. .00 XXXX4374

ATOM 4375 O VAL B 205 30. .779 35. .749 48. .702 1. .00 0. .00 XXXX4375

ATOM 4376 CB VAL B 205 29. .700 33. .739 50. .953 1. .00 0. .00 XXXX4376

ATOM 4377 CGI VAL B 205 30. .623 34. .763 51. .598 1. .00 0. .00 XXXX4377

ATOM 4378 CG2 VAL B 205 28. .241 34. .122 51. .161 1. .00 0. .00 XXXX4378

ATOM 4379 N VAL B 206 28. .640 35. .199 48. .273 1. .00 0. .00 XXXX4379

ATOM 4380 CA VAL B 206 28. .288 36. .520 47. .784 1. .00 0. .00 XXXX4380

ATOM 4381 C VAL B 206 27. .447 37. .233 48. .832 1. .00 0. .00 XXXX4381

ATOM 4382 O VAL B 206 26. .423 36. .712 49. .274 1. .00 0. .00 XXXX4382

ATOM 4383 CB VAL B 206 27. .511 36. .451 46. .456 1. .00 0. .00 XXXX4383

ATOM 4384 CGI VAL B 206 27. .139 37. .851 45. .988 1. .00 0. .00 XXXX4384

ATOM 4385 CG2 VAL B 206 28. .331 35. .728 45. .398 1. .00 0. .00 XXXX4385

ATOM 4386 N PHE B 207 27. .882 38. .420 49. .239 1. .00 0. .00 XXXX4386

ATOM 4387 CA PHE B 207 27. .082 39. .226 50. .149 1. .00 0. .00 XXXX4387

ATOM 4388 C PHE B 207 26. .330 40. .270 49. .343 1. .00 0. .00 XXXX4388

ATOM 4389 O PHE B 207 26. .919 41. .220 48. .828 1. .00 0. .00 XXXX4389

ATOM 4390 CB PHE B 207 27. .944 39. .884 51. .226 1. .00 0. .00 XXXX4390

ATOM 4391 CG PHE B 207 27. .180 40. .243 52. .470 1. .00 0. .00 XXXX4391

ATOM 4392 CD1 PHE B 207 26. .283 41. .299 52. .470 1. .00 0. .00 XXXX4392

ATOM 4393 CD2 PHE B 207 27. .343 39. .510 53. .634 1. .00 0. .00 XXXX4393

ATOM 4394 CE1 PHE B 207 25. .571 41. .624 53. .611 1. .00 0. .00 XXXX4394

ATOM 4395 CE2 PHE B 207 26. .634 39. .830 54. .778 1. .00 0. .00 XXXX4395

ATOM 4396 CZ PHE B 207 25. .748 40. .889 54. .767 1. .00 0. .00 XXXX4396

ATOM 4397 N ASN B 208 25. .019 40. .076 49. .242 1. .00 0. .00 XXXX4397

ATOM 4398 CA ASN B 208 24. .173 40. .856 48. .347 1. .00 0. .00 XXXX4398 Attorney Docket No. 35327-522001 WO

ATOM 4399 C ASN B 208 23. .475 42. .031 49. .022 1. .00 0. .00 XXXX4399

ATOM 4400 O ASN B 208 22. .643 41. .844 49. .911 1. .00 0. .00 XXXX4400

ATOM 4401 CB ASN B 208 23. .126 39. .940 47. .709 1. .00 0. .00 XXXX4401

ATOM 4402 CG ASN B 208 22. .131 40. .699 46. .857 1. .00 0. .00 XXXX4402

ATOM 4403 OD1 ASN B 208 22. .478 41. .685 46. .210 1. .00 0. .00 XXXX4403

ATOM 4404 ND2 ASN B 208 20. .881 40. .246 46. .859 1. .00 0. .00 XXXX4404

ATOM 4405 N THR B 209 23. .813 43. .241 48. .590 1. .00 0. .00 XXXX4405

ATOM 4406 CA THR B 209 23. .137 44. .438 49. .076 1. .00 0. .00 XXXX4406

ATOM 4407 C THR B 209 22. .377 45. .137 47. .952 1. .00 0. .00 XXXX4407

ATOM 4408 O THR B 209 22. .073 46. .326 48. .047 1. .00 0. .00 XXXX4408

ATOM 4409 CB THR B 209 24. .126 45. .436 49. .717 1. .00 0. .00 XXXX4409

ATOM 4410 OG1 THR B 209 25. .236 45. .658 48. .838 1. .00 0. .00 XXXX4410

ATOM 4411 CG2 THR B 209 24. .634 44. .901 51. .047 1. .00 0. .00 XXXX4411

ATOM 4412 N LEU B 210 22. .068 44. .393 46. .892 1. .00 0. .00 XXXX4412

ATOM 4413 CA LEU B 210 21. .184 44. .897 45. .845 1. .00 0. .00 XXXX4413

ATOM 4414 C LEU B 210 19. .832 45. .273 46. .438 1. .00 0. .00 XXXX4414

ATOM 4415 O LEU B 210 19. .294 44. .551 47. .277 1. .00 0. .00 XXXX4415

ATOM 4416 CB LEU B 210 20. .991 43. .857 44. .737 1. .00 0. .00 XXXX4416

ATOM 4417 CG LEU B 210 22. .181 43. .459 43. .859 1. .00 0. .00 XXXX4417

ATOM 4418 CD1 LEU B 210 21. .787 42. .322 42. .930 1. .00 0. .00 XXXX4418

ATOM 4419 CD2 LEU B 210 22. .700 44. .643 43. .059 1. .00 0. .00 XXXX4419

ATOM 4420 N ASN B 211 19. .290 46. .405 46. .000 1. .00 0. .00 XXXX4420

ATOM 4421 CA ASN B 211 17. .962 46. .832 46. .423 1. .00 0. .00 XXXX4421

ATOM 4422 C ASN B 211 17. .025 46. .987 45. .228 1. .00 0. .00 XXXX4422

ATOM 4423 O ASN B 211 17. .451 47. .373 44. .139 1. .00 0. .00 XXXX4423

ATOM 4424 CB ASN B 211 18. .043 48. .142 47. .209 1. .00 0. .00 XXXX4424

ATOM 4425 CG ASN B 211 18. .406 47. .925 48. .668 1. .00 0. .00 XXXX4425

ATOM 4426 OD1 ASN B 211 17. .581 48. .116 49. .562 1. .00 0. .00 XXXX4426

ATOM 4427 ND2 ASN B 211 19. .650 47. .528 48. .916 1. .00 0. .00 XXXX4427

ATOM 4428 N GLY B 212 15. .747 46. .683 45. .435 1. .00 0. .00 XXXX4428

ATOM 4429 CA GLY B 212 14. .751 46. .856 44. .393 1. .00 0. .00 XXXX4429

ATOM 4430 C GLY B 212 14. .765 45. .718 43. .390 1. .00 0. .00 XXXX4430

ATOM 4431 O GLY B 212 15. .342 44. .663 43. .649 1. .00 0. .00 XXXX4431

ATOM 4432 N ASP B 213 14. .135 45. .932 42. .237 1. .00 0. .00 XXXX4432

ATOM 4433 CA ASP B 213 13. .898 44. .846 41. .292 1. .00 0. .00 XXXX4433

ATOM 4434 C ASP B 213 15. .135 44. .468 40. .477 1. .00 0. .00 XXXX4434

ATOM 4435 O ASP B 213 15. .062 43. .616 39. .593 1. .00 0. .00 XXXX4435

ATOM 4436 CB ASP B 213 12. .735 45. .198 40. .355 1. .00 0. .00 XXXX4436

ATOM 4437 CG ASP B 213 12. .947 46. .503 39. .606 1. .00 0. .00 XXXX4437

ATOM 4438 OD1 ASP B 213 14. .110 46. .902 39. .381 1. .00 0. .00 XXXX4438

ATOM 4439 OD2 ASP B 213 11. .934 47. .131 39. .236 1. .00 0. .00 XXXX4439

ATOM 4440 N SER B 214 16. .263 45. .110 40. .767 1. .00 0. .00 XXXX4440

ATOM 4441 CA SER B 214 17. .548 44. .630 40. .276 1. .00 0. .00 XXXX4441

ATOM 4442 C SER B 214 17. .756 43. .183 40. .719 1. .00 0. .00 XXXX4442

ATOM 4443 O SER B 214 18. .384 42. .393 40. .018 1. .00 0. .00 XXXX4443

ATOM 4444 CB SER B 214 18. .694 45. .512 40. .777 1. .00 0. .00 XXXX4444

ATOM 4445 OG SER B 214 18. .853 46. .661 39. .963 1. .00 0. .00 XXXX4445

ATOM 4446 N ASN B 215 17. .221 42. .849 41. .891 1. .00 0. .00 XXXX4446

ATOM 4447 CA ASN B 215 17. .325 41. .500 42. .438 1. .00 0. .00 XXXX4447

ATOM 4448 C ASN B 215 16. .641 40. .455 41. .565 1. .00 0. .00 XXXX4448

ATOM 4449 O ASN B 215 17. .068 39. .301 41. .513 1. .00 0. .00 XXXX4449

ATOM 4450 CB ASN B 215 16. .737 41. .454 43. .848 1. .00 0. .00 XXXX4450

ATOM 4451 CG ASN B 215 17. .669 42. .046 44. .886 1. .00 0. .00 XXXX4451

ATOM 4452 OD1 ASN B 215 18. .631 41. .404 45. .307 1. .00 0. .00 XXXX4452

ATOM 4453 ND2 ASN B 215 17. .389 43. .275 45. .304 1. .00 0. .00 XXXX4453

ATOM 4454 N VAL B 216 15. .571 40. .860 40. .889 1. .00 0. .00 XXXX4454

ATOM 4455 CA VAL B 216 14. .859 39. .956 39. .997 1. .00 0. .00 XXXX4455

ATOM 4456 C VAL B 216 15. .784 39. .518 38. .870 1. .00 0. .00 XXXX4456

ATOM 4457 O VAL B 216 15. .860 38. .335 38. .537 1. .00 0. .00 XXXX4457

ATOM 4458 CB VAL B 216 13. .595 40. .607 39. .402 1. .00 0. .00 XXXX4458

ATOM 4459 CGI VAL B 216 12. .941 39. .669 38. .394 1. .00 0. .00 XXXX4459

ATOM 4460 CG2 VAL B 216 12. .618 40. .980 40. .507 1. .00 0. .00 XXXX4460

ATOM 4461 N ALA B 217 16. .490 40. .485 38. .292 1. .00 0. .00 XXXX4461

ATOM 4462 CA ALA B 217 17. .400 40. .224 37. .183 1. .00 0. .00 XXXX4462

ATOM 4463 C ALA B 217 18. .618 39. .410 37. .616 1. .00 0. .00 XXXX4463

ATOM 4464 O ALA B 217 19. .026 38. .478 36. .922 1. .00 0. .00 XXXX4464

ATOM 4465 CB ALA B 217 17. .843 41. .536 36. .547 1. .00 0. .00 XXXX4465 Attorney Docket No. 35327-522001 WO

ATOM 4466 N PHE B 218 19. .198 39. .762 38. .760 1. .00 0. .00 XXXX4466

ATOM 4467 CA PHE B 218 20. .421 39. .110 39. .220 1. .00 0. .00 XXXX4467

ATOM 4468 C PHE B 218 20. .232 37. .622 39. .499 1. .00 0. .00 XXXX4468

ATOM 4469 O PHE B 218 20. .979 36. .788 38. .987 1. .00 0. .00 XXXX4469

ATOM 4470 CB PHE B 218 20. .959 39. .791 40. .479 1. .00 0. .00 XXXX4470

ATOM 4471 CG PHE B 218 22. .097 39. .048 41. .124 1. .00 0. .00 XXXX4471

ATOM 4472 CD1 PHE B 218 23. .323 38. .950 40. .488 1. .00 0. .00 XXXX4472

ATOM 4473 CD2 PHE B 218 21. .938 38. .441 42. .359 1. .00 0. .00 XXXX4473

ATOM 4474 CE1 PHE B 218 24. .371 38. .263 41. .072 1. .00 0. .00 XXXX4474

ATOM 4475 CE2 PHE B 218 22. .984 37. .753 42. .950 1. .00 0. .00 XXXX4475

ATOM 4476 CZ PHE B 218 24. .203 37. .665 42. .305 1. .00 0. .00 XXXX4476

ATOM 4477 N PHE B 219 19. .233 37. .293 40. .311 1. .00 0. .00 XXXX4477

ATOM 4478 CA PHE B 219 19. .047 35. .917 40. .758 1. .00 0. .00 XXXX4478

ATOM 4479 C PHE B 219 18. .577 35. .011 39. .626 1. .00 0. .00 XXXX4479

ATOM 4480 O PHE B 219 18. .919 33. .829 39. .591 1. .00 0. .00 XXXX4480

ATOM 4481 CB PHE B 219 18. .066 35. .867 41. .932 1. .00 0. .00 XXXX4481

ATOM 4482 CG PHE B 219 18. .672 36. .300 43. .238 1. .00 0. .00 XXXX4482

ATOM 4483 CD1 PHE B 219 19. .511 35. .449 43. .940 1. .00 0. .00 XXXX4483

ATOM 4484 CD2 PHE B 219 18. .422 37. .561 43. .755 1. .00 0. .00 XXXX4484

ATOM 4485 CE1 PHE B 219 20. .079 35. .842 45. .138 1. .00 0. .00 XXXX4485

ATOM 4486 CE2 PHE B 219 18. .989 37. .960 44. .953 1. .00 0. .00 XXXX4486

ATOM 4487 CZ PHE B 219 19. .819 37. .099 45. .645 1. .00 0. .00 XXXX4487

ATOM 4488 N LYS B 220 17. .792 35. .559 38. .705 1. .00 0. .00 XXXX4488

ATOM 4489 CA LYS B 220 17. .381 34. .797 37. .532 1. .00 0. .00 XXXX4489

ATOM 4490 C LYS B 220 18. .582 34. .509 36. .639 1. .00 0. .00 XXXX4490

ATOM 4491 O LYS B 220 18. .762 33. .386 36. .168 1. .00 0. .00 XXXX4491

ATOM 4492 CB LYS B 220 16. .296 35. .538 36. .746 1. .00 0. .00 XXXX4492

ATOM 4493 CG LYS B 220 14. .942 35. .550 37. .437 1. .00 0. .00 XXXX4493

ATOM 4494 CD LYS B 220 13. .859 36. .123 36. .539 1. .00 0. .00 XXXX4494

ATOM 4495 CE LYS B 220 12. .523 36. .198 37. .265 1. .00 0. .00 XXXX4495

ATOM 4496 NZ LYS B 220 11. .459 36. .800 36. .415 1. .00 0. .00 XXXX4496

ATOM 4497 N GLN B 221 19. .403 35. .529 36. .410 1. .00 0. .00 XXXX4497

ATOM 4498 CA GLN B 221 20. .580 35. .384 35. .560 1. .00 0. .00 XXXX4498

ATOM 4499 C GLN B 221 21. .650 34. .531 36. .235 1. .00 0. .00 XXXX4499

ATOM 4500 O GLN B 221 22. .424 33. .847 35. .565 1. .00 0. .00 XXXX4500

ATOM 4501 CB GLN B 221 21. .148 36. .757 35. .190 1. .00 0. .00 XXXX4501

ATOM 4502 CG GLN B 221 20. .354 37. .484 34. .110 1. .00 0. .00 XXXX4502

ATOM 4503 CD GLN B 221 20. .734 38. .948 33. .986 1. .00 0. .00 XXXX4503

ATOM 4504 OE1 GLN B 221 21. .915 39. .295 33. .963 1. .00 0. .00 XXXX4504

ATOM 4505 NE2 GLN B 221 19. .731 39. .815 33. .901 1. .00 0. .00 XXXX4505

ATOM 4506 N LEU B 222 21. .691 34. .577 37. .563 1. .00 0. .00 XXXX4506

ATOM 4507 CA LEU B 222 22. .634 33. .767 38. .326 1. .00 0. .00 XXXX4507

ATOM 4508 C LEU B 222 22. .363 32. .275 38. .142 1. .00 0. .00 XXXX4508

ATOM 4509 O LEU B 222 23. .276 31. .499 37. .857 1. .00 0. .00 XXXX4509

ATOM 4510 CB LEU B 222 22. .572 34. .130 39. .811 1. .00 0. .00 XXXX4510

ATOM 4511 CG LEU B 222 23. .600 33. .436 40. .708 1. .00 0. .00 XXXX4511

ATOM 4512 CD1 LEU B 222 25. .014 33. .856 40. .328 1. .00 0. .00 XXXX4512

ATOM 4513 CD2 LEU B 222 23. .320 33. .716 42. .179 1. .00 0. .00 XXXX4513

ATOM 4514 N LYS B 223 21. .104 31. .882 38. .301 1. .00 0. .00 XXXX4514

ATOM 4515 CA LYS B 223 20. .712 30. .488 38. .125 1. .00 0. .00 XXXX4515

ATOM 4516 C LYS B 223 20. .885 30. .045 36. .674 1. .00 0. .00 XXXX4516

ATOM 4517 O LYS B 223 21. .340 28. .933 36. .408 1. .00 0. .00 XXXX4517

ATOM 4518 CB LYS B 223 19. .266 30. .272 38. .577 1. .00 0. .00 XXXX4518

ATOM 4519 CG LYS B 223 18. .809 28. .825 38. .494 1. .00 0. .00 XXXX4519

ATOM 4520 CD LYS B 223 17. .380 28. .661 38. .982 1. .00 0. .00 XXXX4520

ATOM 4521 CE LYS B 223 16. .917 27. .218 38. .850 1. .00 0. .00 XXXX4521

ATOM 4522 NZ LYS B 223 17. .794 26. .280 39. .608 1. .00 0. .00 XXXX4522

ATOM 4523 N ASP B 224 20. .516 30. .914 35. .738 1. .00 0. .00 XXXX4523

ATOM 4524 CA ASP B 224 20. .619 30. .588 34. .320 1. .00 0. .00 XXXX4524

ATOM 4525 C ASP B 224 22. .081 30. .480 33. .903 1. .00 0. .00 XXXX4525

ATOM 4526 O ASP B 224 22. .403 29. .846 32. .899 1. .00 0. .00 XXXX4526

ATOM 4527 CB ASP B 224 19. .906 31. .638 33. .465 1. .00 0. .00 XXXX4527

ATOM 4528 CG ASP B 224 18. .399 31. .600 33. .628 1. .00 0. .00 XXXX4528

ATOM 4529 OD1 ASP B 224 17. .886 30. .628 34. .222 1. .00 0. .00 XXXX4529

ATOM 4530 OD2 ASP B 224 17. .727 32. .543 33. .159 1. .00 0. .00 XXXX4530

ATOM 4531 N ALA B 225 22. .960 31. .105 34. .680 1. .00 0. .00 XXXX4531

ATOM 4532 CA ALA B 225 24. .396 31. .025 34. .436 1. .00 0. .00 XXXX4532 Attorney Docket No. 35327-522001 WO

ATOM 4533 C ALA B 225 24. .989 29. .755 35. .040 1. .00 0. .00 XXXX4533

ATOM 4534 O ALA B 225 26. .196 29. .527 34. .967 1. .00 0. .00 XXXX4534

ATOM 4535 CB ALA B 225 25. .097 32. .257 34. .992 1. .00 0. .00 XXXX4535

ATOM 4536 N GLY B 226 24. .132 28. .930 35. .635 1. .00 0. .00 XXXX4536

ATOM 4537 CA GLY B 226 24. .544 27. .637 36. .151 1. .00 0. .00 XXXX4537

ATOM 4538 C GLY B 226 25. .025 27. .636 37. .591 1. .00 0. .00 XXXX4538

ATOM 4539 O GLY B 226 25. .616 26. .659 38. .049 1. .00 0. .00 XXXX4539

ATOM 4540 N ILE B 227 24. .784 28. .730 38. .308 1. .00 0. .00 XXXX4540

ATOM 4541 CA ILE B 227 25. .192 28. .817 39. .707 1. .00 0. .00 XXXX4541

ATOM 4542 C ILE B 227 24. .015 28. .632 40. .666 1. .00 0. .00 XXXX4542

ATOM 4543 O ILE B 227 23. .060 29. .407 40. .638 1. .00 0. .00 XXXX4543

ATOM 4544 CB ILE B 227 25. .861 30. .171 40. .007 1. .00 0. .00 XXXX4544

ATOM 4545 CGI ILE B 227 27. .127 30. .341 39. .164 1. .00 0. .00 XXXX4545

ATOM 4546 CD1 ILE B 227 27. .682 31. .748 39. .179 1. .00 0. .00 XXXX4546

ATOM 4547 CG2 ILE B 227 26. .173 30. .294 41. .493 1. .00 0. .00 XXXX4547

ATOM 4548 N ASP B 228 24. .083 27. .602 41. .506 1. .00 0. .00 XXXX4548

ATOM 4549 CA ASP B 228 23. .059 27. .380 42. .528 1. .00 0. .00 XXXX4549

ATOM 4550 C ASP B 228 23. .613 27. .589 43. .940 1. .00 0. .00 XXXX4550

ATOM 4551 O ASP B 228 24. .819 27. .754 44. .126 1. .00 0. .00 XXXX4551

ATOM 4552 CB ASP B 228 22. .429 25. .985 42. .385 1. .00 0. .00 XXXX4552

ATOM 4553 CG ASP B 228 23. .423 24. .851 42. .583 1. .00 0. .00 XXXX4553

ATOM 4554 OD1 ASP B 228 24. .532 25. .082 43. .108 1. .00 0. .00 XXXX4554

ATOM 4555 OD2 ASP B 228 23. .081 23. .709 42. .210 1. .00 0. .00 XXXX4555

ATOM 4556 N ALA B 229 22. .721 27. .580 44. .925 1. .00 0. .00 XXXX4556

ATOM 4557 CA ALA B 229 23. .078 27. .882 46. .309 1. .00 0. .00 XXXX4557

ATOM 4558 C ALA B 229 24. .057 26. .873 46. .911 1. .00 0. .00 XXXX4558

ATOM 4559 O ALA B 229 24. .769 27. .188 47. .864 1. .00 0. .00 XXXX4559

ATOM 4560 CB ALA B 229 21. .821 27. .960 47. .164 1. .00 0. .00 XXXX4560

ATOM 4561 N ASN B 230 24. .093 25. .663 46. .362 1. .00 0. .00 XXXX4561

ATOM 4562 CA ASN B 230 25. .020 24. .646 46. .855 1. .00 0. .00 XXXX4562

ATOM 4563 C ASN B 230 26. .466 24. .995 46. .520 1. .00 0. .00 XXXX4563

ATOM 4564 O ASN B 230 27. .359 24. .849 47. .355 1. .00 0. .00 XXXX4564

ATOM 4565 CB ASN B 230 24. .674 23. .274 46. .267 1. .00 0. .00 XXXX4565

ATOM 4566 CG ASN B 230 23. .417 22. .679 46. .871 1. .00 0. .00 XXXX4566

ATOM 4567 OD1 ASN B 230 23. .147 22. .844 48. .061 1. .00 0. .00 XXXX4567

ATOM 4568 ND2 ASN B 230 22. .642 21. .979 46. .051 1. .00 0. .00 XXXX4568

ATOM 4569 N THR B 231 26. .687 25. .453 45. .293 1. .00 0. .00 XXXX4569

ATOM 4570 CA THR B 231 28. .019 25. .842 44. .843 1. .00 0. .00 XXXX4570

ATOM 4571 C THR B 231 28. .454 27. .196 45. .404 1. .00 0. .00 XXXX4571

ATOM 4572 O THR B 231 29. .598 27. .365 45. .826 1. .00 0. .00 XXXX4572

ATOM 4573 CB THR B 231 28. .093 25. .898 43. .305 1. .00 0. .00 XXXX4573

ATOM 4574 OG1 THR B 231 27. .668 24. .644 42. .757 1. .00 0. .00 XXXX4574

ATOM 4575 CG2 THR B 231 29. .513 26. .184 42. .852 1. .00 0. .00 XXXX4575

ATOM 4576 N LEU B 232 27. .535 28. .156 45. .405 1. .00 0. .00 XXXX4576

ATOM 4577 CA LEU B 232 27. .832 29. .504 45. .879 1. .00 0. .00 XXXX4577

ATOM 4578 C LEU B 232 26. .634 30. .149 46. .566 1. .00 0. .00 XXXX4578

ATOM 4579 O LEU B 232 25. .745 30. .681 45. .901 1. .00 0. .00 XXXX4579

ATOM 4580 CB LEU B 232 28. .300 30. .384 44. .719 1. .00 0. .00 XXXX4580

ATOM 4581 CG LEU B 232 28. .616 31. .839 45. .073 1. .00 0. .00 XXXX4581

ATOM 4582 CD1 LEU B 232 29. .656 31. .915 46. .182 1. .00 0. .00 XXXX4582

ATOM 4583 CD2 LEU B 232 29. .072 32. .612 43. .842 1. .00 0. .00 XXXX4583

ATOM 4584 N PRO B 233 26. .605 30. .102 47. .904 1. .00 0. .00 XXXX4584

ATOM 4585 CA PRO B 233 25. .507 30. .721 48. .651 1. .00 0. .00 XXXX4585

ATOM 4586 C PRO B 233 25. .532 32. .243 48. .549 1. .00 0. .00 XXXX4586

ATOM 4587 O PRO B 233 26. .605 32. .849 48. .561 1. .00 0. .00 XXXX4587

ATOM 4588 CB PRO B 233 25. .756 30. .269 50. .094 1. .00 0. .00 XXXX4588

ATOM 4589 CG PRO B 233 27. .196 29. .892 50. .144 1. .00 0. .00 XXXX4589

ATOM 4590 CD PRO B 233 27. .562 29. .404 48. .780 1. .00 0. .00 XXXX4590

ATOM 4591 N VAL B 234 24. .352 32. .845 48. .437 1. .00 0. .00 XXXX4591

ATOM 4592 CA VAL B 234 24. .217 34. .295 48. .446 1. .00 0. .00 XXXX4592

ATOM 4593 C VAL B 234 23. .498 34. .754 49. .710 1. .00 0. .00 XXXX4593

ATOM 4594 O VAL B 234 22. .367 34. .342 49. .974 1. .00 0. .00 XXXX4594

ATOM 4595 CB VAL B 234 23. .446 34. .804 47. .214 1. .00 0. .00 XXXX4595

ATOM 4596 CGI VAL B 234 23. .275 36. .317 47. .283 1. .00 0. .00 XXXX4596

ATOM 4597 CG2 VAL B 234 24. .156 34. .390 45. .929 1. .00 0. .00 XXXX4597

ATOM 4598 N MET B 235 24. .156 35. .605 50. .490 1. .00 0. .00 XXXX4598

ATOM 4599 CA MET B 235 23. .531 36. .200 51. .666 1. .00 0. .00 XXXX4599 Attorney Docket No. 35327-522001 WO

ATOM 4600 C MET B 235 22. .987 37. .583 51. .332 1. .00 0. .00 XXXX4600

ATOM 4601 O MET B 235 23. .736 38. .472 50. .927 1. .00 0. .00 XXXX4601

ATOM 4602 CB MET B 235 24. .528 36. .287 52. .824 1. .00 0. .00 XXXX4602

ATOM 4603 CG MET B 235 24. .020 37. .068 54. .029 1. .00 0. .00 XXXX4603

ATOM 4604 SD MET B 235 22. .682 36. .240 54. .913 1. .00 0. .00 XXXX4604

ATOM 4605 CE MET B 235 23. .577 34. .965 55. .798 1. .00 0. .00 XXXX4605

ATOM 4606 N SER B 236 21. .681 37. .756 51. .505 1. .00 0. .00 XXXX4606

ATOM 4607 CA SER B 236 21. .019 39. .012 51. .174 1. .00 0. .00 XXXX4607

ATOM 4608 C SER B 236 20. .482 39. .699 52. .424 1. .00 0. .00 XXXX4608

ATOM 4609 O SER B 236 20. .066 39. .037 53. .374 1. .00 0. .00 XXXX4609

ATOM 4610 CB SER B 236 19. .881 38. .768 50. .181 1. .00 0. .00 XXXX4610

ATOM 4611 OG SER B 236 20. .374 38. .250 48. .958 1. .00 0. .00 XXXX4611

ATOM 4612 N VAL B 237 20. .491 41. .029 52. .419 1. .00 0. .00 XXXX4612

ATOM 4613 CA VAL B 237 20. .001 41. .790 53. .562 1. .00 0. .00 XXXX4613

ATOM 4614 C VAL B 237 18. .934 42. .821 53. .194 1. .00 0. .00 XXXX4614

ATOM 4615 O VAL B 237 18. .449 43. .542 54. .063 1. .00 0. .00 XXXX4615

ATOM 4616 CB VAL B 237 21. .155 42. .519 54. .281 1. .00 0. .00 XXXX4616

ATOM 4617 CGI VAL B 237 22. .074 41. .517 54. .970 1. .00 0. .00 XXXX4617

ATOM 4618 CG2 VAL B 237 21. .928 43. .385 53. .299 1. .00 0. .00 XXXX4618

ATOM 4619 N SER B 238 18. .566 42. .895 51. .918 1. .00 0. .00 XXXX4619

ATOM 4620 CA SER B 238 17. .566 43. .869 51. .487 1. .00 0. .00 XXXX4620

ATOM 4621 C SER B 238 16. .432 43. .230 50. .692 1. .00 0. .00 XXXX4621

ATOM 4622 O SER B 238 15. .631 43. .928 50. .068 1. .00 0. .00 XXXX4622

ATOM 4623 CB SER B 238 18. .220 44. .979 50. .660 1. .00 0. .00 XXXX4623

ATOM 4624 OG SER B 238 19. .195 45. .675 51. .420 1. .00 0. .00 XXXX4624

ATOM 4625 N ILE B 239 16. .366 41. .903 50. .717 1. .00 0. .00 XXXX4625

ATOM 4626 CA ILE B 239 15. .205 41. .192 50. .196 1. .00 0. .00 XXXX4626

ATOM 4627 C ILE B 239 14. .707 40. .188 51. .227 1. .00 0. .00 XXXX4627

ATOM 4628 O ILE B 239 15. .492 39. .623 51. .989 1. .00 0. .00 XXXX4628

ATOM 4629 CB ILE B 239 15. .510 40. .449 48. .878 1. .00 0. .00 XXXX4629

ATOM 4630 CGI ILE B 239 16. .614 39. .410 49. .083 1. .00 0. .00 XXXX4630

ATOM 4631 CG2 ILE B 239 15. .865 41. .438 47. .771 1. .00 0. .00 XXXX4631

ATOM 4632 CD1 ILE B 239 16. .690 38. .383 47. .977 1. .00 0. .00 XXXX4632

ATOM 4633 N ALA B 240 13. .398 39. .970 51. .243 1. .00 0. .00 XXXX4633

ATOM 4634 CA ALA B 240 12. .792 38. .995 52. .138 1. .00 0. .00 XXXX4634

ATOM 4635 C ALA B 240 11. .644 38. .290 51. .423 1. .00 0. .00 XXXX4635

ATOM 4636 O ALA B 240 11. .623 38. .231 50. .191 1. .00 0. .00 XXXX4636

ATOM 4637 CB ALA B 240 12. .307 39. .666 53. .417 1. .00 0. .00 XXXX4637

ATOM 4638 N GLU B 241 10. .700 37. .756 52. .192 1. .00 0. .00 XXXX4638

ATOM 4639 CA GLU B 241 9. .616 36. .943 51. .640 1. .00 0. .00 XXXX4639

ATOM 4640 C GLU B 241 8. .847 37. .637 50. .516 1. .00 0. .00 XXXX4640

ATOM 4641 O GLU B 241 8. .434 36. .992 49. .553 1. .00 0. .00 XXXX4641

ATOM 4642 CB GLU B 241 8. .638 36. .534 52. .747 1. .00 0. .00 XXXX4642

ATOM 4643 CG GLU B 241 9. .152 35. .429 53. .660 1. .00 0. .00 XXXX4643

ATOM 4644 CD GLU B 241 9. .861 35. .960 54. .891 1. .00 0. .00 XXXX4644

ATOM 4645 OE1 GLU B 241 10. .489 37. .036 54. .801 1. .00 0. .00 XXXX4645

ATOM 4646 OE2 GLU B 241 9. .790 35. .300 55. .950 1. .00 0. .00 XXXX4646

ATOM 4647 N GLU B 242 8. .651 38. .945 50. .639 1. .00 0. .00 XXXX4647

ATOM 4648 CA GLU B 242 7. .898 39. .681 49. .628 1. .00 0. .00 XXXX4648

ATOM 4649 C GLU B 242 8. .626 39. .678 48. .288 1. .00 0. .00 XXXX4649

ATOM 4650 O GLU B 242 8. .048 39. .326 47. .258 1. .00 0. .00 XXXX4650

ATOM 4651 CB GLU B 242 7. .640 41. .119 50. .079 1. .00 0. .00 XXXX4651

ATOM 4652 CG GLU B 242 6. .948 41. .973 49. .029 1. .00 0. .00 XXXX4652

ATOM 4653 CD GLU B 242 5. .509 41. .554 48. .783 1. .00 0. .00 XXXX4653

ATOM 4654 OE1 GLU B 242 5. .001 40. .684 49. .523 1. .00 0. .00 XXXX4654

ATOM 4655 OE2 GLU B 242 4. .884 42. .096 47. .847 1. .00 0. .00 XXXX4655

ATOM 4656 N GLU B 243 9. .896 40. .071 48. .308 1. .00 0. .00 XXXX4656

ATOM 4657 CA GLU B 243 10. .703 40. .112 47. .094 1. .00 0. .00 XXXX4657

ATOM 4658 C GLU B 243 10. .998 38. .712 46. .567 1. .00 0. .00 XXXX4658

ATOM 4659 O GLU B 243 11. .086 38. .504 45. .358 1. .00 0. .00 XXXX4659

ATOM 4660 CB GLU B 243 12. .013 40. .864 47. .341 1. .00 0. .00 XXXX4660

ATOM 4661 CG GLU B 243 11. .836 42. .325 47. .733 1. .00 0. .00 XXXX4661

ATOM 4662 CD GLU B 243 11. .431 42. .499 49. .183 1. .00 0. .00 XXXX4662

ATOM 4663 OE1 GLU B 243 11. .456 41. .500 49. .933 1. .00 0. .00 XXXX4663

ATOM 4664 OE2 GLU B 243 11. .086 43. .636 49. .572 1. .00 0. .00 XXXX4664

ATOM 4665 N ILE B 244 11. .153 37. .757 47. .480 1. .00 0. .00 XXXX4665

ATOM 4666 CA ILE B 244 11. .414 36. .372 47. .104 1. .00 0. .00 XXXX4666 Attorney Docket No. 35327-522001 WO

ATOM 4667 C ILE B 244 10. .272 35. .812 46. .260 1. .00 0. .00 XXXX4667

ATOM 4668 O ILE B 244 10. .502 35. .096 45. .285 1. .00 0. .00 XXXX4668

ATOM 4669 CB ILE B 244 11. .622 35. .478 48. .342 1. .00 0. .00 XXXX4669

ATOM 4670 CGI ILE B 244 12. .949 35. .818 49. .028 1. .00 0. .00 XXXX4670

ATOM 4671 CG2 ILE B 244 11. .597 34. .011 47. .949 1. .00 0. .00 XXXX4671

ATOM 4672 CD1 ILE B 244 13. .124 35. .162 50. .384 1. .00 0. .00 XXXX4672

ATOM 4673 N LYS B 245 9. .041 36. .143 46. .638 1. .00 0. .00 XXXX4673

ATOM 4674 CA LYS B 245 7. .872 35. .733 45. .867 1. .00 0. .00 XXXX4674

ATOM 4675 C LYS B 245 7. .815 36. .420 44. .508 1. .00 0. .00 XXXX4675

ATOM 4676 O LYS B 245 7. .418 35. .812 43. .515 1. .00 0. .00 XXXX4676

ATOM 4677 CB LYS B 245 6. .588 36. .019 46. .648 1. .00 0. .00 XXXX4677

ATOM 4678 CG LYS B 245 5. .980 34. .792 47. .295 1. .00 0. .00 XXXX4678

ATOM 4679 CD LYS B 245 5. .645 33. .753 46. .237 1. .00 0. .00 XXXX4679

ATOM 4680 CE LYS B 245 4. .934 32. .551 46. .831 1. .00 0. .00 XXXX4680

ATOM 4681 NZ LYS B 245 4. .621 31. .534 45. .788 1. .00 0. .00 XXXX4681

ATOM 4682 N GLY B 246 8. .211 37. .688 44. .469 1. .00 0. .00 XXXX4682

ATOM 4683 CA GLY B 246 8. .228 38. .440 43. .228 1. .00 0. .00 XXXX4683

ATOM 4684 C GLY B 246 9. .284 37. .923 42. .272 1. .00 0. .00 XXXX4684

ATOM 4685 O GLY B 246 9. .045 37. .795 41. .072 1. .00 0. .00 XXXX4685

ATOM 4686 N ILE B 247 10. .460 37. .624 42. .812 1. .00 0. .00 XXXX4686

ATOM 4687 CA ILE B 247 11. .567 37. .113 42. .011 1. .00 0. .00 XXXX4687

ATOM 4688 C ILE B 247 11. .298 35. .684 41. .549 1. .00 0. .00 XXXX4688

ATOM 4689 O ILE B 247 11. .607 35. .317 40. .415 1. .00 0. .00 XXXX4689

ATOM 4690 CB ILE B 247 12. .889 37. .145 42. .799 1. .00 0. .00 XXXX4690

ATOM 4691 CGI ILE B 247 13. .215 38. .573 43. .240 1. .00 0. .00 XXXX4691

ATOM 4692 CG2 ILE B 247 14. .022 36. .559 41. .968 1. .00 0. .00 XXXX4692

ATOM 4693 CD1 ILE B 247 14. .339 38. .656 44. .250 1. .00 0. .00 XXXX4693

ATOM 4694 N GLY B 248 10. .714 34. .885 42. .435 1. .00 0. .00 XXXX4694

ATOM 4695 CA GLY B 248 10. .502 33. .474 42. .169 1. .00 0. .00 XXXX4695

ATOM 4696 C GLY B 248 11. .397 32. .615 43. .039 1. .00 0. .00 XXXX4696

ATOM 4697 O GLY B 248 12. .616 32. .630 42. .883 1. .00 0. .00 XXXX4697

ATOM 4698 N PRO B 249 10. .793 31. .860 43. .969 1. .00 0. .00 XXXX4698

ATOM 4699 CA PRO B 249 11. .519 30. .997 44. .909 1. .00 0. .00 XXXX4699

ATOM 4700 C PRO B 249 12. .438 29. .983 44. .224 1. .00 0. .00 XXXX4700

ATOM 4701 O PRO B 249 13. .409 29. .534 44. .833 1. .00 0. .00 XXXX4701

ATOM 4702 CB PRO B 249 10. .392 30. .283 45. .663 1. .00 0. .00 XXXX4702

ATOM 4703 CG PRO B 249 9. .239 31. .226 45. .582 1. .00 0. .00 XXXX4703

ATOM 4704 CD PRO B 249 9. .341 31. .847 44. .220 1. .00 0. .00 XXXX4704

ATOM 4705 N GLU B 250 12. .139 29. .628 42. .978 1. .00 0. .00 XXXX4705

ATOM 4706 CA GLU B 250 12. .962 28. .667 42. .250 1. .00 0. .00 XXXX4706

ATOM 4707 C GLU B 250 14. .374 29. .202 42. .024 1. .00 0. .00 XXXX4707

ATOM 4708 O GLU B 250 15. .320 28. .432 41. .851 1. .00 0. .00 XXXX4708

ATOM 4709 CB GLU B 250 12. .321 28. .310 40. .905 1. .00 0. .00 XXXX4709

ATOM 4710 CG GLU B 250 12. .314 29. .445 39. .891 1. .00 0. .00 XXXX4710

ATOM 4711 CD GLU B 250 11. .633 29. .061 38. .590 1. .00 0. .00 XXXX4711

ATOM 4712 OE1 GLU B 250 12. .214 28. .261 37. .826 1. .00 0. .00 XXXX4712

ATOM 4713 OE2 GLU B 250 10. .517 29. .560 38. .329 1. .00 0. .00 XXXX4713

ATOM 4714 N TYR B 251 14. .510 30. .525 42. .024 1. .00 0. .00 XXXX4714

ATOM 4715 CA TYR B 251 15. .807 31. .163 41. .827 1. .00 0. .00 XXXX4715

ATOM 4716 C TYR B 251 16. .511 31. .468 43. .145 1. .00 0. .00 XXXX4716

ATOM 4717 O TYR B 251 17. .684 31. .845 43. .156 1. .00 0. .00 XXXX4717

ATOM 4718 CB TYR B 251 15. .642 32. .457 41. .025 1. .00 0. .00 XXXX4718

ATOM 4719 CG TYR B 251 15. .003 32. .266 39. .669 1. .00 0. .00 XXXX4719

ATOM 4720 CD1 TYR B 251 15. .714 31. .704 38. .618 1. .00 0. .00 XXXX4720

ATOM 4721 CD2 TYR B 251 13. .687 32. .649 39. .439 1. .00 0. .00 XXXX4721

ATOM 4722 CE1 TYR B 251 15. .134 31. .527 37. .375 1. .00 0. .00 XXXX4722

ATOM 4723 CE2 TYR B 251 13. .097 32. .476 38. .200 1. .00 0. .00 XXXX4723

ATOM 4724 CZ TYR B 251 13. .826 31. .915 37. .172 1. .00 0. .00 XXXX4724

ATOM 4725 OH TYR B 251 13. .245 31. .742 35. .937 1. .00 0. .00 XXXX4725

ATOM 4726 N LEU B 252 15. .795 31. .306 44. .252 1. .00 0. .00 XXXX4726

ATOM 4727 CA LEU B 252 16. .313 31. .721 45. .550 1. .00 0. .00 XXXX4727

ATOM 4728 C LEU B 252 16. .482 30. .579 46. .548 1. .00 0. .00 XXXX4728

ATOM 4729 O LEU B 252 17. .126 30. .752 47. .583 1. .00 0. .00 XXXX4729

ATOM 4730 CB LEU B 252 15. .402 32. .797 46. .144 1. .00 0. .00 XXXX4730

ATOM 4731 CG LEU B 252 15. .752 34. .219 45. .696 1. .00 0. .00 XXXX4731

ATOM 4732 CD1 LEU B 252 14. .568 35. .161 45. .866 1. .00 0. .00 XXXX4732

ATOM 4733 CD2 LEU B 252 16. .968 34. .735 46. .458 1. .00 0. .00 XXXX4733 Attorney Docket No. 35327-522001 WO

ATOM 4734 N LYS B 253 15. .893 29. .424 46. .248 1. .00 0. .00 XXXX4734

ATOM 4735 CA LYS B 253 15. .918 28. .286 47. .167 1. .00 0. .00 XXXX4735

ATOM 4736 C LYS B 253 17. .340 27. .919 47. .588 1. .00 0. .00 XXXX4736

ATOM 4737 O LYS B 253 18. .209 27. .696 46. .745 1. .00 0. .00 XXXX4737

ATOM 4738 CB LYS B 253 15. .232 27. .067 46. .544 1. .00 0. .00 XXXX4738

ATOM 4739 CG LYS B 253 15. .146 25. .872 47. .487 1. .00 0. .00 XXXX4739

ATOM 4740 CD LYS B 253 14. .561 24. .640 46. .809 1. .00 0. .00 XXXX4740

ATOM 4741 CE LYS B 253 15. .537 24. .026 45. .819 1. .00 0. .00 XXXX4741

ATOM 4742 NZ LYS B 253 15. .073 22. .689 45. .351 1. .00 0. .00 XXXX4742

ATOM 4743 N GLY B 254 17. .566 27. .859 48. .897 1. .00 0. .00 XXXX4743

ATOM 4744 CA GLY B 254 18. .859 27. .478 49. .437 1. .00 0. .00 XXXX4744

ATOM 4745 C GLY B 254 19. .753 28. .658 49. .767 1. .00 0. .00 XXXX4745

ATOM 4746 O GLY B 254 20. .732 28. .516 50. .500 1. .00 0. .00 XXXX4746

ATOM 4747 N HIS B 255 19. .424 29. .825 49. .224 1. .00 0. .00 XXXX4747

ATOM 4748 CA HIS B 255 20. .189 31. .032 49. .510 1. .00 0. .00 XXXX4748

ATOM 4749 C HIS B 255 19. .804 31. .595 50. .876 1. .00 0. .00 XXXX4749

ATOM 4750 O HIS B 255 18. .862 31. .116 51. .508 1. .00 0. .00 XXXX4750

ATOM 4751 CB HIS B 255 19. .989 32. .070 48. .404 1. .00 0. .00 XXXX4751

ATOM 4752 CG HIS B 255 20. .710 31. .735 47. .135 1. .00 0. .00 XXXX4752

ATOM 4753 ND1 HIS B 255 22. .083 31. .628 47. .066 1. .00 0. .00 XXXX4753

ATOM 4754 CD2 HIS B 255 20. .250 31. .470 45. .889 1. .00 0. .00 XXXX4754

ATOM 4755 CE1 HIS B 255 22. .438 31. .318 45. .832 1. .00 0. .00 XXXX4755

ATOM 4756 NE2 HIS B 255 21. .344 31. .216 45. .098 1. .00 0. .00 XXXX4756

ATOM 4757 N LEU B 256 20. .528 32. .615 51. .325 1. .00 0. .00 XXXX4757

ATOM 4758 CA LEU B 256 20. .465 33. .031 52. .723 1. .00 0. .00 XXXX4758

ATOM 4759 C LEU B 256 19. .976 34. .462 52. .924 1. .00 0. .00 XXXX4759

ATOM 4760 O LEU B 256 20. .163 35. .324 52. .066 1. .00 0. .00 XXXX4760

ATOM 4761 CB LEU B 256 21. .845 32. .882 53. .369 1. .00 0. .00 XXXX4761

ATOM 4762 CG LEU B 256 22. .514 31. .511 53. .260 1. .00 0. .00 XXXX4762

ATOM 4763 CD1 LEU B 256 23. .947 31. .573 53. .766 1. .00 0. .00 XXXX4763

ATOM 4764 CD2 LEU B 256 21. .720 30. .457 54. .018 1. .00 0. .00 XXXX4764

ATOM 4765 N VAL B 257 19. .349 34. .700 54. .072 1. .00 0. .00 XXXX4765

ATOM 4766 CA VAL B 257 18. .953 36. .044 54. .474 1. .00 0. .00 XXXX4766

ATOM 4767 C VAL B 257 19. .240 36. .275 55. .953 1. .00 0. .00 XXXX4767

ATOM 4768 O VAL B 257 19. .315 35. .328 56. .736 1. .00 0. .00 XXXX4768

ATOM 4769 CB VAL B 257 17. .457 36. .304 54. .214 1. .00 0. .00 XXXX4769

ATOM 4770 CGI VAL B 257 17. .146 36. .206 52. .726 1. .00 0. .00 XXXX4770

ATOM 4771 CG2 VAL B 257 16. .601 35. .331 55. .015 1. .00 0. .00 XXXX4771

ATOM 4772 N THR B 258 19. .400 37. .541 56. .327 1. .00 0. .00 XXXX4772

ATOM 4773 CA THR B 258 19. .479 37. .926 57. .731 1. .00 0. .00 XXXX4773

ATOM 4774 C THR B 258 18. .492 39. .053 58. .014 1. .00 0. .00 XXXX4774

ATOM 4775 O THR B 258 18. .488 40. .075 57. .330 1. .00 0. .00 XXXX4775

ATOM 4776 CB THR B 258 20. .901 38. .372 58. .129 1. .00 0. .00 XXXX4776

ATOM 4777 OG1 THR B 258 21. .828 37. .309 57. .879 1. .00 0. .00 XXXX4777

ATOM 4778 CG2 THR B 258 20. .951 38. .740 59. .606 1. .00 0. .00 XXXX4778

ATOM 4779 N TRP B 259 17. .656 38. .856 59. .026 1. .00 0. .00 XXXX4779

ATOM 4780 CA TRP B 259 16. .639 39. .833 59. .390 1. .00 0. .00 XXXX4780

ATOM 4781 C TRP B 259 16. .351 39. .754 60. .883 1. .00 0. .00 XXXX4781

ATOM 4782 O TRP B 259 17. .076 39. .099 61. .633 1. .00 0. .00 XXXX4782

ATOM 4783 CB TRP B 259 15. .349 39. .601 58. .596 1. .00 0. .00 XXXX4783

ATOM 4784 CG TRP B 259 15. .444 39. .931 57. .132 1. .00 0. .00 XXXX4784

ATOM 4785 CD1 TRP B 259 15. .646 39. .053 56. .107 1. .00 0. .00 XXXX4785

ATOM 4786 CD2 TRP B 259 15. .312 41. .226 56. .529 1. .00 0. .00 XXXX4786

ATOM 4787 NE1 TRP B 259 15. .663 39. .722 54. .906 1. .00 0. .00 XXXX4787

ATOM 4788 CE2 TRP B 259 15. .457 41. .056 55. .138 1. .00 0. .00 XXXX4788

ATOM 4789 CE3 TRP B 259 15. .091 42. .511 57. .032 1. .00 0. .00 XXXX4789

ATOM 4790 CZ2 TRP B 259 15. .388 42. .123 54. .245 1. .00 0. .00 XXXX4790

ATOM 4791 CZ3 TRP B 259 15. .021 43. .569 56. .143 1. .00 0. .00 XXXX4791

ATOM 4792 CH2 TRP B 259 15. .171 43. .368 54. .766 1. .00 0. .00 XXXX4792

ATOM 4793 N ASN B 260 15. .287 40. .423 61. .310 1. .00 0. .00 XXXX4793

ATOM 4794 CA ASN B 260 14. .851 40. .351 62. .697 1. .00 0. .00 XXXX4794

ATOM 4795 C ASN B 260 13. .545 39. .581 62. .789 1. .00 0. .00 XXXX4795

ATOM 4796 O ASN B 260 13. .052 39. .288 63. .880 1. .00 0. .00 XXXX4796

ATOM 4797 CB ASN B 260 14. .683 41. .750 63. .289 1. .00 0. .00 XXXX4797

ATOM 4798 CG ASN B 260 15. .913 42. .614 63. .104 1. .00 0. .00 XXXX4798

ATOM 4799 OD1 ASN B 260 15. .853 43. .674 62. .481 1. .00 0. .00 XXXX4799

ATOM 4800 ND2 ASN B 260 17. .039 42. .164 63. .645 1. .00 0. .00 XXXX4800 Attorney Docket No. 35327-522001 WO

ATOM 4801 N TYR B 261 12. .992 39. .256 61. .625 1. .00 0. .00 XXXX4801

ATOM 4802 CA TYR B 261 11. .677 38. .639 61. .538 1. .00 0. .00 XXXX4802

ATOM 4803 C TYR B 261 11. .530 37. .796 60. .276 1. .00 0. .00 XXXX4803

ATOM 4804 O TYR B 261 11. .995 38. .179 59. .201 1. .00 0. .00 XXXX4804

ATOM 4805 CB TYR B 261 10. .589 39. .718 61. .581 1. .00 0. .00 XXXX4805

ATOM 4806 CG TYR B 261 9. .197 39. .222 61. .243 1. .00 0. .00 XXXX4806

ATOM 4807 CD1 TYR B 261 8. .745 39. .199 59. .929 1. .00 0. .00 XXXX4807

ATOM 4808 CD2 TYR B 261 8. .334 38. .785 62. .239 1. .00 0. .00 XXXX4808

ATOM 4809 CE1 TYR B 261 7. .475 38. .747 59. .617 1. .00 0. .00 XXXX4809

ATOM 4810 CE2 TYR B 261 7. .062 38. .332 61. .937 1. .00 0. .00 XXXX4810

ATOM 4811 CZ TYR B 261 6. .637 38. .316 60. .625 1. .00 0. .00 XXXX4811

ATOM 4812 OH TYR B 261 5. .371 37. .866 60. .321 1. .00 0. .00 XXXX4812

ATOM 4813 N PHE B 262 10. .873 36. .651 60. .426 1. .00 0. .00 XXXX4813

ATOM 4814 CA PHE B 262 10. .430 35. .839 59. .300 1. .00 0. .00 XXXX4814

ATOM 4815 C PHE B 262 8. .943 35. .566 59. .466 1. .00 0. .00 XXXX4815

ATOM 4816 O PHE B 262 8. .433 35. .541 60. .587 1. .00 0. .00 XXXX4816

ATOM 4817 CB PHE B 262 11. .196 34. .511 59. .214 1. .00 0. .00 XXXX4817

ATOM 4818 CG PHE B 262 12. .693 34. .658 59. .166 1. .00 0. .00 XXXX4818

ATOM 4819 CD1 PHE B 262 13. .289 35. .609 58. .355 1. .00 0. .00 XXXX4819

ATOM 4820 CD2 PHE B 262 13. .506 33. .826 59. .921 1. .00 0. .00 XXXX4820

ATOM 4821 CE1 PHE B 262 14. .666 35. .739 58. .308 1. .00 0. .00 XXXX4821

ATOM 4822 CE2 PHE B 262 14. .885 33. .950 59. .877 1. .00 0. .00 XXXX4822

ATOM 4823 CZ PHE B 262 15. .466 34. .907 59. .069 1. .00 0. .00 XXXX4823

ATOM 4824 N GLN B 263 8. .244 35. .372 58. .353 1. .00 0. .00 XXXX4824

ATOM 4825 CA GLN B 263 6. .840 34. .990 58. .406 1. .00 0. .00 XXXX4825

ATOM 4826 C GLN B 263 6. .675 33. .690 59. .191 1. .00 0. .00 XXXX4826

ATOM 4827 O GLN B 263 5. .642 33. .454 59. .817 1. .00 0. .00 XXXX4827

ATOM 4828 CB GLN B 263 6. .263 34. .840 56. .996 1. .00 0. .00 XXXX4828

ATOM 4829 CG GLN B 263 4. .827 34. .344 56. .971 1. .00 0. .00 XXXX4829

ATOM 4830 CD GLN B 263 4. .297 34. .148 55. .563 1. .00 0. .00 XXXX4830

ATOM 4831 OE1 GLN B 263 4. .735 34. .811 54. .622 1. .00 0. .00 XXXX4831

ATOM 4832 NE2 GLN B 263 3. .347 33. .231 55. .412 1. .00 0. .00 XXXX4832

ATOM 4833 N SER B 264 7. .710 32. .857 59. .159 1. .00 0. .00 XXXX4833

ATOM 4834 CA SER B 264 7. .665 31. .537 59. .781 1. .00 0. .00 XXXX4834

ATOM 4835 C SER B 264 7. .914 31. .569 61. .290 1. .00 0. .00 XXXX4835

ATOM 4836 O SER B 264 7. .927 30. .524 61. .939 1. .00 0. .00 XXXX4836

ATOM 4837 CB SER B 264 8. .685 30. .612 59. .115 1. .00 0. .00 XXXX4837

ATOM 4838 OG SER B 264 9. .993 31. .148 59. .214 1. .00 0. .00 XXXX4838

ATOM 4839 N VAL B 265 8. .114 32. .760 61. .847 1. .00 0. .00 XXXX4839

ATOM 4840 CA VAL B 265 8. .380 32. .887 63. .278 1. .00 0. .00 XXXX4840

ATOM 4841 C VAL B 265 7. .211 32. .370 64. .109 1. .00 0. .00 XXXX4841

ATOM 4842 O VAL B 265 6. .062 32. .752 63. .888 1. .00 0. .00 XXXX4842

ATOM 4843 CB VAL B 265 8. .670 34. .343 63. .677 1. .00 0. .00 XXXX4843

ATOM 4844 CGI VAL B 265 8. .514 34. .522 65. .184 1. .00 0. .00 XXXX4844

ATOM 4845 CG2 VAL B 265 10. .064 34. .750 63. .219 1. .00 0. .00 XXXX4845

ATOM 4846 N ASP B 266 7. .515 31. .502 65. .069 1. .00 0. .00 XXXX4846

ATOM 4847 CA ASP B 266 6. .483 30. .851 65. .867 1. .00 0. .00 XXXX4847

ATOM 4848 C ASP B 266 6. .220 31. .578 67. .181 1. .00 0. .00 XXXX4848

ATOM 4849 O ASP B 266 6. .785 31. .237 68. .219 1. .00 0. .00 XXXX4849

ATOM 4850 CB ASP B 266 6. .866 29. .397 66. .148 1. .00 0. .00 XXXX4850

ATOM 4851 CG ASP B 266 5. .786 28. .646 66. .903 1. .00 0. .00 XXXX4851

ATOM 4852 OD1 ASP B 266 4. .601 29. .018 66. .777 1. .00 0. .00 XXXX4852

ATOM 4853 OD2 ASP B 266 6. .123 27. .682 67. .623 1. .00 0. .00 XXXX4853

ATOM 4854 N THR B 267 5. .360 32. .587 67. .124 1. .00 0. .00 XXXX4854

ATOM 4855 CA THR B 267 4. .855 33. .233 68. .325 1. .00 0. .00 XXXX4855

ATOM 4856 C THR B 267 3. .348 33. .363 68. .185 1. .00 0. .00 XXXX4856

ATOM 4857 O THR B 267 2. .832 33. .374 67. .067 1. .00 0. .00 XXXX4857

ATOM 4858 CB THR B 267 5. .477 34. .625 68. .551 1. .00 0. .00 XXXX4858

ATOM 4859 OG1 THR B 267 5. .138 35. .488 67. .459 1. .00 0. .00 XXXX4859

ATOM 4860 CG2 THR B 267 6. .992 34. .528 68. .670 1. .00 0. .00 XXXX4860

ATOM 4861 N PRO B 268 2. .634 33. .452 69. .315 1. .00 0. .00 XXXX4861

ATOM 4862 CA PRO B 268 1. .191 33. .702 69. .258 1. .00 0. .00 XXXX4862

ATOM 4863 C PRO B 268 0. .912 35. .013 68. .534 1. .00 0. .00 XXXX4863

ATOM 4864 O PRO B 268 -0. .020 35. .102 67. .735 1. .00 0. .00 XXXX4864

ATOM 4865 CB PRO B 268 0. .782 33. .778 70. .733 1. .00 0. .00 XXXX4865

ATOM 4866 CG PRO B 268 1. .852 33. .032 71. .464 1. .00 0. .00 XXXX4866

ATOM 4867 CD PRO B 268 3. .116 33. .289 70. .697 1. .00 0. .00 XXXX4867 Attorney Docket No. 35327-522001 WO

ATOM 4868 N GLU B 269 1. .735 36. .018 68. .818 1. .00 0. .00 XXXX4868

ATOM 4869 CA GLU B 269 1. .617 37. .324 68. .182 1. .00 0. .00 XXXX4869

ATOM 4870 C GLU B 269 1. .746 37. .231 66. .662 1. .00 0. .00 XXXX4870

ATOM 4871 O GLU B 269 0. .972 37. .848 65. .930 1. .00 0. .00 XXXX4871

ATOM 4872 CB GLU B 269 2. .671 38. .283 68. .740 1. .00 0. .00 XXXX4872

ATOM 4873 CG GLU B 269 2. .317 38. .867 70. .101 1. .00 0. .00 XXXX4873

ATOM 4874 CD GLU B 269 2. .566 37. .897 71. .241 1. .00 0. .00 XXXX4874

ATOM 4875 OE1 GLU B 269 3. .296 36. .905 71. .033 1. .00 0. .00 XXXX4875

ATOM 4876 OE2 GLU B 269 2. .031 38. .128 72. .347 1. .00 0. .00 XXXX4876

ATOM 4877 N ASN B 270 2. .723 36. .463 66. .187 1. .00 0. .00 XXXX4877

ATOM 4878 CA ASN B 270 2. .946 36. .347 64. .750 1. .00 0. .00 XXXX4878

ATOM 4879 C ASN B 270 1. .835 35. .564 64. .060 1. .00 0. .00 XXXX4879

ATOM 4880 O ASN B 270 1. .460 35. .877 62. .932 1. .00 0. .00 XXXX4880

ATOM 4881 CB ASN B 270 4. .294 35. .690 64. .458 1. .00 0. .00 XXXX4881

ATOM 4882 CG ASN B 270 4. .679 35. .793 62. .994 1. .00 0. .00 XXXX4882

ATOM 4883 OD1 ASN B 270 4. .361 36. .779 62. .328 1. .00 0. .00 XXXX4883

ATOM 4884 ND2 ASN B 270 5. .361 34. .773 62. .485 1. .00 0. .00 XXXX4884

ATOM 4885 N LYS B 271 1. .321 34. .543 64. .739 1. .00 0. .00 XXXX4885

ATOM 4886 CA LYS B 271 0. .199 33. .768 64. .222 1. .00 0. .00 XXXX4886

ATOM 4887 C LYS B 271 -0. .983 34. .678 63. .905 1. .00 0. .00 XXXX4887

ATOM 4888 O LYS B 271 -1. .582 34. .587 62. .833 1. .00 0. .00 XXXX4888

ATOM 4889 CB LYS B 271 -0. .216 32. .688 65. .225 1. .00 0. .00 XXXX4889

ATOM 4890 CG LYS B 271 -1. .345 31. .785 64. .743 1. .00 0. .00 XXXX4890

ATOM 4891 CD LYS B 271 -1. .667 30. .703 65. .764 1. .00 0. .00 XXXX4891

ATOM 4892 CE LYS B 271 -2. .936 29. .946 65. .396 1. .00 0. .00 XXXX4892

ATOM 4893 NZ LYS B 271 -2. .805 29. .221 64. .101 1. .00 0. .00 XXXX4893

ATOM 4894 N GLU B 272 -1. .309 35. .554 64. .851 1. .00 0. .00 XXXX4894

ATOM 4895 CA GLU B 272 -2. .384 36. .524 64. .677 1. .00 0. .00 XXXX4895

ATOM 4896 C GLU B 272 -2. .082 37. .516 63. .559 1. .00 0. .00 XXXX4896

ATOM 4897 O GLU B 272 -2. .948 37. .830 62. .743 1. .00 0. .00 XXXX4897

ATOM 4898 CB GLU B 272 -2. .641 37. .274 65. .987 1. .00 0. .00 XXXX4898

ATOM 4899 CG GLU B 272 -3. .265 36. .419 67. .076 1. .00 0. .00 XXXX4899

ATOM 4900 CD GLU B 272 -4. .590 35. .818 66. .650 1. .00 0. .00 XXXX4900

ATOM 4901 OE1 GLU B 272 -5. .351 36. .504 65. .935 1. .00 0. .00 XXXX4901

ATOM 4902 OE2 GLU B 272 -4. .869 34. .660 67. .026 1. .00 0. .00 XXXX4902

ATOM 4903 N PHE B 273 -0. .847 38. .006 63. .530 1. .00 0. .00 XXXX4903

ATOM 4904 CA PHE B 273 -0. .436 39. .009 62. .553 1. .00 0. .00 XXXX4904

ATOM 4905 C PHE B 273 -0. .534 38. .491 61. .120 1. .00 0. .00 XXXX4905

ATOM 4906 O PHE B 273 -1. .106 39. .151 60. .251 1. .00 0. .00 XXXX4906

ATOM 4907 CB PHE B 273 0. .993 39. .471 62. .848 1. .00 0. .00 XXXX4907

ATOM 4908 CG PHE B 273 1. .536 40. .448 61. .845 1. .00 0. .00 XXXX4908

ATOM 4909 CD1 PHE B 273 0. .898 41. .655 61. .616 1. .00 0. .00 XXXX4909

ATOM 4910 CD2 PHE B 273 2. .694 40. .163 61. .140 1. .00 0. .00 XXXX4910

ATOM 4911 CE1 PHE B 273 1. .398 42. .556 60. .696 1. .00 0. .00 XXXX4911

ATOM 4912 CE2 PHE B 273 3. .201 41. .061 60. .220 1. .00 0. .00 XXXX4912

ATOM 4913 CZ PHE B 273 2. .552 42. .259 59. .998 1. .00 0. .00 XXXX4913

ATOM 4914 N VAL B 274 0. .023 37. .309 60. .879 1. .00 0. .00 XXXX4914

ATOM 4915 CA VAL B 274 0. .000 36. .708 59. .550 1. .00 0. .00 XXXX4915

ATOM 4916 C VAL B 274 -1. .428 36. .376 59. .126 1. .00 0. .00 XXXX4916

ATOM 4917 O VAL B 274 -1. .801 36. .568 57. .968 1. .00 0. .00 XXXX4917

ATOM 4918 CB VAL B 274 0. .863 35. .435 59. .485 1. .00 0. .00 XXXX4918

ATOM 4919 CGI VAL B 274 0. .703 34. .756 58. .134 1. .00 0. .00 XXXX4919

ATOM 4920 CG2 VAL B 274 2. .325 35. .772 59. .747 1. .00 0. .00 XXXX4920

ATOM 4921 N GLU B 275 -2. .221 35. .866 60. .065 1. .00 0. .00 XXXX4921

ATOM 4922 CA GLU B 275 -3. .624 35. .573 59. .796 1. .00 0. .00 XXXX4922

ATOM 4923 C GLU B 275 -4. .378 36. .831 59. .375 1. .00 0. .00 XXXX4923

ATOM 4924 O GLU B 275 -5. .126 36. .815 58. .396 1. .00 0. .00 XXXX4924

ATOM 4925 CB GLU B 275 -4. .297 34. .949 61. .021 1. .00 0. .00 XXXX4925

ATOM 4926 CG GLU B 275 -4. .027 33. .462 61. .203 1. .00 0. .00 XXXX4926

ATOM 4927 CD GLU B 275 -4. .905 32. .839 62. .274 1. .00 0. .00 XXXX4927

ATOM 4928 OE1 GLU B 275 -5. .968 33. .418 62. .583 1. .00 0. .00 XXXX4928

ATOM 4929 OE2 GLU B 275 -4. .534 31. .771 62. .805 1. .00 0. .00 XXXX4929

ATOM 4930 N LYS B 276 -4. .179 37. .918 60. .116 1. .00 0. .00 XXXX4930

ATOM 4931 CA LYS B 276 -4. .855 39. .180 59. .819 1. .00 0. .00 XXXX4931

ATOM 4932 C LYS B 276 -4. .406 39. .790 58. .492 1. .00 0. .00 XXXX4932

ATOM 4933 O LYS B 276 -5. .228 40. .294 57. .726 1. .00 0. .00 XXXX4933

ATOM 4934 CB LYS B 276 -4. .632 40. .188 60. .950 1. .00 0. .00 XXXX4934 Attorney Docket No. 35327-522001 WO

ATOM 4935 CG LYS B 276 -5. .471 39. .923 62. .189 1. .00 0. .00 XXXX4935

ATOM 4936 CD LYS B 276 -5. .379 41. .075 63. .178 1. .00 0. .00 XXXX4936

ATOM 4937 CE LYS B 276 -3. .988 41. .193 63. .774 1. .00 0. .00 XXXX4937

ATOM 4938 NZ LYS B 276 -3. .928 42. .245 64. .826 1. .00 0. .00 XXXX4938

ATOM 4939 N TYR B 277 -3. .103 39. .749 58. .229 1. .00 0. .00 XXXX4939

ATOM 4940 CA TYR B 277 -2. .556 40. .286 56. .986 1. .00 0. .00 XXXX4940

ATOM 4941 C TYR B 277 -3. .138 39. .534 55. .790 1. .00 0. .00 XXXX4941

ATOM 4942 O TYR B 277 -3. .502 40. .138 54. .780 1. .00 0. .00 XXXX4942

ATOM 4943 CB TYR B 277 -1. .026 40. .197 56. .991 1. .00 0. .00 XXXX4943

ATOM 4944 CG TYR B 277 -0. .336 41. .056 55. .949 1. .00 0. .00 XXXX4944

ATOM 4945 CD1 TYR B 277 0. .089 40. .516 54. .741 1. .00 0. .00 XXXX4945

ATOM 4946 CD2 TYR B 277 -0. .096 42. .404 56. .182 1. .00 0. .00 XXXX4946

ATOM 4947 CE1 TYR B 277 0. .727 41. .297 53. .791 1. .00 0. .00 XXXX4947

ATOM 4948 CE2 TYR B 277 0. .540 43. .193 55. .240 1. .00 0. .00 XXXX4948

ATOM 4949 CZ TYR B 277 0. .950 42. .636 54. .047 1. .00 0. .00 XXXX4949

ATOM 4950 OH TYR B 277 1. .583 43. .422 53. .111 1. .00 0. .00 XXXX4950

ATOM 4951 N LYS B 278 -3. .229 38. .214 55. .916 1. .00 0. .00 XXXX4951

ATOM 4952 CA LYS B 278 -3. .764 37. .374 54. .850 1. .00 0. .00 XXXX4952

ATOM 4953 C LYS B 278 -5. .276 37. .535 54. .706 1. .00 0. .00 XXXX4953

ATOM 4954 O LYS B 278 -5. .806 37. .522 53. .594 1. .00 0. .00 XXXX4954

ATOM 4955 CB LYS B 278 -3. .417 35. .905 55. .099 1. .00 0. .00 XXXX4955

ATOM 4956 CG LYS B 278 -1. .955 35. .559 54. .855 1. .00 0. .00 XXXX4956

ATOM 4957 CD LYS B 278 -1. .670 34. .106 55. .202 1. .00 0. .00 XXXX4957

ATOM 4958 CE LYS B 278 -0. .232 33. .730 54. .890 1. .00 0. .00 XXXX4958

ATOM 4959 NZ LYS B 278 0. .027 33. .708 53. .423 1. .00 0. .00 XXXX4959

ATOM 4960 N LYS B 279 -5. .967 37. .683 55. .832 1. .00 0. .00 XXXX4960

ATOM 4961 CA LYS B 279 -7. .410 37. .899 55. .809 1. .00 0. .00 XXXX4961

ATOM 4962 C LYS B 279 -7. .761 39. .182 55. .059 1. .00 0. .00 XXXX4962

ATOM 4963 O LYS B 279 -8. .744 39. .230 54. .319 1. .00 0. .00 XXXX4963

ATOM 4964 CB LYS B 279 -7. .974 37. .949 57. .231 1. .00 0. .00 XXXX4964

ATOM 4965 CG LYS B 279 -9. .471 38. .218 57. .284 1. .00 0. .00 XXXX4965

ATOM 4966 CD LYS B 279 -9. .997 38. .220 58. .712 1. .00 0. .00 XXXX4966

ATOM 4967 CE LYS B 279 -11. .476 38. .583 58. .753 1. .00 0. .00 XXXX4967

ATOM 4968 NZ LYS B 279 -12. .039 38. .486 60. .129 1. .00 0. .00 XXXX4968

ATOM 4969 N LYS B 280 -6. .955 40. .220 55. .251 1. .00 0. .00 XXXX4969

ATOM 4970 CA LYS B 280 -7. .212 41. .504 54. .608 1. .00 0. .00 XXXX4970

ATOM 4971 C LYS B 280 -6. .781 41. .535 53. .143 1. .00 0. .00 XXXX4971

ATOM 4972 O LYS B 280 -7. .499 42. .062 52. .294 1. .00 0. .00 XXXX4972

ATOM 4973 CB LYS B 280 -6. .516 42. .636 55. .367 1. .00 0. .00 XXXX4973

ATOM 4974 CG LYS B 280 -6. .863 44. .017 54. .827 1. .00 0. .00 XXXX4974

ATOM 4975 CD LYS B 280 -6. .317 45. .129 55. .702 1. .00 0. .00 XXXX4975

ATOM 4976 CE LYS B 280 -6. .678 46. .495 55. .134 1. .00 0. .00 XXXX4976

ATOM 4977 NZ LYS B 280 -8. .145 46. .635 54. .908 1. .00 0. .00 XXXX4977

ATOM 4978 N TYR B 281 -5. .612 40. .976 52. .846 1. .00 0. .00 XXXX4978

ATOM 4979 CA TYR B 281 -5. .025 41. .132 51. .518 1. .00 0. .00 XXXX4979

ATOM 4980 C TYR B 281 -4. .997 39. .852 50. .680 1. .00 0. .00 XXXX4980

ATOM 4981 O TYR B 281 -4. .686 39. .900 49. .491 1. .00 0. .00 XXXX4981

ATOM 4982 CB TYR B 281 -3. .606 41. .693 51. .643 1. .00 0. .00 XXXX4982

ATOM 4983 CG TYR B 281 -3. .566 43. .083 52. .237 1. .00 0. .00 XXXX4983

ATOM 4984 CD1 TYR B 281 -4. .176 44. .150 51. .590 1. .00 0. .00 XXXX4984

ATOM 4985 CD2 TYR B 281 -2. .927 43. .329 53. .446 1. .00 0. .00 XXXX4985

ATOM 4986 CE1 TYR B 281 -4. .149 45. .422 52. .125 1. .00 0. .00 XXXX4986

ATOM 4987 CE2 TYR B 281 -2. .894 44. .601 53. .990 1. .00 0. .00 XXXX4987

ATOM 4988 CZ TYR B 281 -3. .508 45. .643 53. .324 1. .00 0. .00 XXXX4988

ATOM 4989 OH TYR B 281 -3. .481 46. .912 53. .855 1. .00 0. .00 XXXX4989

ATOM 4990 N GLY B 282 -5. .314 38. .712 51. .286 1. .00 0. .00 XXXX4990

ATOM 4991 CA GLY B 282 -5. .362 37. .467 50. .538 1. .00 0. .00 XXXX4991

ATOM 4992 C GLY B 282 -4. .461 36. .373 51. .083 1. .00 0. .00 XXXX4992

ATOM 4993 O GLY B 282 -3. .369 36. .644 51. .581 1. .00 0. .00 XXXX4993

ATOM 4994 N GLU B 283 -4. .922 35. .131 50. .982 1. .00 0. .00 XXXX4994

ATOM 4995 CA GLU B 283 -4. .202 33. .990 51. .539 1. .00 0. .00 XXXX4995

ATOM 4996 C GLU B 283 -2. .855 33. .733 50. .863 1. .00 0. .00 XXXX4996

ATOM 4997 O GLU B 283 -2. .007 33. .025 51. .407 1. .00 0. .00 XXXX4997

ATOM 4998 CB GLU B 283 -5. .070 32. .734 51. .450 1. .00 0. .00 XXXX4998

ATOM 4999 CG GLU B 283 -6. .161 32. .659 52. .507 1. .00 0. .00 XXXX4999

ATOM 5000 CD GLU B 283 -5. .611 32. .692 53. .923 1. .00 0. .00 XXXX5000

ATOM 5001 OE1 GLU B 283 -4. .630 31. .971 54. .199 1. .00 0. .00 XXXX5001 Attorney Docket No. 35327-522001 WO

ATOM 5002 OE2 GLU B 283 -6. .162 33. .436 54. .763 1. .00 0. .00 XXXX5002

ATOM 5003 N ASP B 284 -2. .666 34. .307 49. .679 1. .00 0. .00 XXXX5003

ATOM 5004 CA ASP B 284 -1. .422 34. .140 48. .938 1. .00 0. .00 XXXX5004

ATOM 5005 C ASP B 284 -0. .352 35. .139 49. .382 1. .00 0. .00 XXXX5005

ATOM 5006 O ASP B 284 0. .837 34. .941 49. .127 1. .00 0. .00 XXXX5006

ATOM 5007 CB ASP B 284 -1. .676 34. .270 47. .429 1. .00 0. .00 XXXX5007

ATOM 5008 CG ASP B 284 -2. .114 32. .956 46. .796 1. .00 0. .00 XXXX5008

ATOM 5009 OD1 ASP B 284 -2. .455 32. .017 47. .549 1. .00 0. .00 XXXX5009

ATOM 5010 OD2 ASP B 284 -2. .105 32. .860 45. .551 1. .00 0. .00 XXXX5010

ATOM 5011 N ARG B 285 -0. .780 36. .202 50. .055 1. .00 0. .00 XXXX5011

ATOM 5012 CA ARG B 285 0. .130 37. .264 50. .477 1. .00 0. .00 XXXX5012

ATOM 5013 C ARG B 285 1. .057 36. .805 51. .599 1. .00 0. .00 XXXX5013

ATOM 5014 O ARG B 285 0. .658 36. .038 52. .475 1. .00 0. .00 XXXX5014

ATOM 5015 CB ARG B 285 -0. .660 38. .496 50. .926 1. .00 0. .00 XXXX5015

ATOM 5016 CG ARG B 285 -1. .437 39. .190 49. .816 1. .00 0. .00 XXXX5016

ATOM 5017 CD ARG B 285 -0. .511 39. .914 48. .845 1. .00 0. .00 XXXX5017

ATOM 5018 NE ARG B 285 0. .232 40. .999 49. .484 1. .00 0. .00 XXXX5018

ATOM 5019 CZ ARG B 285 -0. .186 42. .261 49. .547 1. .00 0. .00 XXXX5019

ATOM 5020 NH1 ARG B 285 -1. .352 42. .606 49. .018 1. .00 0. .00 XXXX5020

ATOM 5021 NH2 ARG B 285 0. .561 43. .179 50. .148 1. .00 0. .00 XXXX5021

ATOM 5022 N VAL B 286 2. .299 37. .278 51. .565 1. .00 0. .00 XXXX5022

ATOM 5023 CA VAL B 286 3. .275 36. .946 52. .596 1. .00 0. .00 XXXX5023

ATOM 5024 C VAL B 286 3. .578 38. .139 53. .490 1. .00 0. .00 XXXX5024

ATOM 5025 O VAL B 286 3. .252 39. .278 53. .157 1. .00 0. .00 XXXX5025

ATOM 5026 CB VAL B 286 4. .598 36. .448 51. .986 1. .00 0. .00 XXXX5026

ATOM 5027 CGI VAL B 286 4. .367 35. .180 51. .183 1. .00 0. .00 XXXX5027

ATOM 5028 CG2 VAL B 286 5. .227 37. .534 51. .122 1. .00 0. .00 XXXX5028

ATOM 5029 N THR B 287 4. .197 37. .867 54. .634 1. .00 0. .00 XXXX5029

ATOM 5030 CA THR B 287 4. .745 38. .923 55. .470 1. .00 0. .00 XXXX5030

ATOM 5031 C THR B 287 6. .259 38. .768 55. .528 1. .00 0. .00 XXXX5031

ATOM 5032 O THR B 287 6. .792 37. .702 55. .222 1. .00 0. .00 XXXX5032

ATOM 5033 CB THR B 287 4. .175 38. .895 56. .900 1. .00 0. .00 XXXX5033

ATOM 5034 OG1 THR B 287 4. .545 37. .670 57. .545 1. .00 0. .00 XXXX5034

ATOM 5035 CG2 THR B 287 2. .656 39. .025 56. .879 1. .00 0. .00 XXXX5035

ATOM 5036 N ASP B 288 6. .948 39. .833 55. .922 1. .00 0. .00 XXXX5036

ATOM 5037 CA ASP B 288 8. .387 39. .774 56. .140 1. .00 0. .00 XXXX5037

ATOM 5038 C ASP B 288 8. .830 40. .892 57. .078 1. .00 0. .00 XXXX5038

ATOM 5039 O ASP B 288 7. .999 41. .633 57. .603 1. .00 0. .00 XXXX5039

ATOM 5040 CB ASP B 288 9. .152 39. .825 54. .807 1. .00 0. .00 XXXX5040

ATOM 5041 CG ASP B 288 8. .927 41. .116 54. .029 1. .00 0. .00 XXXX5041

ATOM 5042 OD1 ASP B 288 8. .453 42. .115 54. .605 1. .00 0. .00 XXXX5042

ATOM 5043 OD2 ASP B 288 9. .242 41. .129 52. .819 1. .00 0. .00 XXXX5043

ATOM 5044 N ASP B 289 10. .137 41. .003 57. .286 1. .00 0. .00 XXXX5044

ATOM 5045 CA ASP B 289 10. .684 41. .906 58. .295 1. .00 0. .00 XXXX5045

ATOM 5046 C ASP B 289 10. .245 43. .355 58. .067 1. .00 0. .00 XXXX5046

ATOM 5047 O ASP B 289 9. .675 43. .975 58. .966 1. .00 0. .00 XXXX5047

ATOM 5048 CB ASP B 289 12. .215 41. .799 58. .313 1. .00 0. .00 XXXX5048

ATOM 5049 CG ASP B 289 12. .862 42. .702 59. .351 1. .00 0. .00 XXXX5049

ATOM 5050 OD1 ASP B 289 13. .539 42. .169 60. .254 1. .00 0. .00 XXXX5050

ATOM 5051 OD2 ASP B 289 12. .719 43. .937 59. .256 1. .00 0. .00 XXXX5051

ATOM 5052 N PRO B 290 10. .501 43. .897 56. .865 1. .00 0. .00 XXXX5052

ATOM 5053 CA PRO B 290 10. .092 45. .272 56. .554 1. .00 0. .00 XXXX5053

ATOM 5054 C PRO B 290 8. .593 45. .492 56. .738 1. .00 0. .00 XXXX5054

ATOM 5055 O PRO B 290 8. .177 46. .540 57. .231 1. .00 0. .00 XXXX5055

ATOM 5056 CB PRO B 290 10. .488 45. .429 55. .084 1. .00 0. .00 XXXX5056

ATOM 5057 CG PRO B 290 11. .617 44. .474 54. .903 1. .00 0. .00 XXXX5057

ATOM 5058 CD PRO B 290 11. .277 43. .294 55. .766 1. .00 0. .00 XXXX5058

ATOM 5059 N ILE B 291 7. .796 44. .504 56. .346 1. .00 0. .00 XXXX5059

ATOM 5060 CA ILE B 291 6. .351 44. .575 56. .522 1. .00 0. .00 XXXX5060

ATOM 5061 C ILE B 291 5. .976 44. .645 58. .004 1. .00 0. .00 XXXX5061

ATOM 5062 O ILE B 291 5. .087 45. .405 58. .389 1. .00 0. .00 XXXX5062

ATOM 5063 CB ILE B 291 5. .649 43. .376 55. .868 1. .00 0. .00 XXXX5063

ATOM 5064 CGI ILE B 291 5. .678 43. .516 54. .343 1. .00 0. .00 XXXX5064

ATOM 5065 CG2 ILE B 291 4. .218 43. .258 56. .367 1. .00 0. .00 XXXX5065

ATOM 5066 CD1 ILE B 291 5. .241 42. .268 53. .607 1. .00 0. .00 XXXX5066

ATOM 5067 N GLU B 292 6. .653 43. .855 58. .832 1. .00 0. .00 XXXX5067

ATOM 5068 CA GLU B 292 6. .410 43. .895 60. .271 1. .00 0. .00 XXXX5068 Attorney Docket No. 35327-522001 WO

ATOM 5069 C GLU B 292 6. .814 45. .245 60. .851 1. .00 0. .00 XXXX5069

ATOM 5070 O GLU B 292 6. .115 45. .803 61. .697 1. .00 0. .00 XXXX5070

ATOM 5071 CB GLU B 292 7. .164 42. .779 60. .997 1. .00 0. .00 XXXX5071

ATOM 5072 CG GLU B 292 6. .779 42. .670 62. .467 1. .00 0. .00 XXXX5072

ATOM 5073 CD GLU B 292 7. .937 42. .270 63. .361 1. .00 0. .00 XXXX5073

ATOM 5074 OE1 GLU B 292 7. .680 41. .863 64. .513 1. .00 0. .00 XXXX5074

ATOM 5075 OE2 GLU B 292 9. .102 42. .380 62. .922 1. .00 0. .00 XXXX5075

ATOM 5076 N ALA B 293 7. .956 45. .758 60. .400 1. .00 0. .00 XXXX5076

ATOM 5077 CA ALA B 293 8. .486 47. .017 60. .910 1. .00 0. .00 XXXX5077

ATOM 5078 C ALA B 293 7. .555 48. .182 60. .597 1. .00 0. .00 XXXX5078

ATOM 5079 O ALA B 293 7. .359 49. .069 61. .427 1. .00 0. .00 XXXX5079

ATOM 5080 CB ALA B 293 9. .870 47. .278 60. .337 1. .00 0. .00 XXXX5080

ATOM 5081 N ALA B 294 6. .983 48. .174 59. .397 1. .00 0. .00 XXXX5081

ATOM 5082 CA ALA B 294 6. .046 49. .215 58. .992 1. .00 0. .00 XXXX5082

ATOM 5083 C ALA B 294 4. .790 49. .155 59. .852 1. .00 0. .00 XXXX5083

ATOM 5084 O ALA B 294 4. .286 50. .179 60. .312 1. .00 0. .00 XXXX5084

ATOM 5085 CB ALA B 294 5. .691 49. .072 57. .523 1. .00 0. .00 XXXX5085

ATOM 5086 N TYR B 295 4. .295 47. .939 60. .059 1. .00 0. .00 XXXX5086

ATOM 5087 CA TYR B 295 3. .128 47. .694 60. .898 1. .00 0. .00 XXXX5087

ATOM 5088 C TYR B 295 3. .402 48. .116 62. .339 1. .00 0. .00 XXXX5088

ATOM 5089 O TYR B 295 2. .611 48. .837 62. .949 1. .00 0. .00 XXXX5089

ATOM 5090 CB TYR B 295 2. .744 46. .215 60. .833 1. .00 0. .00 XXXX5090

ATOM 5091 CG TYR B 295 1. .605 45. .802 61. .741 1. .00 0. .00 XXXX5091

ATOM 5092 CD1 TYR B 295 1. .854 45. .222 62. .977 1. .00 0. .00 XXXX5092

ATOM 5093 CD2 TYR B 295 0. .282 45. .977 61. .354 1. .00 0. .00 XXXX5093

ATOM 5094 CE1 TYR B 295 0. .821 44. .833 63. .806 1. .00 0. .00 XXXX5094

ATOM 5095 CE2 TYR B 295 -0. .760 45. .591 62. .176 1. .00 0. .00 XXXX5095

ATOM 5096 CZ TYR B 295 -0. .484 45. .019 63. .402 1. .00 0. .00 XXXX5096

ATOM 5097 OH TYR B 295 -1. .516 44. .633 64. .226 1. .00 0. .00 XXXX5097

ATOM 5098 N ILE B 296 4. .526 47. .646 62. .873 1. .00 0. .00 XXXX5098

ATOM 5099 CA ILE B 296 4. .981 48. .012 64. .210 1. .00 0. .00 XXXX5099

ATOM 5100 C ILE B 296 5. .103 49. .523 64. .389 1. .00 0. .00 XXXX5100

ATOM 5101 O ILE B 296 4. .692 50. .072 65. .413 1. .00 0. .00 XXXX5101

ATOM 5102 CB ILE B 296 6. .348 47. .370 64. .525 1. .00 0. .00 XXXX5102

ATOM 5103 CGI ILE B 296 6. .179 45. .893 64. .885 1. .00 0. .00 XXXX5103

ATOM 5104 CG2 ILE B 296 7. .053 48. .128 65. .642 1. .00 0. .00 XXXX5104

ATOM 5105 CD1 ILE B 296 7. .484 45. .201 65. .203 1. .00 0. .00 XXXX5105

ATOM 5106 N GLY B 297 5. .675 50. .186 63. .389 1. .00 0. .00 XXXX5106

ATOM 5107 CA GLY B 297 5. .912 51. .617 63. .446 1. .00 0. .00 XXXX5107

ATOM 5108 C GLY B 297 4. .657 52. .430 63. .701 1. .00 0. .00 XXXX5108

ATOM 5109 O GLY B 297 4. .677 53. .384 64. .476 1. .00 0. .00 XXXX5109

ATOM 5110 N VAL B 298 3. .563 52. .055 63. .046 1. .00 0. .00 XXXX5110

ATOM 5111 CA VAL B 298 2. .292 52. .747 63. .230 1. .00 0. .00 XXXX5111

ATOM 5112 C VAL B 298 1. .792 52. .613 64. .667 1. .00 0. .00 XXXX5112

ATOM 5113 O VAL B 298 1. .358 53. .591 65. .276 1. .00 0. .00 XXXX5113

ATOM 5114 CB VAL B 298 1. .214 52. .215 62. .268 1. .00 0. .00 XXXX5114

ATOM 5115 CGI VAL B 298 -0. .133 52. .854 62. .574 1. .00 0. .00 XXXX5115

ATOM 5116 CG2 VAL B 298 1. .620 52. .471 60. .822 1. .00 0. .00 XXXX5116

ATOM 5117 N TYR B 299 1. .857 51. .399 65. .203 1. .00 0. .00 XXXX5117

ATOM 5118 CA TYR B 299 1. .417 51. .146 66. .569 1. .00 0. .00 XXXX5118

ATOM 5119 C TYR B 299 2. .276 51. .877 67. .596 1. .00 0. .00 XXXX5119

ATOM 5120 O TYR B 299 1. .761 52. .392 68. .586 1. .00 0. .00 XXXX5120

ATOM 5121 CB TYR B 299 1. .410 49. .644 66. .864 1. .00 0. .00 XXXX5121

ATOM 5122 CG TYR B 299 0. .078 48. .994 66. .575 1. .00 0. .00 XXXX5122

ATOM 5123 CD1 TYR B 299 -0. .154 48. .340 65. .373 1. .00 0. .00 XXXX5123

ATOM 5124 CD2 TYR B 299 -0. .957 49. .053 67. .500 1. .00 0. .00 XXXX5124

ATOM 5125 CE1 TYR B 299 -1. .378 47. .752 65. .106 1. .00 0. .00 XXXX5125

ATOM 5126 CE2 TYR B 299 -2. .182 48. .468 67. .242 1. .00 0. .00 XXXX5126

ATOM 5127 CZ TYR B 299 -2. .388 47. .820 66. .043 1. .00 0. .00 XXXX5127

ATOM 5128 OH TYR B 299 -3. .608 47. .237 65. .780 1. .00 0. .00 XXXX5128

ATOM 5129 N LEU B 300 3. .583 51. .923 67. .359 1. .00 0. .00 XXXX5129

ATOM 5130 CA LEU B 300 4. .488 52. .569 68. .303 1. .00 0. .00 XXXX5130

ATOM 5131 C LEU B 300 4. .295 54. .084 68. .324 1. .00 0. .00 XXXX5131

ATOM 5132 O LEU B 300 4. .319 54. .699 69. .390 1. .00 0. .00 XXXX5132

ATOM 5133 CB LEU B 300 5. .941 52. .221 67. .980 1. .00 0. .00 XXXX5133

ATOM 5134 CG LEU B 300 6. .383 50. .840 68. .473 1. .00 0. .00 XXXX5134

ATOM 5135 CD1 LEU B 300 7. .773 50. .495 67. .965 1. .00 0. .00 XXXX5135 Attorney Docket No. 35327-522001 WO

ATOM 5136 CD2 LEU B 300 6. .324 50. .761 69. .996 1. .00 0. .00 XXXX5136

ATOM 5137 N TRP B 301 4. .106 54. .687 67. .153 1. .00 0. .00 XXXX5137

ATOM 5138 CA TRP B 301 3. .789 56. .111 67. .088 1. .00 0. .00 XXXX5138

ATOM 5139 C TRP B 301 2. .499 56. .420 67. .836 1. .00 0. .00 XXXX5139

ATOM 5140 O TRP B 301 2. .432 57. .370 68. .618 1. .00 0. .00 XXXX5140

ATOM 5141 CB TRP B 301 3. .663 56. .588 65. .642 1. .00 0. .00 XXXX5141

ATOM 5142 CG TRP B 301 3. .075 57. .967 65. .545 1. .00 0. .00 XXXX5142

ATOM 5143 CD1 TRP B 301 3. .727 59. .151 65. .734 1. .00 0. .00 XXXX5143

ATOM 5144 CD2 TRP B 301 1. .712 58. .302 65. .253 1. .00 0. .00 XXXX5144

ATOM 5145 NE1 TRP B 301 2. .857 60. .202 65. .572 1. .00 0. .00 XXXX5145

ATOM 5146 CE2 TRP B 301 1. .615 59. .708 65. .275 1. .00 0. .00 XXXX5146

ATOM 5147 CE3 TRP B 301 0. .567 57. .551 64. .969 1. .00 0. .00 XXXX5147

ATOM 5148 CZ2 TRP B 301 0. .417 60. .378 65. .026 1. .00 0. .00 XXXX5148

ATOM 5149 CZ3 TRP B 301 -0. .620 58. .219 64. .722 1. .00 0. .00 XXXX5149

ATOM 5150 CH2 TRP B 301 -0. .685 59. .618 64. .750 1. .00 0. .00 XXXX5150

ATOM 5151 N ALA B 302 1. .473 55. .617 67. .580 1. .00 0. .00 XXXX5151

ATOM 5152 CA ALA B 302 0. .167 55. .825 68. .189 1. .00 0. .00 XXXX5152

ATOM 5153 C ALA B 302 0. .247 55. .700 69. .708 1. .00 0. .00 XXXX5153

ATOM 5154 O ALA B 302 -0. .391 56. .461 70. .435 1. .00 0. .00 XXXX5154

ATOM 5155 CB ALA B 302 -0. .845 54. .842 67. .623 1. .00 0. .00 XXXX5155

ATOM 5156 N LYS B 303 1. .037 54. .740 70. .182 1. .00 0. .00 XXXX5156

ATOM 5157 CA LYS B 303 1. .243 54. .560 71. .614 1. .00 0. .00 XXXX5157

ATOM 5158 C LYS B 303 1. .957 55. .764 72. .226 1. .00 0. .00 XXXX5158

ATOM 5159 O LYS B 303 1. .640 56. .184 73. .339 1. .00 0. .00 XXXX5159

ATOM 5160 CB LYS B 303 2. .034 53. .278 71. .890 1. .00 0. .00 XXXX5160

ATOM 5161 CG LYS B 303 1. .269 52. .003 71. .569 1. .00 0. .00 XXXX5161

ATOM 5162 CD LYS B 303 2. .013 50. .765 72. .045 1. .00 0. .00 XXXX5162

ATOM 5163 CE LYS B 303 2. .153 50. .763 73. .560 1. .00 0. .00 XXXX5163

ATOM 5164 NZ LYS B 303 2. .666 49. .466 74. .079 1. .00 0. .00 XXXX5164

ATOM 5165 N ALA B 304 2. .925 56. .313 71. .498 1. .00 0. .00 XXXX5165

ATOM 5166 CA ALA B 304 3. .642 57. .497 71. .963 1. .00 0. .00 XXXX5166

ATOM 5167 C ALA B 304 2. .715 58. .707 72. .051 1. .00 0. .00 XXXX5167

ATOM 5168 O ALA B 304 2. .787 59. .490 72. .999 1. .00 0. .00 XXXX5168

ATOM 5169 CB ALA B 304 4. .821 57. .795 71. .050 1. .00 0. .00 XXXX5169

ATOM 5170 N VAL B 305 1. .840 58. .851 71. .060 1. .00 0. .00 XXXX5170

ATOM 5171 CA VAL B 305 0. .865 59. .937 71. .045 1. .00 0. .00 XXXX5171

ATOM 5172 C VAL B 305 -0. .119 59. .795 72. .202 1. .00 0. .00 XXXX5172

ATOM 5173 O VAL B 305 -0. .412 60. .763 72. .907 1. .00 0. .00 XXXX5173

ATOM 5174 CB VAL B 305 0. .085 59. .980 69. .719 1. .00 0. .00 XXXX5174

ATOM 5175 CGI VAL B 305 -1. .115 60. .903 69. .841 1. .00 0. .00 XXXX5175

ATOM 5176 CG2 VAL B 305 0. .995 60. .423 68. .582 1. .00 0. .00 XXXX5176

ATOM 5177 N GLU B 306 -0. .630 58. .580 72. .380 1. .00 0. .00 XXXX5177

ATOM 5178 CA GLU B 306 -1. .529 58. .262 73. .486 1. .00 0. .00 XXXX5178

ATOM 5179 C GLU B 306 -0. .912 58. .605 74. .837 1. .00 0. .00 XXXX5179

ATOM 5180 O GLU B 306 -1. .553 59. .227 75. .686 1. .00 0. .00 XXXX5180

ATOM 5181 CB GLU B 306 -1. .906 56. .779 73. .444 1. .00 0. .00 XXXX5181

ATOM 5182 CG GLU B 306 -3. .029 56. .458 72. .479 1. .00 0. .00 XXXX5182

ATOM 5183 CD GLU B 306 -4. .330 57. .112 72. .888 1. .00 0. .00 XXXX5183

ATOM 5184 OE1 GLU B 306 -4. .583 57. .189 74. .107 1. .00 0. .00 XXXX5184

ATOM 5185 OE2 GLU B 306 -5. .092 57. .552 72. .001 1. .00 0. .00 XXXX5185

ATOM 5186 N LYS B 307 0. .339 58. .198 75. .023 1. .00 0. .00 XXXX5186

ATOM 5187 CA LYS B 307 1. .062 58. .443 76. .263 1. .00 0. .00 XXXX5187

ATOM 5188 C LYS B 307 1. .350 59. .929 76. .454 1. .00 0. .00 XXXX5188

ATOM 5189 O LYS B 307 1. .239 60. .457 77. .561 1. .00 0. .00 XXXX5189

ATOM 5190 CB LYS B 307 2. .365 57. .640 76. .274 1. .00 0. .00 XXXX5190

ATOM 5191 CG LYS B 307 3. .236 57. .843 77. .499 1. .00 0. .00 XXXX5191

ATOM 5192 CD LYS B 307 4. .498 57. .002 77. .390 1. .00 0. .00 XXXX5192

ATOM 5193 CE LYS B 307 5. .546 57. .413 78. .407 1. .00 0. .00 XXXX5193

ATOM 5194 NZ LYS B 307 6. .834 56. .702 78. .171 1. .00 0. .00 XXXX5194

ATOM 5195 N ALA B 308 1. .719 60. .599 75. .367 1. .00 0. .00 XXXX5195

ATOM 5196 CA ALA B 308 2. .017 62. .026 75. .407 1. .00 0. .00 XXXX5196

ATOM 5197 C ALA B 308 0. .754 62. .860 75. .589 1. .00 0. .00 XXXX5197

ATOM 5198 O ALA B 308 0. .809 63. .983 76. .092 1. .00 0. .00 XXXX5198

ATOM 5199 CB ALA B 308 2. .748 62. .449 74. .141 1. .00 0. .00 XXXX5199

ATOM 5200 N GLY B 309 -0. .383 62. .311 75. .173 1. .00 0. .00 XXXX5200

ATOM 5201 CA GLY B 309 -1. .634 63. .045 75. .206 1. .00 0. .00 XXXX5201

ATOM 5202 C GLY B 309 -1. .660 64. .135 74. .151 1. .00 0. .00 XXXX5202 Attorney Docket No. 35327-522001 WO

ATOM 5203 O GLY B 309 -2. .453 65. .073 74. .230 1. .00 0. .00 XXXX5203

ATOM 5204 N SER B 310 -0. .782 64. .008 73. .161 1. .00 0. .00 XXXX5204

ATOM 5205 CA SER B 310 -0. .627 65. .030 72. .133 1. .00 0. .00 XXXX5205

ATOM 5206 C SER B 310 0. .140 64. .489 70. .932 1. .00 0. .00 XXXX5206

ATOM 5207 O SER B 310 0. .955 63. .577 71. .066 1. .00 0. .00 XXXX5207

ATOM 5208 CB SER B 310 0. .091 66. .256 72. .703 1. .00 0. .00 XXXX5208

ATOM 5209 OG SER B 310 0. .316 67. .232 71. .701 1. .00 0. .00 XXXX5209

ATOM 5210 N THR B 311 -0. .125 65. .054 69. .758 1. .00 0. .00 XXXX5210

ATOM 5211 CA THR B 311 0. .622 64. .699 68. .557 1. .00 0. .00 XXXX5211

ATOM 5212 C THR B 311 1. .834 65. .607 68. .383 1. .00 0. .00 XXXX5212

ATOM 5213 O THR B 311 2. .617 65. .434 67. .449 1. .00 0. .00 XXXX5213

ATOM 5214 CB THR B 311 -0. .257 64. .779 67. .294 1. .00 0. .00 XXXX5214

ATOM 5215 OG1 THR B 311 -0. .735 66. .118 67. .124 1. .00 0. .00 XXXX5215

ATOM 5216 CG2 THR B 311 -1. .440 63. .830 67. .406 1. .00 0. .00 XXXX5216

ATOM 5217 N ASP B 312 1. .974 66. .582 69. .278 1. .00 0. .00 XXXX5217

ATOM 5218 CA ASP B 312 3. .128 67. .476 69. .262 1. .00 0. .00 XXXX5218

ATOM 5219 C ASP B 312 4. .415 66. .656 69. .263 1. .00 0. .00 XXXX5219

ATOM 5220 O ASP B 312 4. .613 65. .800 70. .125 1. .00 0. .00 XXXX5220

ATOM 5221 CB ASP B 312 3. .094 68. .430 70. .458 1. .00 0. .00 XXXX5221

ATOM 5222 CG ASP B 312 4. .312 69. .330 70. .518 1. .00 0. .00 XXXX5222

ATOM 5223 OD1 ASP B 312 4. .347 70. .336 69. .776 1. .00 0. .00 XXXX5223

ATOM 5224 OD2 ASP B 312 5. .236 69. .033 71. .305 1. .00 0. .00 XXXX5224

ATOM 5225 N VAL B 313 5. .281 66. .924 68. .291 1. .00 0. .00 XXXX5225

ATOM 5226 CA VAL B 313 6. .447 66. .082 68. .035 1. .00 0. .00 XXXX5226

ATOM 5227 C VAL B 313 7. .392 65. .979 69. .229 1. .00 0. .00 XXXX5227

ATOM 5228 O VAL B 313 7. .876 64. .893 69. .551 1. .00 0. .00 XXXX5228

ATOM 5229 CB VAL B 313 7. .237 66. .593 66. .816 1. .00 0. .00 XXXX5229

ATOM 5230 CGI VAL B 313 8. .619 65. .958 66. .773 1. .00 0. .00 XXXX5230

ATOM 5231 CG2 VAL B 313 6. .471 66. .298 65. .535 1. .00 0. .00 XXXX5231

ATOM 5232 N ASP B 314 7. .651 67. .105 69. .885 1. .00 0. .00 XXXX5232

ATOM 5233 CA ASP B 314 8. .546 67. .116 71. .037 1. .00 0. .00 XXXX5233

ATOM 5234 C ASP B 314 7. .981 66. .282 72. .183 1. .00 0. .00 XXXX5234

ATOM 5235 O ASP B 314 8. .725 65. .599 72. .885 1. .00 0. .00 XXXX5235

ATOM 5236 CB ASP B 314 8. .808 68. .549 71. .506 1. .00 0. .00 XXXX5236

ATOM 5237 CG ASP B 314 9. .617 69. .350 70. .503 1. .00 0. .00 XXXX5237

ATOM 5238 OD1 ASP B 314 10. .321 68. .735 69. .673 1. .00 0. .00 XXXX5238

ATOM 5239 OD2 ASP B 314 9. .557 70. .596 70. .551 1. .00 0. .00 XXXX5239

ATOM 5240 N LYS B 315 6. .666 66. .339 72. .369 1. .00 0. .00 XXXX5240

ATOM 5241 CA LYS B 315 6. .015 65. .547 73. .404 1. .00 0. .00 XXXX5241

ATOM 5242 C LYS B 315 6. .016 64. .073 73. .016 1. .00 0. .00 XXXX5242

ATOM 5243 O LYS B 315 6. .233 63. .198 73. .853 1. .00 0. .00 XXXX5243

ATOM 5244 CB LYS B 315 4. .581 66. .028 73. .639 1. .00 0. .00 XXXX5244

ATOM 5245 CG LYS B 315 4. .470 67. .437 74. .198 1. .00 0. .00 XXXX5245

ATOM 5246 CD LYS B 315 3. .013 67. .871 74. .287 1. .00 0. .00 XXXX5246

ATOM 5247 CE LYS B 315 2. .884 69. .291 74. .812 1. .00 0. .00 XXXX5247

ATOM 5248 NZ LYS B 315 3. .465 69. .431 76. .174 1. .00 0. .00 XXXX5248

ATOM 5249 N VAL B 316 5. .771 63. .809 71. .737 1. .00 0. .00 XXXX5249

ATOM 5250 CA VAL B 316 5. .782 62. .447 71. .218 1. .00 0. .00 XXXX5250

ATOM 5251 C VAL B 316 7. .175 61. .832 71. .322 1. .00 0. .00 XXXX5251

ATOM 5252 O VAL B 316 7. .319 60. .666 71. .695 1. .00 0. .00 XXXX5252

ATOM 5253 CB VAL B 316 5. .311 62. .397 69. .754 1. .00 0. .00 XXXX5253

ATOM 5254 CGI VAL B 316 5. .592 61. .029 69. .151 1. .00 0. .00 XXXX5254

ATOM 5255 CG2 VAL B 316 3. .828 62. .729 69. .666 1. .00 0. .00 XXXX5255

ATOM 5256 N ARG B 317 8. .195 62. .617 70. .985 1. .00 0. .00 XXXX5256

ATOM 5257 CA ARG B 317 9. .577 62. .153 71. .061 1. .00 0. .00 XXXX5257

ATOM 5258 C ARG B 317 9. .944 61. .731 72. .481 1. .00 0. .00 XXXX5258

ATOM 5259 O ARG B 317 10. .583 60. .699 72. .685 1. .00 0. .00 XXXX5259

ATOM 5260 CB ARG B 317 10. .545 63. .236 70. .572 1. .00 0. .00 XXXX5260

ATOM 5261 CG ARG B 317 11. .989 62. .754 70. .492 1. .00 0. .00 XXXX5261

ATOM 5262 CD ARG B 317 12. .966 63. .857 70. .107 1. .00 0. .00 XXXX5262

ATOM 5263 NE ARG B 317 12. .669 64. .451 68. .806 1. .00 0. .00 XXXX5263

ATOM 5264 CZ ARG B 317 12. .055 65. .617 68. .639 1. .00 0. .00 XXXX5264

ATOM 5265 NH1 ARG B 317 11. .676 66. .326 69. .692 1. .00 0. .00 XXXX5265

ATOM 5266 NH2 ARG B 317 11. .827 66. .078 67. .417 1. .00 0. .00 XXXX5266

ATOM 5267 N GLU B 318 9. .539 62. .537 73. .456 1. .00 0. .00 XXXX5267

ATOM 5268 CA GLU B 318 9. .828 62. .255 74. .858 1. .00 0. .00 XXXX5268

ATOM 5269 C GLU B 318 9. .098 61. .006 75. .341 1. .00 0. .00 XXXX5269 Attorney Docket No. 35327-522001 WO

ATOM 5270 O GLU B 318 9. .681 60. .154 76. .011 1. .00 0. .00 XXXX5270

ATOM 5271 CB GLU B 318 9. .450 63. .455 75. .732 1. .00 0. .00 XXXX5271

ATOM 5272 CG GLU B 318 9. .682 63. .242 77. .221 1. .00 0. .00 XXXX5272

ATOM 5273 CD GLU B 318 11. .127 62. .913 77. .547 1. .00 0. .00 XXXX5273

ATOM 5274 OE1 GLU B 318 12. .025 63. .390 76. .823 1. .00 0. .00 XXXX5274

ATOM 5275 OE2 GLU B 318 11. .364 62. .175 78. .527 1. .00 0. .00 XXXX5275

ATOM 5276 N ALA B 319 7. .817 60. .905 74. .997 1. .00 0. .00 XXXX5276

ATOM 5277 CA ALA B 319 6. .987 59. .781 75. .423 1. .00 0. .00 XXXX5277

ATOM 5278 C ALA B 319 7. .429 58. .453 74. .809 1. .00 0. .00 XXXX5278

ATOM 5279 O ALA B 319 7. .268 57. .395 75. .418 1. .00 0. .00 XXXX5279

ATOM 5280 CB ALA B 319 5. .527 60. .053 75. .084 1. .00 0. .00 XXXX5280

ATOM 5281 N ALA B 320 7. .991 58. .512 73. .606 1. .00 0. .00 XXXX5281

ATOM 5282 CA ALA B 320 8. .351 57. .304 72. .868 1. .00 0. .00 XXXX5282

ATOM 5283 C ALA B 320 9. .490 56. .530 73. .528 1. .00 0. .00 XXXX5283

ATOM 5284 O ALA B 320 9. .622 55. .322 73. .328 1. .00 0. .00 XXXX5284

ATOM 5285 CB ALA B 320 8. .723 57. .655 71. .437 1. .00 0. .00 XXXX5285

ATOM 5286 N LYS B 321 10. .318 57. .229 74. .299 1. .00 0. .00 XXXX5286

ATOM 5287 CA LYS B 321 11. .463 56. .602 74. .952 1. .00 0. .00 XXXX5287

ATOM 5288 C LYS B 321 11. .047 55. .458 75. .870 1. .00 0. .00 XXXX5288

ATOM 5289 O LYS B 321 10. .317 55. .662 76. .838 1. .00 0. .00 XXXX5289

ATOM 5290 CB LYS B 321 12. .259 57. .634 75. .753 1. .00 0. .00 XXXX5290

ATOM 5291 CG LYS B 321 12. .849 58. .758 74. .922 1. .00 0. .00 XXXX5291

ATOM 5292 CD LYS B 321 13. .701 59. .677 75. .782 1. .00 0. .00 XXXX5292

ATOM 5293 CE LYS B 321 14. .254 60. .834 74. .971 1. .00 0. .00 XXXX5293

ATOM 5294 NZ LYS B 321 14. .951 60. .366 73. .741 1. .00 0. .00 XXXX5294

ATOM 5295 N GLY B 322 11. .520 54. .255 75. .560 1. .00 0. .00 XXXX5295

ATOM 5296 CA GLY B 322 11. .273 53. .101 76. .404 1. .00 0. .00 XXXX5296

ATOM 5297 C GLY B 322 9. .960 52. .378 76. .169 1. .00 0. .00 XXXX5297

ATOM 5298 O GLY B 322 9. .685 51. .372 76. .823 1. .00 0. .00 XXXX5298

ATOM 5299 N ILE B 323 9. .144 52. .876 75. .245 1. .00 0. .00 XXXX5299

ATOM 5300 CA ILE B 323 7. .863 52. .234 74. .968 1. .00 0. .00 XXXX5300

ATOM 5301 C ILE B 323 8. .075 50. .838 74. .394 1. .00 0. .00 XXXX5301

ATOM 5302 O ILE B 323 8. .876 50. .641 73. .479 1. .00 0. .00 XXXX5302

ATOM 5303 CB ILE B 323 7. .001 53. .054 73. .995 1. .00 0. .00 XXXX5303

ATOM 5304 CGI ILE B 323 6. .486 54. .322 74. .675 1. .00 0. .00 XXXX5304

ATOM 5305 CD1 ILE B 323 5. .444 55. .063 73. .863 1. .00 0. .00 XXXX5305

ATOM 5306 CG2 ILE B 323 5. .825 52. .224 73. .504 1. .00 0. .00 XXXX5306

ATOM 5307 N GLU B 324 7. .347 49. .872 74. .944 1. .00 0. .00 XXXX5307

ATOM 5308 CA GLU B 324 7. .476 48. .483 74. .533 1. .00 0. .00 XXXX5308

ATOM 5309 C GLU B 324 6. .342 48. .087 73. .599 1. .00 0. .00 XXXX5309

ATOM 5310 O GLU B 324 5. .323 48. .772 73. .516 1. .00 0. .00 XXXX5310

ATOM 5311 CB GLU B 324 7. .493 47. .566 75. .756 1. .00 0. .00 XXXX5311

ATOM 5312 CG GLU B 324 8. .595 47. .882 76. .752 1. .00 0. .00 XXXX5312

ATOM 5313 CD GLU B 324 8. .403 47. .169 78. .074 1. .00 0. .00 XXXX5313

ATOM 5314 OE1 GLU B 324 7. .240 46. .893 78. .435 1. .00 0. .00 XXXX5314

ATOM 5315 OE2 GLU B 324 9. .412 46. .886 78. .753 1. .00 0. .00 XXXX5315

ATOM 5316 N PHE B 325 6. .530 46. .981 72. .891 1. .00 0. .00 XXXX5316

ATOM 5317 CA PHE B 325 5. .480 46. .431 72. .049 1. .00 0. .00 XXXX5317

ATOM 5318 C PHE B 325 5. .695 44. .936 71. .869 1. .00 0. .00 XXXX5318

ATOM 5319 O PHE B 325 6. .798 44. .494 71. .546 1. .00 0. .00 XXXX5319

ATOM 5320 CB PHE B 325 5. .449 47. .137 70. .690 1. .00 0. .00 XXXX5320

ATOM 5321 CG PHE B 325 4. .246 46. .796 69. .855 1. .00 0. .00 XXXX5321

ATOM 5322 CD1 PHE B 325 2. .999 47. .310 70. .171 1. .00 0. .00 XXXX5322

ATOM 5323 CD2 PHE B 325 4. .361 45. .964 68. .753 1. .00 0. .00 XXXX5323

ATOM 5324 CE1 PHE B 325 1. .888 47. .000 69. .404 1. .00 0. .00 XXXX5324

ATOM 5325 CE2 PHE B 325 3. .255 45. .651 67. .982 1. .00 0. .00 XXXX5325

ATOM 5326 CZ PHE B 325 2. .018 46. .169 68. .309 1. .00 0. .00 XXXX5326

ATOM 5327 N ASN B 326 4. .641 44. .158 72. .081 1. .00 0. .00 XXXX5327

ATOM 5328 CA ASN B 326 4. .706 42. .726 71. .830 1. .00 0. .00 XXXX5328

ATOM 5329 C ASN B 326 4. .562 42. .432 70. .340 1. .00 0. .00 XXXX5329

ATOM 5330 O ASN B 326 3. .502 42. .030 69. .866 1. .00 0. .00 XXXX5330

ATOM 5331 CB ASN B 326 3. .640 41. .992 72. .649 1. .00 0. .00 XXXX5331

ATOM 5332 CG ASN B 326 2. .278 42. .651 72. .563 1. .00 0. .00 XXXX5332

ATOM 5333 OD1 ASN B 326 2. .168 43. .877 72. .548 1. .00 0. .00 XXXX5333

ATOM 5334 ND2 ASN B 326 1. .229 41. .837 72. .504 1. .00 0. .00 XXXX5334

ATOM 5335 N ALA B 327 5. .654 42. .629 69. .609 1. .00 0. .00 XXXX5335

ATOM 5336 CA ALA B 327 5. .659 42. .470 68. .160 1. .00 0. .00 XXXX5336 Attorney Docket No. 35327-522001 WO

ATOM 5337 C ALA B 327 5. .620 40. .999 67. .761 1. .00 0. .00 XXXX5337

ATOM 5338 O ALA B 327 5. .946 40. .125 68. .562 1. .00 0. .00 XXXX5338

ATOM 5339 CB ALA B 327 6. .882 43. .150 67. .560 1. .00 0. .00 XXXX5339

ATOM 5340 N PRO B 328 5. .204 40. .725 66. .517 1. .00 0. .00 XXXX5340

ATOM 5341 CA PRO B 328 5. .196 39. .375 65. .943 1. .00 0. .00 XXXX5341

ATOM 5342 C PRO B 328 6. .546 38. .668 66. .058 1. .00 0. .00 XXXX5342

ATOM 5343 O PRO B 328 6. .590 37. .457 66. .268 1. .00 0. .00 XXXX5343

ATOM 5344 CB PRO B 328 4. .839 39. .628 64. .477 1. .00 0. .00 XXXX5344

ATOM 5345 CG PRO B 328 4. .008 40. .863 64. .517 1. .00 0. .00 XXXX5345

ATOM 5346 CD PRO B 328 4. .633 41. .718 65. .589 1. .00 0. .00 XXXX5346

ATOM 5347 N GLU B 329 7. .633 39. .424 65. .930 1. .00 0. .00 XXXX5347

ATOM 5348 CA GLU B 329 8. .973 38. .845 65. .961 1. .00 0. .00 XXXX5348

ATOM 5349 C GLU B 329 9. .391 38. .505 67. .385 1. .00 0. .00 XXXX5349

ATOM 5350 O GLU B 329 10. .335 37. .747 67. .605 1. .00 0. .00 XXXX5350

ATOM 5351 CB GLU B 329 9. .992 39. .805 65. .347 1. .00 0. .00 XXXX5351

ATOM 5352 CG GLU B 329 10. .286 41. .019 66. .217 1. .00 0. .00 XXXX5352

ATOM 5353 CD GLU B 329 11. .470 41. .829 65. .720 1. .00 0. .00 XXXX5353

ATOM 5354 OE1 GLU B 329 11. .365 42. .435 64. .634 1. .00 0. .00 XXXX5354

ATOM 5355 OE2 GLU B 329 12. .503 41. .863 66. .422 1. .00 0. .00 XXXX5355

ATOM 5356 N GLY B 330 8. .679 39. .073 68. .349 1. .00 0. .00 XXXX5356

ATOM 5357 CA GLY B 330 9. .061 38. .973 69. .744 1. .00 0. .00 XXXX5357

ATOM 5358 C GLY B 330 8. .975 40. .348 70. .370 1. .00 0. .00 XXXX5358

ATOM 5359 O GLY B 330 8. .512 41. .291 69. .727 1. .00 0. .00 XXXX5359

ATOM 5360 N PRO B 331 9. .414 40. .476 71. .629 1. .00 0. .00 XXXX5360

ATOM 5361 CA PRO B 331 9. .332 41. .777 72. .296 1. .00 0. .00 XXXX5361

ATOM 5362 C PRO B 331 10. .270 42. .796 71. .658 1. .00 0. .00 XXXX5362

ATOM 5363 O PRO B 331 11. .432 42. .489 71. .397 1. .00 0. .00 XXXX5363

ATOM 5364 CB PRO B 331 9. .754 41. .464 73. .735 1. .00 0. .00 XXXX5364

ATOM 5365 CG PRO B 331 10. .588 40. .236 73. .626 1. .00 0. .00 XXXX5365

ATOM 5366 CD PRO B 331 10. .008 39. .442 72. .493 1. .00 0. .00 XXXX5366

ATOM 5367 N VAL B 332 9. .758 43. .995 71. .408 1. .00 0. .00 XXXX5367

ATOM 5368 CA VAL B 332 10. .586 45. .090 70. .926 1. .00 0. .00 XXXX5368

ATOM 5369 C VAL B 332 10. .400 46. .306 71. .818 1. .00 0. .00 XXXX5369

ATOM 5370 O VAL B 332 9. .480 46. .359 72. .633 1. .00 0. .00 XXXX5370

ATOM 5371 CB VAL B 332 10. .260 45. .468 69. .465 1. .00 0. .00 XXXX5371

ATOM 5372 CGI VAL B 332 10. .520 44. .290 68. .541 1. .00 0. .00 XXXX5372

ATOM 5373 CG2 VAL B 332 8. .820 45. .952 69. .343 1. .00 0. .00 XXXX5373

ATOM 5374 N LYS B 333 11. .283 47. .282 71. .658 1. .00 0. .00 XXXX5374

ATOM 5375 CA LYS B 333 11. .265 48. .468 72. .497 1. .00 0. .00 XXXX5375

ATOM 5376 C LYS B 333 12. .003 49. .612 71. .824 1. .00 0. .00 XXXX5376

ATOM 5377 O LYS B 333 13. .043 49. .405 71. .202 1. .00 0. .00 XXXX5377

ATOM 5378 CB LYS B 333 11. .890 48. .151 73. .858 1. .00 0. .00 XXXX5378

ATOM 5379 CG LYS B 333 12. .158 49. .357 74. .735 1. .00 0. .00 XXXX5379

ATOM 5380 CD LYS B 333 13. .097 48. .984 75. .872 1. .00 0. .00 XXXX5380

ATOM 5381 CE LYS B 333 13. .652 50. .216 76. .561 1. .00 0. .00 XXXX5381

ATOM 5382 NZ LYS B 333 14. .533 51. .020 75. .671 1. .00 0. .00 XXXX5382

ATOM 5383 N ILE B 334 11. .464 50. .820 71. .947 1. .00 0. .00 XXXX5383

ATOM 5384 CA ILE B 334 12. .143 51. .992 71. .417 1. .00 0. .00 XXXX5384

ATOM 5385 C ILE B 334 13. .299 52. .378 72. .331 1. .00 0. .00 XXXX5385

ATOM 5386 O ILE B 334 13. .099 52. .725 73. .496 1. .00 0. .00 XXXX5386

ATOM 5387 CB ILE B 334 11. .185 53. .185 71. .254 1. .00 0. .00 XXXX5387

ATOM 5388 CGI ILE B 334 10. .079 52. .839 70. .255 1. .00 0. .00 XXXX5388

ATOM 5389 CG2 ILE B 334 11. .945 54. .415 70. .793 1. .00 0. .00 XXXX5389

ATOM 5390 CD1 ILE B 334 9. .150 53. .990 69. .938 1. .00 0. .00 XXXX5390

ATOM 5391 N ASP B 335 14. .510 52. .316 71. .788 1. .00 0. .00 XXXX5391

ATOM 5392 CA ASP B 335 15. .706 52. .701 72. .520 1. .00 0. .00 XXXX5392

ATOM 5393 C ASP B 335 15. .749 54. .218 72. .669 1. .00 0. .00 XXXX5393

ATOM 5394 O ASP B 335 15. .941 54. .940 71. .691 1. .00 0. .00 XXXX5394

ATOM 5395 CB ASP B 335 16. .959 52. .185 71. .803 1. .00 0. .00 XXXX5395

ATOM 5396 CG ASP B 335 18. .228 52. .362 72. .623 1. .00 0. .00 XXXX5396

ATOM 5397 OD1 ASP B 335 18. .221 53. .145 73. .596 1. .00 0. .00 XXXX5397

ATOM 5398 OD2 ASP B 335 19. .238 51. .706 72. .291 1. .00 0. .00 XXXX5398

ATOM 5399 N GLY B 336 15. .559 54. .693 73. .897 1. .00 0. .00 XXXX5399

ATOM 5400 CA GLY B 336 15. .595 56. .116 74. .185 1. .00 0. .00 XXXX5400

ATOM 5401 C GLY B 336 16. .897 56. .781 73. .777 1. .00 0. .00 XXXX5401

ATOM 5402 O GLY B 336 16. .933 57. .984 73. .519 1. .00 0. .00 XXXX5402

ATOM 5403 N ASP B 337 17. .970 55. .999 73. .724 1. .00 0. .00 XXXX5403 Attorney Docket No. 35327-522001 WO

ATOM 5404 CA ASP B 337 19. .285 56. .520 73. .363 1. .00 0. .00 XXXX5404

ATOM 5405 C ASP B 337 19. .370 57. .006 71. .917 1. .00 0. .00 XXXX5405

ATOM 5406 O ASP B 337 20. .122 57. .932 71. .612 1. .00 0. .00 XXXX5406

ATOM 5407 CB ASP B 337 20. .360 55. .455 73. .597 1. .00 0. .00 XXXX5407

ATOM 5408 CG ASP B 337 20. .677 55. .256 75. .065 1. .00 0. .00 XXXX5408

ATOM 5409 OD1 ASP B 337 20. .259 56. .098 75. .887 1. .00 0. .00 XXXX5409

ATOM 5410 OD2 ASP B 337 21. .350 54. .257 75. .395 1. .00 0. .00 XXXX5410

ATOM 5411 N ASN B 338 18. .599 56. .392 71. .025 1. .00 0. .00 XXXX5411

ATOM 5412 CA ASN B 338 18. .787 56. .640 69. .600 1. .00 0. .00 XXXX5412

ATOM 5413 C ASN B 338 17. .537 56. .467 68. .742 1. .00 0. .00 XXXX5413

ATOM 5414 O ASN B 338 17. .603 56. .574 67. .517 1. .00 0. .00 XXXX5414

ATOM 5415 CB ASN B 338 19. .890 55. .720 69. .074 1. .00 0. .00 XXXX5415

ATOM 5416 CG ASN B 338 19. .653 54. .265 69. .433 1. .00 0. .00 XXXX5416

ATOM 5417 OD1 ASN B 338 18. .513 53. .800 69. .470 1. .00 0. .00 XXXX5417

ATOM 5418 ND2 ASN B 338 20. .729 53. .542 69. .708 1. .00 0. .00 XXXX5418

ATOM 5419 N GLN B 339 16. .406 56. .198 69. .386 1. .00 0. .00 XXXX5419

ATOM 5420 CA GLN B 339 15. .128 56. .094 68. .689 1. .00 0. .00 XXXX5420

ATOM 5421 C GLN B 339 15. .096 54. .936 67. .684 1. .00 0. .00 XXXX5421

ATOM 5422 O GLN B 339 14. .257 54. .903 66. .782 1. .00 0. .00 XXXX5422

ATOM 5423 CB GLN B 339 14. .808 57. .425 68. .000 1. .00 0. .00 XXXX5423

ATOM 5424 CG GLN B 339 14. .834 58. .603 68. .971 1. .00 0. .00 XXXX5424

ATOM 5425 CD GLN B 339 14. .282 59. .887 68. .384 1. .00 0. .00 XXXX5425

ATOM 5426 OE1 GLN B 339 14. .042 60. .856 69. .105 1. .00 0. .00 XXXX5426

ATOM 5427 NE2 GLN B 339 14. .080 59. .905 67. .072 1. .00 0. .00 XXXX5427

ATOM 5428 N HIS B 340 16. .022 53. .993 67. .845 1. .00 0. .00 XXXX5428

ATOM 5429 CA HIS B 340 15. .967 52. .713 67. .142 1. .00 0. .00 XXXX5429

ATOM 5430 C HIS B 340 15. .188 51. .696 67. .979 1. .00 0. .00 XXXX5430

ATOM 5431 O HIS B 340 14. .705 52. .021 69. .063 1. .00 0. .00 XXXX5431

ATOM 5432 CB HIS B 340 17. .375 52. .182 66. .844 1. .00 0. .00 XXXX5432

ATOM 5433 CG HIS B 340 18. .114 52. .959 65. .796 1. .00 0. .00 XXXX5433

ATOM 5434 ND1 HIS B 340 18. .396 54. .301 65. .920 1. .00 0. .00 XXXX5434

ATOM 5435 CD2 HIS B 340 18. .638 52. .570 64. .610 1. .00 0. .00 XXXX5435

ATOM 5436 CE1 HIS B 340 19. .060 54. .708 64. .851 1. .00 0. .00 XXXX5436

ATOM 5437 NE2 HIS B 340 19. .219 53. .680 64. .041 1. .00 0. .00 XXXX5437

ATOM 5438 N LEU B 341 15. .072 50. .469 67. .478 1. .00 0. .00 XXXX5438

ATOM 5439 CA LEU B 341 14. .372 49. .403 68. .197 1. .00 0. .00 XXXX5439

ATOM 5440 C LEU B 341 15. .306 48. .319 68. .727 1. .00 0. .00 XXXX5440

ATOM 5441 O LEU B 341 16. .285 47. .956 68. .072 1. .00 0. .00 XXXX5441

ATOM 5442 CB LEU B 341 13. .326 48. .740 67. .294 1. .00 0. .00 XXXX5442

ATOM 5443 CG LEU B 341 11. .979 49. .408 67. .031 1. .00 0. .00 XXXX5443

ATOM 5444 CD1 LEU B 341 11. .133 48. .510 66. .140 1. .00 0. .00 XXXX5444

ATOM 5445 CD2 LEU B 341 11. .254 49. .706 68. .335 1. .00 0. .00 XXXX5445

ATOM 5446 N TYR B 342 14. .997 47. .804 69. .914 1. .00 0. .00 XXXX5446

ATOM 5447 CA TYR B 342 15. .530 46. .515 70. .337 1. .00 0. .00 XXXX5447

ATOM 5448 C TYR B 342 14. .916 45. .436 69. .455 1. .00 0. .00 XXXX5448

ATOM 5449 O TYR B 342 13. .693 45. .305 69. .400 1. .00 0. .00 XXXX5449

ATOM 5450 CB TYR B 342 15. .215 46. .227 71. .808 1. .00 0. .00 XXXX5450

ATOM 5451 CG TYR B 342 16. .087 46. .946 72. .813 1. .00 0. .00 XXXX5451

ATOM 5452 CD1 TYR B 342 16. .022 48. .325 72. .965 1. .00 0. .00 XXXX5452

ATOM 5453 CD2 TYR B 342 16. .962 46. .238 73. .628 1. .00 0. .00 XXXX5453

ATOM 5454 CE1 TYR B 342 16. .815 48. .980 73. .893 1. .00 0. .00 XXXX5454

ATOM 5455 CE2 TYR B 342 17. .755 46. .881 74. .558 1. .00 0. .00 XXXX5455

ATOM 5456 CZ TYR B 342 17. .679 48. .252 74. .686 1. .00 0. .00 XXXX5456

ATOM 5457 OH TYR B 342 18. .470 48. .896 75. .611 1. .00 0. .00 XXXX5457

ATOM 5458 N LYS B 343 15. .750 44. .663 68. .768 1. .00 0. .00 XXXX5458

ATOM 5459 CA LYS B 343 15. .235 43. .618 67. .890 1. .00 0. .00 XXXX5459

ATOM 5460 C LYS B 343 16. .035 42. .323 68. .012 1. .00 0. .00 XXXX5460

ATOM 5461 O LYS B 343 17. .238 42. .339 68. .280 1. .00 0. .00 XXXX5461

ATOM 5462 CB LYS B 343 15. .232 44. .098 66. .434 1. .00 0. .00 XXXX5462

ATOM 5463 CG LYS B 343 14. .625 45. .484 66. .236 1. .00 0. .00 XXXX5463

ATOM 5464 CD LYS B 343 14. .397 45. .797 64. .763 1. .00 0. .00 XXXX5464

ATOM 5465 CE LYS B 343 13. .212 45. .022 64. .208 1. .00 0. .00 XXXX5465

ATOM 5466 NZ LYS B 343 13. .006 45. .288 62. .758 1. .00 0. .00 XXXX5466

ATOM 5467 N THR B 344 15. .351 41. .202 67. .813 1. .00 0. .00 XXXX5467

ATOM 5468 CA THR B 344 16. .000 39. .901 67. .773 1. .00 0. .00 XXXX5468

ATOM 5469 C THR B 344 16. .680 39. .717 66. .424 1. .00 0. .00 XXXX5469

ATOM 5470 O THR B 344 16. .161 40. .158 65. .401 1. .00 0. .00 XXXX5470 Attorney Docket No. 35327-522001 WO

ATOM 5471 CB THR B 344 14. .992 38. .762 68. .002 1. .00 0. .00 XXXX5471

ATOM 5472 OG1 THR B 344 14. .382 38. .912 69. .290 1. .00 0. .00 XXXX5472

ATOM 5473 CG2 THR B 344 15. .683 37. .408 67. .915 1. .00 0. .00 XXXX5473

ATOM 5474 N VAL B 345 17. .839 39. .070 66. .419 1. .00 0. .00 XXXX5474

ATOM 5475 CA VAL B 345 18. .536 38. .796 65. .169 1. .00 0. .00 XXXX5475

ATOM 5476 C VAL B 345 18. .310 37. .360 64. .720 1. .00 0. .00 XXXX5476

ATOM 5477 O VAL B 345 18. .418 36. .427 65. .513 1. .00 0. .00 XXXX5477

ATOM 5478 CB VAL B 345 20. .046 39. .052 65. .292 1. .00 0. .00 XXXX5478

ATOM 5479 CGI VAL B 345 20. .734 38. .801 63. .958 1. .00 0. .00 XXXX5479

ATOM 5480 CG2 VAL B 345 20. .302 40. .471 65. .772 1. .00 0. .00 XXXX5480

ATOM 5481 N ARG B 346 17. .994 37. .197 63. .441 1. .00 0. .00 XXXX5481

ATOM 5482 CA ARG B 346 17. .754 35. .885 62. .854 1. .00 0. .00 XXXX5482

ATOM 5483 C ARG B 346 18. .415 35. .679 61. .502 1. .00 0. .00 XXXX5483

ATOM 5484 O ARG B 346 18. .407 36. .562 60. .646 1. .00 0. .00 XXXX5484

ATOM 5485 CB ARG B 346 16. .252 35. .618 62. .715 1. .00 0. .00 XXXX5485

ATOM 5486 CG ARG B 346 15. .426 35. .874 63. .958 1. .00 0. .00 XXXX5486

ATOM 5487 CD ARG B 346 13. .969 35. .529 63. .684 1. .00 0. .00 XXXX5487

ATOM 5488 NE ARG B 346 13. .293 35. .039 64. .884 1. .00 0. .00 XXXX5488

ATOM 5489 CZ ARG B 346 12. .623 35. .775 65. .761 1. .00 0. .00 XXXX5489

ATOM 5490 NH1 ARG B 346 12. .507 37. .086 65. .604 1. .00 0. .00 XXXX5490

ATOM 5491 NH2 ARG B 346 12. .062 35. .183 66. .807 1. .00 0. .00 XXXX5491

ATOM 5492 N ILE B 347 18. .986 34. .492 61. .327 1. .00 0. .00 XXXX5492

ATOM 5493 CA ILE B 347 19. .544 34. .082 60. .050 1. .00 0. .00 XXXX5493

ATOM 5494 C ILE B 347 18. .815 32. .832 59. .569 1. .00 0. .00 XXXX5494

ATOM 5495 O ILE B 347 18. .560 31. .914 60. .350 1. .00 0. .00 XXXX5495

ATOM 5496 CB ILE B 347 21. .054 33. .801 60. .155 1. .00 0. .00 XXXX5496

ATOM 5497 CGI ILE B 347 21. .802 35. .063 60. .595 1. .00 0. .00 XXXX5497

ATOM 5498 CG2 ILE B 347 21. .591 33. .270 58. .834 1. .00 0. .00 XXXX5498

ATOM 5499 CD1 ILE B 347 23. .288 34. .853 60. .812 1. .00 0. .00 XXXX5499

ATOM 5500 N GLY B 348 18. .471 32. .796 58. .287 1. .00 0. .00 XXXX5500

ATOM 5501 CA GLY B 348 17. .712 31. .681 57. .754 1. .00 0. .00 XXXX5501

ATOM 5502 C GLY B 348 18. .022 31. .370 56. .306 1. .00 0. .00 XXXX5502

ATOM 5503 O GLY B 348 18. .645 32. .169 55. .606 1. .00 0. .00 XXXX5503

ATOM 5504 N GLU B 349 17. .580 30. .201 55. .853 1. .00 0. .00 XXXX5504

ATOM 5505 CA GLU B 349 17. .726 29. .826 54. .455 1. .00 0. .00 XXXX5505

ATOM 5506 C GLU B 349 16. .364 29. .780 53. .773 1. .00 0. .00 XXXX5506

ATOM 5507 O GLU B 349 15. .357 29. .429 54. .388 1. .00 0. .00 XXXX5507

ATOM 5508 CB GLU B 349 18. .441 28. .479 54. .324 1. .00 0. .00 XXXX5508

ATOM 5509 CG GLU B 349 17. .690 27. .298 54. .907 1. .00 0. .00 XXXX5509

ATOM 5510 CD GLU B 349 18. .375 25. .978 54. .608 1. .00 0. .00 XXXX5510

ATOM 5511 OE1 GLU B 349 19. .012 25. .867 53. .538 1. .00 0. .00 XXXX5511

ATOM 5512 OE2 GLU B 349 18. .280 25. .053 55. .442 1. .00 0. .00 XXXX5512

ATOM 5513 N ILE B 350 16. .347 30. .132 52. .493 1. .00 0. .00 XXXX5513

ATOM 5514 CA ILE B 350 15. .107 30. .219 51. .733 1. .00 0. .00 XXXX5514

ATOM 5515 C ILE B 350 14. .618 28. .843 51. .294 1. .00 0. .00 XXXX5515

ATOM 5516 O ILE B 350 15. .379 28. .048 50. .742 1. .00 0. .00 XXXX5516

ATOM 5517 CB ILE B 350 15. .283 31. .119 50. .497 1. .00 0. .00 XXXX5517

ATOM 5518 CGI ILE B 350 15. .787 32. .499 50. .925 1. .00 0. .00 XXXX5518

ATOM 5519 CG2 ILE B 350 13. .977 31. .224 49. .717 1. .00 0. .00 XXXX5519

ATOM 5520 CD1 ILE B 350 16. .269 33. .361 49. .779 1. .00 0. .00 XXXX5520

ATOM 5521 N LEU B 351 13. .341 28. .572 51. .546 1. .00 0. .00 XXXX5521

ATOM 5522 CA LEU B 351 12. .749 27. .280 51. .221 1. .00 0. .00 XXXX5522

ATOM 5523 C LEU B 351 12. .140 27. .281 49. .824 1. .00 0. .00 XXXX5523

ATOM 5524 O LEU B 351 12. .011 28. .328 49. .189 1. .00 0. .00 XXXX5524

ATOM 5525 CB LEU B 351 11. .684 26. .904 52. .254 1. .00 0. .00 XXXX5525

ATOM 5526 CG LEU B 351 12. .156 26. .760 53. .702 1. .00 0. .00 XXXX5526

ATOM 5527 CD1 LEU B 351 10. .974 26. .540 54. .638 1. .00 0. .00 XXXX5527

ATOM 5528 CD2 LEU B 351 13. .167 25. .625 53. .827 1. .00 0. .00 XXXX5528

ATOM 5529 N GLU B 352 11. .769 26. .094 49. .355 1. .00 0. .00 XXXX5529

ATOM 5530 CA GLU B 352 11. .230 25. .916 48. .013 1. .00 0. .00 XXXX5530

ATOM 5531 C GLU B 352 9. .979 26. .761 47. .783 1. .00 0. .00 XXXX5531

ATOM 5532 O GLU B 352 9. .725 27. .215 46. .667 1. .00 0. .00 XXXX5532

ATOM 5533 CB GLU B 352 10. .916 24. .441 47. .765 1. .00 0. .00 XXXX5533

ATOM 5534 CG GLU B 352 10. .379 24. .136 46. .378 1. .00 0. .00 XXXX5534

ATOM 5535 CD GLU B 352 9. .928 22. .696 46. .238 1. .00 0. .00 XXXX5535

ATOM 5536 OE1 GLU B 352 9. .160 22. .228 47. .103 1. .00 0. .00 XXXX5536

ATOM 5537 OE2 GLU B 352 10. .348 22. .031 45. .267 1. .00 0. .00 XXXX5537 Attorney Docket No. 35327-522001 WO

ATOM 5538 N ASN B 353 9. .204 26. .977 48. .842 1. .00 0. .00 XXXX5538

ATOM 5539 CA ASN B 353 7. .974 27. .756 48. .739 1. .00 0. .00 XXXX5539

ATOM 5540 C ASN B 353 8. .188 29. .245 48. .999 1. .00 0. .00 XXXX5540

ATOM 5541 O ASN B 353 7. .231 30. .016 49. .065 1. .00 0. .00 XXXX5541

ATOM 5542 CB ASN B 353 6. .916 27. .206 49. .701 1. .00 0. .00 XXXX5542

ATOM 5543 CG ASN B 353 7. .343 27. .289 51. .157 1. .00 0. .00 XXXX5543

ATOM 5544 OD1 ASN B 353 8. .411 27. .809 51. .479 1. .00 0. .00 XXXX5544

ATOM 5545 ND2 ASN B 353 6. .501 26. .775 52. .046 1. .00 0. .00 XXXX5545

ATOM 5546 N GLY B 354 9. .447 29. .645 49. .147 1. .00 0. .00 XXXX5546

ATOM 5547 CA GLY B 354 9. .781 31. .042 49. .364 1. .00 0. .00 XXXX5547

ATOM 5548 C GLY B 354 9. .784 31. .462 50. .821 1. .00 0. .00 XXXX5548

ATOM 5549 O GLY B 354 10. .135 32. .597 51. .144 1. .00 0. .00 XXXX5549

ATOM 5550 N GLN B 355 9. .391 30. .553 51. .707 1. .00 0. .00 XXXX5550

ATOM 5551 CA GLN B 355 9. .433 30. .827 53. .140 1. .00 0. .00 XXXX5551

ATOM 5552 C GLN B 355 10. .834 30. .608 53. .697 1. .00 0. .00 XXXX5552

ATOM 5553 O GLN B 355 11. .703 30. .060 53. .018 1. .00 0. .00 XXXX5553

ATOM 5554 CB GLN B 355 8. .424 29. .956 53. .888 1. .00 0. .00 XXXX5554

ATOM 5555 CG GLN B 355 6. .977 30. .310 53. .591 1. .00 0. .00 XXXX5555

ATOM 5556 CD GLN B 355 6. .592 31. .672 54. .137 1. .00 0. .00 XXXX5556

ATOM 5557 OE1 GLN B 355 6. .669 31. .915 55. .340 1. .00 0. .00 XXXX5557

ATOM 5558 NE2 GLN B 355 6. .179 32. .569 53. .251 1. .00 0. .00 XXXX5558

ATOM 5559 N ILE B 356 11. .050 31. .039 54. .936 1. .00 0. .00 XXXX5559

ATOM 5560 CA ILE B 356 12. .373 30. .970 55. .544 1. .00 0. .00 XXXX5560

ATOM 5561 C ILE B 356 12. .469 29. .919 56. .643 1. .00 0. .00 XXXX5561

ATOM 5562 O ILE B 356 11. .589 29. .811 57. .498 1. .00 0. .00 XXXX5562

ATOM 5563 CB ILE B 356 12. .787 32. .330 56. .137 1. .00 0. .00 XXXX5563

ATOM 5564 CGI ILE B 356 12. .616 33. .439 55. .099 1. .00 0. .00 XXXX5564

ATOM 5565 CG2 ILE B 356 14. .226 32. .280 56. .637 1. .00 0. .00 XXXX5565

ATOM 5566 CD1 ILE B 356 13. .444 33. .238 53. .847 1. .00 0. .00 XXXX5566

ATOM 5567 N ARG B 357 13. .548 29. .146 56. .605 1. .00 0. .00 XXXX5567

ATOM 5568 CA ARG B 357 13. .885 28. .232 57. .688 1. .00 0. .00 XXXX5568

ATOM 5569 C ARG B 357 14. .977 28. .855 58. .548 1. .00 0. .00 XXXX5569

ATOM 5570 O ARG B 357 16. .091 29. .086 58. .078 1. .00 0. .00 XXXX5570

ATOM 5571 CB ARG B 357 14. .335 26. .877 57. .136 1. .00 0. .00 XXXX5571

ATOM 5572 CG ARG B 357 14. .807 25. .888 58. .192 1. .00 0. .00 XXXX5572

ATOM 5573 CD ARG B 357 15. .183 24. .558 57. .557 1. .00 0. .00 XXXX5573

ATOM 5574 NE ARG B 357 15. .688 23. .594 58. .531 1. .00 0. .00 XXXX5574

ATOM 5575 CZ ARG B 357 16. .976 23. .328 58. .723 1. .00 0. .00 XXXX5575

ATOM 5576 NH1 ARG B 357 17. .898 23. .950 58. .001 1. .00 0. .00 XXXX5576

ATOM 5577 NH2 ARG B 357 17. .343 22. .436 59. .632 1. .00 0. .00 XXXX5577

ATOM 5578 N GLU B 358 14. .654 29. .137 59. .806 1. .00 0. .00 XXXX5578

ATOM 5579 CA GLU B 358 15. .604 29. .787 60. .700 1. .00 0. .00 XXXX5579

ATOM 5580 C GLU B 358 16. .749 28. .843 61. .047 1. .00 0. .00 XXXX5580

ATOM 5581 O GLU B 358 16. .526 27. .702 61. .450 1. .00 0. .00 XXXX5581

ATOM 5582 CB GLU B 358 14. .904 30. .266 61. .973 1. .00 0. .00 XXXX5582

ATOM 5583 CG GLU B 358 15. .826 30. .928 62. .985 1. .00 0. .00 XXXX5583

ATOM 5584 CD GLU B 358 15. .075 31. .477 64. .183 1. .00 0. .00 XXXX5584

ATOM 5585 OE1 GLU B 358 14. .379 32. .503 64. .032 1. .00 0. .00 XXXX5585

ATOM 5586 OE2 GLU B 358 15. .178 30. .880 65. .276 1. .00 0. .00 XXXX5586

ATOM 5587 N LEU B 359 17. .975 29. .327 60. .882 1. .00 0. .00 XXXX5587

ATOM 5588 CA LEU B 359 19. .161 28. .532 61. .175 1. .00 0. .00 XXXX5588

ATOM 5589 C LEU B 359 19. .821 28. .978 62. .474 1. .00 0. .00 XXXX5589

ATOM 5590 O LEU B 359 20. .482 28. .190 63. .149 1. .00 0. .00 XXXX5590

ATOM 5591 CB LEU B 359 20. .163 28. .628 60. .022 1. .00 0. .00 XXXX5591

ATOM 5592 CG LEU B 359 19. .655 28. .235 58. .632 1. .00 0. .00 XXXX5592

ATOM 5593 CD1 LEU B 359 20. .733 28. .465 57. .584 1. .00 0. .00 XXXX5593

ATOM 5594 CD2 LEU B 359 19. .182 26. .789 58. .613 1. .00 0. .00 XXXX5594

ATOM 5595 N TRP B 360 19. .634 30. .246 62. .820 1. .00 0. .00 XXXX5595

ATOM 5596 CA TRP B 360 20. .316 30. .839 63. .962 1. .00 0. .00 XXXX5596

ATOM 5597 C TRP B 360 19. .603 32. .107 64. .417 1. .00 0. .00 XXXX5597

ATOM 5598 O TRP B 360 19. .006 32. .813 63. .606 1. .00 0. .00 XXXX5598

ATOM 5599 CB TRP B 360 21. .773 31. .150 63. .606 1. .00 0. .00 XXXX5599

ATOM 5600 CG TRP B 360 22. .544 31. .817 64. .706 1. .00 0. .00 XXXX5600

ATOM 5601 CD1 TRP B 360 23. .321 31. .208 65. .647 1. .00 0. .00 XXXX5601

ATOM 5602 CD2 TRP B 360 22. .611 33. .223 64. .979 1. .00 0. .00 XXXX5602

ATOM 5603 NE1 TRP B 360 23. .869 32. .146 66. .488 1. .00 0. .00 XXXX5603

ATOM 5604 CE2 TRP B 360 23. .448 33. .391 66. .101 1. .00 0. .00 XXXX5604 Attorney Docket No. 35327-522001 WO

ATOM 5605 CE3 TRP B 360 22. .043 34. .355 64. .386 1. .00 0. .00 XXXX5605

ATOM 5606 CZ2 TRP B 360 23. .733 34. .644 66. .639 1. .00 0. .00 XXXX5606

ATOM 5607 CZ3 TRP B 360 22. .326 35. .599 64. .923 1. .00 0. .00 XXXX5607

ATOM 5608 CH2 TRP B 360 23. .164 35. .733 66. .038 1. .00 0. .00 XXXX5608

ATOM 5609 N LYS B 361 19. .668 32. .390 65. .714 1. .00 0. .00 XXXX5609

ATOM 5610 CA LYS B 361 19. .119 33. .630 66. .251 1. .00 0. .00 XXXX5610

ATOM 5611 C LYS B 361 19. .740 33. .974 67. .600 1. .00 0. .00 XXXX5611

ATOM 5612 O LYS B 361 20. .345 33. .121 68. .248 1. .00 0. .00 XXXX5612

ATOM 5613 CB LYS B 361 17. .599 33. .530 66. .396 1. .00 0. .00 XXXX5613

ATOM 5614 CG LYS B 361 17. .151 32. .647 67. .551 1. .00 0. .00 XXXX5614

ATOM 5615 CD LYS B 361 15. .664 32. .800 67. .826 1. .00 0. .00 XXXX5615

ATOM 5616 CE LYS B 361 15. .195 31. .819 68. .888 1. .00 0. .00 XXXX5616

ATOM 5617 NZ LYS B 361 13. .750 31. .999 69. .205 1. .00 0. .00 XXXX5617

ATOM 5618 N THR B 362 19. .588 35. .228 68. .016 1. .00 0. .00 XXXX5618

ATOM 5619 CA THR B 362 19. .967 35. .630 69. .364 1. .00 0. .00 XXXX5619

ATOM 5620 C THR B 362 18. .896 35. .174 70. .352 1. .00 0. .00 XXXX5620

ATOM 5621 O THR B 362 17. .724 35. .058 69. .996 1. .00 0. .00 XXXX5621

ATOM 5622 CB THR B 362 20. .165 37. .154 69. .476 1. .00 0. .00 XXXX5622

ATOM 5623 OG1 THR B 362 18. .979 37. .830 69. .042 1. .00 0. .00 XXXX5623

ATOM 5624 CG2 THR B 362 21. .342 37. .600 68. .621 1. .00 0. .00 XXXX5624

ATOM 5625 N ASN B 363 19. .302 34. .920 71. .591 1. .00 0. .00 XXXX5625

ATOM 5626 CA ASN B 363 18. .384 34. .421 72. .608 1. .00 0. .00 XXXX5626

ATOM 5627 C ASN B 363 17. .522 35. .532 73. .194 1. .00 0. .00 XXXX5627

ATOM 5628 O ASN B 363 16. .513 35. .271 73. .851 1. .00 0. .00 XXXX5628

ATOM 5629 CB ASN B 363 19. .159 33. .713 73. .719 1. .00 0. .00 XXXX5629

ATOM 5630 CG ASN B 363 19. .779 32. .409 73. .255 1. .00 0. .00 XXXX5630

ATOM 5631 OD1 ASN B 363 19. .142 31. .619 72. .557 1. .00 0. .00 XXXX5631

ATOM 5632 ND2 ASN B 363 21. .031 32. .180 73. .636 1. .00 0. .00 XXXX5632

ATOM 5633 N LYS B 364 17. .928 36. .773 72. .950 1. .00 0. .00 XXXX5633

ATOM 5634 CA LYS B 364 17. .171 37. .935 73. .393 1. .00 0. .00 XXXX5634

ATOM 5635 C LYS B 364 17. .221 39. .024 72. .333 1. .00 0. .00 XXXX5635

ATOM 5636 O LYS B 364 18. .056 38. .973 71. .428 1. .00 0. .00 XXXX5636

ATOM 5637 CB LYS B 364 17. .724 38. .479 74. .712 1. .00 0. .00 XXXX5637

ATOM 5638 CG LYS B 364 17. .678 37. .514 75. .881 1. .00 0. .00 XXXX5638

ATOM 5639 CD LYS B 364 18. .339 38. .139 77. .101 1. .00 0. .00 XXXX5639

ATOM 5640 CE LYS B 364 18. .336 37. .199 78. .295 1. .00 0. .00 XXXX5640

ATOM 5641 NZ LYS B 364 19. .027 37. .808 79. .468 1. .00 0. .00 XXXX5641

ATOM 5642 N PRO B 365 16. .324 40. .014 72. .436 1. .00 0. .00 XXXX5642

ATOM 5643 CA PRO B 365 16. .431 41. .187 71. .565 1. .00 0. .00 XXXX5643

ATOM 5644 C PRO B 365 17. .758 41. .905 71. .793 1. .00 0. .00 XXXX5644

ATOM 5645 O PRO B 365 18. .257 41. .920 72. .919 1. .00 0. .00 XXXX5645

ATOM 5646 CB PRO B 365 15. .246 42. .056 71. .996 1. .00 0. .00 XXXX5646

ATOM 5647 CG PRO B 365 14. .268 41. .092 72. .587 1. .00 0. .00 XXXX5647

ATOM 5648 CD PRO B 365 15. .104 40. .042 73. .261 1. .00 0. .00 XXXX5648

ATOM 5649 N VAL B 366 18. .318 42. .491 70. .741 1. .00 0. .00 XXXX5649

ATOM 5650 CA VAL B 366 19. .596 43. .184 70. .846 1. .00 0. .00 XXXX5650

ATOM 5651 C VAL B 366 19. .398 44. .693 70. .854 1. .00 0. .00 XXXX5651

ATOM 5652 O VAL B 366 18. .644 45. .233 70. .043 1. .00 0. .00 XXXX5652

ATOM 5653 CB VAL B 366 20. .538 42. .802 69. .688 1. .00 0. .00 XXXX5653

ATOM 5654 CGI VAL B 366 21. .865 43. .537 69. .816 1. .00 0. .00 XXXX5654

ATOM 5655 CG2 VAL B 366 20. .757 41. .299 69. .660 1. .00 0. .00 XXXX5655

ATOM 5656 N LYS B 367 20. .074 45. .373 71. .775 1. .00 0. .00 XXXX5656

ATOM 5657 CA LYS B 367 20. .037 46. .829 71. .818 1. .00 0. .00 XXXX5657

ATOM 5658 C LYS B 367 20. .637 47. .405 70. .542 1. .00 0. .00 XXXX5658

ATOM 5659 O LYS B 367 21. .728 47. .007 70. .134 1. .00 0. .00 XXXX5659

ATOM 5660 CB LYS B 367 20. .785 47. .360 73. .044 1. .00 0. .00 XXXX5660

ATOM 5661 CG LYS B 367 20. .649 48. .862 73. .247 1. .00 0. .00 XXXX5661

ATOM 5662 CD LYS B 367 21. .406 49. .330 74. .482 1. .00 0. .00 XXXX5662

ATOM 5663 CE LYS B 367 21. .058 50. .770 74. .833 1. .00 0. .00 XXXX5663

ATOM 5664 NZ LYS B 367 21. .396 51. .717 73. .735 1. .00 0. .00 XXXX5664

ATOM 5665 N PRO B 368 19. .925 48. .348 69. .909 1. .00 0. .00 XXXX5665

ATOM 5666 CA PRO B 368 20. .414 48. .981 68. .679 1. .00 0. .00 XXXX5666

ATOM 5667 C PRO B 368 21. .680 49. .801 68. .911 1. .00 0. .00 XXXX5667

ATOM 5668 O PRO B 368 21. .770 50. .544 69. .888 1. .00 0. .00 XXXX5668

ATOM 5669 CB PRO B 368 19. .247 49. .878 68. .257 1. .00 0. .00 XXXX5669

ATOM 5670 CG PRO B 368 18. .490 50. .136 69. .518 1. .00 0. .00 XXXX5670

ATOM 5671 CD PRO B 368 18. .610 48. .873 70. .317 1. .00 0. .00 XXXX5671 Attorney Docket No. 35327-522001 WO

ATOM 5672 N ASP B 369 22. .641 49. .657 68. .004 1. .00 0. .00 XXXX5672

ATOM 5673 CA ASP B 369 23. .944 50. .300 68. .124 1. .00 0. .00 XXXX5673

ATOM 5674 C ASP B 369 24. .378 50. .811 66. .753 1. .00 0. .00 XXXX5674

ATOM 5675 O ASP B 369 25. .296 50. .263 66. .143 1. .00 0. .00 XXXX5675

ATOM 5676 CB ASP B 369 24. .972 49. .318 68. .690 1. .00 0. .00 XXXX5676

ATOM 5677 CG ASP B 369 26. .305 49. .971 68. .997 1. .00 0. .00 XXXX5677

ATOM 5678 OD1 ASP B 369 26. .394 51. .216 68. .939 1. .00 0. .00 XXXX5678

ATOM 5679 OD2 ASP B 369 27. .266 49. .232 69. .295 1. .00 0. .00 XXXX5679

ATOM 5680 N PRO B 370 23. .709 51. .864 66. .264 1. .00 0. .00 XXXX5680

ATOM 5681 CA PRO B 370 23. .890 52. .355 64. .892 1. .00 0. .00 XXXX5681

ATOM 5682 C PRO B 370 25. .311 52. .818 64. .585 1. .00 0. .00 XXXX5682

ATOM 5683 O PRO B 370 25. .739 52. .726 63. .435 1. .00 0. .00 XXXX5683

ATOM 5684 CB PRO B 370 22. .910 53. .532 64. .809 1. .00 0. .00 XXXX5684

ATOM 5685 CG PRO B 370 22. .658 53. .930 66. .227 1. .00 0. .00 XXXX5685

ATOM 5686 CD PRO B 370 22. .711 52. .654 67. .004 1. .00 0. .00 XXXX5686

ATOM 5687 N TYR B 371 26. .029 53. .305 65. .591 1. .00 0. .00 XXXX5687

ATOM 5688 CA TYR B 371 27. .397 53. .764 65. .385 1. .00 0. .00 XXXX5688

ATOM 5689 C TYR B 371 28. .416 52. .706 65. .800 1. .00 0. .00 XXXX5689

ATOM 5690 O TYR B 371 29. .620 52. .963 65. .805 1. .00 0. .00 XXXX5690

ATOM 5691 CB TYR B 371 27. .641 55. .070 66. .143 1. .00 0. .00 XXXX5691

ATOM 5692 CG TYR B 371 26. .967 56. .264 65. .504 1. .00 0. .00 XXXX5692

ATOM 5693 CD1 TYR B 371 25. .713 56. .689 65. .923 1. .00 0. .00 XXXX5693

ATOM 5694 CD2 TYR B 371 27. .580 56. .955 64. .466 1. .00 0. .00 XXXX5694

ATOM 5695 CE1 TYR B 371 25. .094 57. .777 65. .335 1. .00 0. .00 XXXX5695

ATOM 5696 CE2 TYR B 371 26. .969 58. .044 63. .871 1. .00 0. .00 XXXX5696

ATOM 5697 CZ TYR B 371 25. .725 58. .450 64. .310 1. .00 0. .00 XXXX5697

ATOM 5698 OH TYR B 371 25. .111 59. .532 63. .723 1. .00 0. .00 XXXX5698

ATOM 5699 N LEU B 372 27. .923 51. .517 66. .133 1. .00 0. .00 XXXX5699

ATOM 5700 CA LEU B 372 28. .780 50. .382 66. .467 1. .00 0. .00 XXXX5700

ATOM 5701 C LEU B 372 29. .765 50. .712 67. .586 1. .00 0. .00 XXXX5701

ATOM 5702 O LEU B 372 30. .940 50. .352 67. .518 1. .00 0. .00 XXXX5702

ATOM 5703 CB LEU B 372 29. .534 49. .909 65. .224 1. .00 0. .00 XXXX5703

ATOM 5704 CG LEU B 372 28. .644 49. .388 64. .093 1. .00 0. .00 XXXX5704

ATOM 5705 CD1 LEU B 372 29. .480 48. .932 62. .907 1. .00 0. .00 XXXX5705

ATOM 5706 CD2 LEU B 372 27. .749 48. .261 64. .590 1. .00 0. .00 XXXX5706

ATOM 5707 N LYS B 373 29. .272 51. .394 68. .614 1. .00 0. .00 XXXX5707

ATOM 5708 CA LYS B 373 30. .104 51. .803 69. .739 1. .00 0. .00 XXXX5708

ATOM 5709 C LYS B 373 30. .624 50. .597 70. .514 1. .00 0. .00 XXXX5709

ATOM 5710 O LYS B 373 31. .689 50. .652 71. .126 1. .00 0. .00 XXXX5710

ATOM 5711 CB LYS B 373 29. .315 52. .720 70. .675 1. .00 0. .00 XXXX5711

ATOM 5712 CG LYS B 373 28. .883 54. .031 70. .042 1. .00 0. .00 XXXX5712

ATOM 5713 CD LYS B 373 27. .994 54. .827 70. .984 1. .00 0. .00 XXXX5713

ATOM 5714 CE LYS B 373 27. .249 55. .927 70. .246 1. .00 0. .00 XXXX5714

ATOM 5715 NZ LYS B 373 26. .331 56. .676 71. .149 1. .00 0. .00 XXXX5715

ATOM 5716 N GLY B 374 29. .864 49. .506 70. .479 1. .00 0. .00 XXXX5716

ATOM 5717 CA GLY B 374 30. .224 48. .297 71. .198 1. .00 0. .00 XXXX5717

ATOM 5718 C GLY B 374 31. .223 47. .435 70. .452 1. .00 0. .00 XXXX5718

ATOM 5719 O GLY B 374 31. .608 46. .365 70. .925 1. .00 0. .00 XXXX5719

ATOM 5720 N TYR B 375 31. .647 47. .901 69. .283 1. .00 0. .00 XXXX5720

ATOM 5721 CA TYR B 375 32. .574 47. .141 68. .454 1. .00 0. .00 XXXX5721

ATOM 5722 C TYR B 375 33. .906 47. .864 68. .310 1. .00 0. .00 XXXX5722

ATOM 5723 O TYR B 375 34. .023 48. .866 67. .601 1. .00 0. .00 XXXX5723

ATOM 5724 CB TYR B 375 31. .958 46. .858 67. .084 1. .00 0. .00 XXXX5724

ATOM 5725 CG TYR B 375 30. .703 46. .023 67. .178 1. .00 0. .00 XXXX5725

ATOM 5726 CD1 TYR B 375 30. .769 44. .635 67. .171 1. .00 0. .00 XXXX5726

ATOM 5727 CD2 TYR B 375 29. .455 46. .619 67. .295 1. .00 0. .00 XXXX5727

ATOM 5728 CE1 TYR B 375 29. .626 43. .865 67. .266 1. .00 0. .00 XXXX5728

ATOM 5729 CE2 TYR B 375 28. .306 45. .856 67. .391 1. .00 0. .00 XXXX5729

ATOM 5730 CZ TYR B 375 28. .397 44. .481 67. .376 1. .00 0. .00 XXXX5730

ATOM 5731 OH TYR B 375 27. .256 43. .719 67. .471 1. .00 0. .00 XXXX5731

ATOM 5732 N GLU B 376 34. .904 47. .329 69. .003 1. .00 0. .00 XXXX5732

ATOM 5733 CA GLU B 376 36. .227 47. .930 69. .107 1. .00 0. .00 XXXX5733

ATOM 5734 C GLU B 376 36. .892 48. .164 67. .749 1. .00 0. .00 XXXX5734

ATOM 5735 O GLU B 376 37. .684 49. .093 67. .595 1. .00 0. .00 XXXX5735

ATOM 5736 CB GLU B 376 37. .106 47. .034 69. .989 1. .00 0. .00 XXXX5736

ATOM 5737 CG GLU B 376 38. .489 47. .568 70. .297 1. .00 0. .00 XXXX5737

ATOM 5738 CD GLU B 376 39. .505 47. .192 69. .240 1. .00 0. .00 XXXX5738 Attorney Docket No. 35327-522001 WO

ATOM 5739 OE1 GLU B 376 39. .233 46. .260 68. .452 1. .00 0. .00 XXXX5739

ATOM 5740 OE2 GLU B 376 40. .585 47. .815 69. .214 1. .00 0. .00 XXXX5740

ATOM 5741 N TRP B 377 36. .568 47. .322 66. .773 1. .00 0. .00 XXXX5741

ATOM 5742 CA TRP B 377 37. .154 47. .420 65. .437 1. .00 0. .00 XXXX5742

ATOM 5743 C TRP B 377 36. .473 48. .451 64. .529 1. .00 0. .00 XXXX5743

ATOM 5744 O TRP B 377 36. .962 48. .742 63. .438 1. .00 0. .00 XXXX5744

ATOM 5745 CB TRP B 377 37. .119 46. .050 64. .756 1. .00 0. .00 XXXX5745

ATOM 5746 CG TRP B 377 35. .757 45. .424 64. .768 1. .00 0. .00 XXXX5746

ATOM 5747 CD1 TRP B 377 35. .297 44. .479 65. .637 1. .00 0. .00 XXXX5747

ATOM 5748 CD2 TRP B 377 34. .672 45. .713 63. .878 1. .00 0. .00 XXXX5748

ATOM 5749 NE1 TRP B 377 33. .995 44. .156 65. .340 1. .00 0. .00 XXXX5749

ATOM 5750 CE2 TRP B 377 33. .588 44. .901 64. .264 1. .00 0. .00 XXXX5750

ATOM 5751 CE3 TRP B 377 34. .514 46. .578 62. .789 1. .00 0. .00 XXXX5751

ATOM 5752 CZ2 TRP B 377 32. .362 44. .926 63. .601 1. .00 0. .00 XXXX5752

ATOM 5753 CZ3 TRP B 377 33. .296 46. .602 62. .133 1. .00 0. .00 XXXX5753

ATOM 5754 CH2 TRP B 377 32. .236 45. .781 62. .541 1. .00 0. .00 XXXX5754

ATOM 5755 N ALA B 378 35. .349 48. .999 64. .981 1. .00 0. .00 XXXX5755

ATOM 5756 CA ALA B 378 34. .553 49. .918 64. .166 1. .00 0. .00 XXXX5756

ATOM 5757 C ALA B 378 34. .846 51. .388 64. .462 1. .00 0. .00 XXXX5757

ATOM 5758 O ALA B 378 34. .076 52. .269 64. .078 1. .00 0. .00 XXXX5758

ATOM 5759 CB ALA B 378 33. .067 49. .634 64. .362 1. .00 0. .00 XXXX5759

ATOM 5760 N GLN B 379 35. .960 51. .643 65. .141 1. .00 0. .00 XXXX5760

ATOM 5761 CA GLN B 379 36. .297 52. .976 65. .641 1. .00 0. .00 XXXX5761

ATOM 5762 C GLN B 379 36. .161 54. .125 64. .634 1. .00 0. .00 XXXX5762

ATOM 5763 O GLN B 379 35. .499 55. .122 64. .919 1. .00 0. .00 XXXX5763

ATOM 5764 CB GLN B 379 37. .726 52. .965 66. .190 1. .00 0. .00 XXXX5764

ATOM 5765 CG GLN B 379 38. .205 54. .314 66. .694 1. .00 0. .00 XXXX5765

ATOM 5766 CD GLN B 379 37. .477 54. .757 67. .946 1. .00 0. .00 XXXX5766

ATOM 5767 OE1 GLN B 379 37. .310 53. .982 68. .888 1. .00 0. .00 XXXX5767

ATOM 5768 NE2 GLN B 379 37. .041 56. .011 67. .965 1. .00 0. .00 XXXX5768

ATOM 5769 N GLY B 380 36. .778 53. .996 63. .464 1. .00 0. .00 XXXX5769

ATOM 5770 CA GLY B 380 36. .863 55. .119 62. .543 1. .00 0. .00 XXXX5770

ATOM 5771 C GLY B 380 35. .841 55. .183 61. .420 1. .00 0. .00 XXXX5771

ATOM 5772 O GLY B 380 35. .891 56. .089 60. .589 1. .00 0. .00 XXXX5772

ATOM 5773 N LEU B 381 34. .903 54. .241 61. .405 1. .00 0. .00 XXXX5773

ATOM 5774 CA LEU B 381 33. .995 54. .067 60. .271 1. .00 0. .00 XXXX5774

ATOM 5775 C LEU B 381 33. .143 55. .292 59. .914 1. .00 0. .00 XXXX5775

ATOM 5776 O LEU B 381 33. .050 55. .658 58. .742 1. .00 0. .00 XXXX5776

ATOM 5777 CB LEU B 381 33. .075 52. .872 60. .531 1. .00 0. .00 XXXX5777

ATOM 5778 CG LEU B 381 33. .768 51. .508 60. .548 1. .00 0. .00 XXXX5778

ATOM 5779 CD1 LEU B 381 32. .763 50. .391 60. .773 1. .00 0. .00 XXXX5779

ATOM 5780 CD2 LEU B 381 34. .538 51. .289 59. .255 1. .00 0. .00 XXXX5780

ATOM 5781 N SER B 382 32. .520 55. .919 60. .907 1. .00 0. .00 XXXX5781

ATOM 5782 CA SER B 382 31. .584 57. .011 60. .635 1. .00 0. .00 XXXX5782

ATOM 5783 C SER B 382 32. .279 58. .353 60. .404 1. .00 0. .00 XXXX5783

ATOM 5784 O SER B 382 31. .738 59. .226 59. .723 1. .00 0. .00 XXXX5784

ATOM 5785 CB SER B 382 30. .575 57. .148 61. .779 1. .00 0. .00 XXXX5785

ATOM 5786 OG SER B 382 31. .206 57. .579 62. .972 1. .00 0. .00 XXXX5786

ATOM 5787 N GLU B 383 33. .466 58. .513 60. .983 1. .00 0. .00 XXXX5787

ATOM 5788 CA GLU B 383 34. .259 59. .737 60. .842 1. .00 0. .00 XXXX5788

ATOM 5789 C GLU B 383 33. .647 60. .923 61. .587 1. .00 0. .00 XXXX5789

ATOM 5790 O GLU B 383 34. .227 62. .007 61. .621 1. .00 0. .00 XXXX5790

ATOM 5791 CB GLU B 383 34. .436 60. .102 59. .365 1. .00 0. .00 XXXX5791

ATOM 5792 CG GLU B 383 34. .971 58. .980 58. .493 1. .00 0. .00 XXXX5792

ATOM 5793 CD GLU B 383 35. .207 59. .424 57. .062 1. .00 0. .00 XXXX5793

ATOM 5794 OE1 GLU B 383 34. .692 58. .759 56. .138 1. .00 0. .00 XXXX5794

ATOM 5795 OE2 GLU B 383 35. .908 60. .438 56. .862 1. .00 0. .00 XXXX5795

ATOM 5796 N GLN B 384 32. .476 60. .715 62. .181 1. .00 0. .00 XXXX5796

ATOM 5797 CA GLN B 384 31. .789 61. .776 62. .908 1. .00 0. .00 XXXX5797

ATOM 5798 C GLN B 384 32. .336 61. .924 64. .326 1. .00 0. .00 XXXX5798

ATOM 5799 O GLN B 384 32. .753 60. .946 64. .945 1. .00 0. .00 XXXX5799

ATOM 5800 CB GLN B 384 30. .285 61. .504 62. .951 1. .00 0. .00 XXXX5800

ATOM 5801 CG GLN B 384 29. .655 61. .283 61. .585 1. .00 0. .00 XXXX5801

ATOM 5802 CD GLN B 384 28. .210 60. .835 61. .679 1. .00 0. .00 XXXX5802

ATOM 5803 OE1 GLN B 384 27. .510 61. .159 62. .639 1. .00 0. .00 XXXX5803

ATOM 5804 NE2 GLN B 384 27. .758 60. .078 60. .684 1. .00 0. .00 XXXX5804

ATOM 5805 N GLY B 385 32. .332 63. .151 64. .834 1. .00 0. .00 XXXX5805 Attorney Docket No. 35327-522001 WO

ATOM 5806 CA GLY B 385 32. .811 63. .421 66. .177 1. .00 0. .00 XXXX5806

ATOM 5807 C GLY B 385 31. .711 63. .314 67. .215 1. .00 0. .00 XXXX5807

ATOM 5808 O GLY B 385 30. .546 63. .102 66. .879 1. .00 0. .00 XXXX5808

ATOM 5809 N GLY B 386 32. .085 63. .458 68. .482 1. .00 0. .00 XXXX5809

ATOM 5810 CA GLY B 386 31. .128 63. .417 69. .571 1. .00 0. .00 XXXX5810

ATOM 5811 C GLY B 386 30. .850 62. .016 70. .080 1. .00 0. .00 XXXX5811

ATOM 5812 O GLY B 386 31. .479 61. .049 69. .647 1. .00 0. .00 XXXX5812

ATOM 5813 N SER B 387 29. .902 61. .908 71. .005 1. .00 0. .00 XXXX5813

ATOM 5814 CA SER B 387 29. .535 60. .620 71. .583 1. .00 0. .00 XXXX5814

ATOM 5815 C SER B 387 28. .490 59. .911 70. .730 1. .00 0. .00 XXXX5815

ATOM 5816 O SER B 387 28. .114 58. .774 71. .014 1. .00 0. .00 XXXX5816

ATOM 5817 CB SER B 387 29. .009 60. .800 73. .009 1. .00 0. .00 XXXX5817

ATOM 5818 OG SER B 387 27. .770 61. .489 73. .010 1. .00 0. .00 XXXX5818

ATOM 5819 N HIS B 388 28. .024 60. .596 69. .689 1. .00 0. .00 XXXX5819

ATOM 5820 CA HIS B 388 27. .012 60. .052 68. .789 1. .00 0. .00 XXXX5820

ATOM 5821 C HIS B 388 25. .683 59. .850 69. .511 1. .00 0. .00 XXXX5821

ATOM 5822 O HIS B 388 24. .836 59. .075 69. .068 1. .00 0. .00 XXXX5822

ATOM 5823 CB HIS B 388 27. .486 58. .731 68. .179 1. .00 0. .00 XXXX5823

ATOM 5824 CG HIS B 388 28. .818 58. .825 67. .499 1. .00 0. .00 XXXX5824

ATOM 5825 ND1 HIS B 388 29. .821 57. .900 67. .701 1. .00 0. .00 XXXX5825

ATOM 5826 CD2 HIS B 388 29. .308 59. .729 66. .622 1. .00 0. .00 XXXX5826

ATOM 5827 CE1 HIS B 388 30. .874 58. .234 66. .977 1. .00 0. .00 XXXX5827

ATOM 5828 NE2 HIS B 388 30. .591 59. .338 66. .312 1. .00 0. .00 XXXX5828

HETATM 5829 C URE C 314 -18. .440 50. .714 38. .498 1. .00 0. .00 XXXX5829

HETATM 5830 O URE C 314 -18. .679 51. .470 39. .454 1. .00 0. .00 XXXX5830

HETATM 5831 Nl URE C 314 -18. .561 51. .145 37. .184 1. .00 0. .00 XXXX5831

HETATM 5832 N2 URE C 314 -18. .035 49. .401 38. .696 1. .00 0. .00 XXXX5832

HETATM 5833 HN11 URE C 314 -18. .810 51. .953 37. .029 1. .00 0. .00 XXXX5833

HETATM 5834 HN12 URE C 314 -18. .402 50. .644 36. .503 1. .00 0. .00 XXXX5834

HETATM 5835 HN21 URE C 314 -17. .933 49. .049 39. .474 1. .00 0. .00 XXXX5835

HETATM 5836 HN22 URE C 314 -17. .877 48. .904 38. .013 1. .00 0. .00 XXXX5836

HETATM 5837 C URE D 314 18. .546 50. .437 52. .571 1. .00 0. .00 XXXX5837

HETATM 5838 O URE D 314 18. .650 50. .811 53. .750 1. .00 0. .00 XXXX5838

HETATM 5839 Nl URE D 314 18. .906 51. .258 51. .522 1. .00 0. .00 XXXX5839

HETATM 5840 N2 URE D 314 18. .062 49. .175 52. .246 1. .00 0. .00 XXXX5840

HETATM 5841 HN11 URE D 314 18. .822 50. .970 50. .716 1. .00 0. .00 XXXX5841

HETATM 5842 HN12 URE D 314 19. .215 52. .053 51. .627 1. .00 0. .00 XXXX5842

HETATM 5843 HN21 URE D 314 17. .980 48. .892 51. .438 1. .00 0. .00 XXXX5843

HETATM 5844 HN22 URE D 314 17. .829 48. .640 52. .878 1. .00 0. .00 XXXX5844

HETATM 5847 O HOH S 1 15. .599 51. .447 60. .435 1. .00 0. .00 XXXX5847

HETATM 5848 O HOH S 2 16. .822 47. .950 41. .635 1. .00 0. .00 XXXX5848

HETATM 5849 O HOH S 3 -19. .774 42. .426 41. .534 1. .00 0. .00 XXXX5849

HETATM 5850 O HOH S 4 19. .801 42. .459 49. .356 1. .00 0. .00 XXXX5850

HETATM 5851 O HOH S 5 11. .552 38. .612 56. .739 1. .00 0. .00 XXXX5851

HETATM 5852 O HOH S 6 22. .958 57. .697 48. .094 1. .00 0. .00 XXXX5852

HETATM 5853 O HOH S 7 12. .376 41. .064 69. .244 1. .00 0. .00 XXXX5853

HETATM 5854 O HOH S 8 -9. .125 32. .907 34. .381 1. .00 0. .00 XXXX5854

HETATM 5855 O HOH S 9 -15. .412 51. .659 30. .296 1. .00 0. .00 XXXX5855

HETATM 5856 O HOH S 10 -10. .825 44. .146 29. .208 1. .00 0. .00 XXXX5856

HETATM 5857 O HOH S 11 -1. .130 60. .293 46. .232 1. .00 0. .00 XXXX5857

HETATM 5858 O HOH S 12 -16. .497 49. .580 25. .822 1. .00 0. .00 XXXX5858

HETATM 5859 O HOH S 13 -17. .749 59. .470 24. .550 1. .00 0. .00 XXXX5859

HETATM 5860 O HOH S 14 6. .487 32. .324 50. .237 1. .00 0. .00 XXXX5860

HETATM 5861 O HOH S 15 10. .789 43. .913 61. .570 1. .00 0. .00 XXXX5861

HETATM 5862 O HOH S 16 5. .738 45. .168 48. .057 1. .00 0. .00 XXXX5862

HETATM 5863 O HOH S 17 -25. .478 54. .047 22. .495 1. .00 0. .00 XXXX5863

HETATM 5864 O HOH S 18 -22. .693 57. .721 42. .894 1. .00 0. .00 XXXX5864

HETATM 5865 O HOH S 19 -13. .136 46. .328 32. .985 1. .00 0. .00 XXXX5865

HETATM 5866 O HOH S 20 4. .415 59. .326 40. .882 1. .00 0. .00 XXXX5866

HETATM 5867 O HOH S 21 -3. .325 63. .403 25. .127 1. .00 0. .00 XXXX5867

HETATM 5868 O HOH S 22 -11. .478 38. .744 34. .037 1. .00 0. .00 XXXX5868

HETATM 5869 O HOH S 23 20. .036 35. .614 49. .410 1. .00 0. .00 XXXX5869

HETATM 5870 O HOH S 24 -12. .253 41. .166 21. .527 1. .00 0. .00 XXXX5870

HETATM 5871 O HOH s 25 14. .960 44. .898 60. .227 1. .00 0. .00 XXXX5871

HETATM 5872 0 HOH s 26 13. .094 54. .115 48. .871 1. .00 0. .00 XXXX5872

HETATM 5873 0 HOH s 27 -4. .263 59. .144 50. .114 1. .00 0. .00 XXXX5873

HETATM 5874 0 HOH s 28 -14. .866 45. .280 30. .444 1. .00 0. .00 XXXX5874 Attorney Docket No. 35327-522001 WO

HETATM 5875 O HOH S 29 -5. .532 45. .224 42. .682 1. .00 0. .00 XXXX5875

HETATM 5876 O HOH s 30 27. .408 43. .833 49. .206 1. .00 0. .00 XXXX5876

HETATM 5877 O HOH s 31 9. .164 32. .568 56. .320 1. .00 0. .00 XXXX5877

HETATM 5878 O HOH s 32 -34. .064 33. .744 56. .869 1. .00 0. .00 XXXX5878

HETATM 5879 O HOH s 33 14. .644 45. .745 48. .030 1. .00 0. .00 XXXX5879

HETATM 5880 O HOH s 34 21. .154 47. .817 41. .376 1. .00 0. .00 XXXX5880

HETATM 5881 O HOH s 35 9. .477 47. .351 41. .376 1. .00 0. .00 XXXX5881

HETATM 5882 O HOH s 36 22. .145 46. .240 58. .765 1. .00 0. .00 XXXX5882

HETATM 5883 O HOH s 37 -33. .293 42. .556 23. .528 1. .00 0. .00 XXXX5883

HETATM 5884 O HOH s 38 -6. .243 32. .392 40. .338 1. .00 0. .00 XXXX5884

HETATM 5885 O HOH s 39 13. .265 46. .316 57. .730 1. .00 0. .00 XXXX5885

HETATM 5886 O HOH s 40 6. .107 42. .817 45. .440 1. .00 0. .00 XXXX5886

HETATM 5887 O HOH s 41 -19. .895 35. .575 41. .318 1. .00 0. .00 XXXX5887

HETATM 5888 O HOH s 42 -16. .702 47. .902 49. .154 1. .00 0. .00 XXXX5888

HETATM 5889 O HOH s 43 -27. .218 44. .104 41. .714 1. .00 0. .00 XXXX5889

HETATM 5890 O HOH s 44 21. .504 30. .477 42. .296 1. .00 0. .00 XXXX5890

HETATM 5891 O HOH s 45 -32. .709 39. .943 57. .611 1. .00 0. .00 XXXX5891

HETATM 5892 O HOH s 46 16. .551 49. .201 65. .099 1. .00 0. .00 XXXX5892

HETATM 5893 O HOH s 47 36. .313 49. .387 55. .652 1. .00 0. .00 XXXX5893

HETATM 5894 O HOH s 48 25. .379 53. .655 68. .443 1. .00 0. .00 XXXX5894

HETATM 5895 O HOH s 49 -5. .817 50. .835 13. .611 1. .00 0. .00 XXXX5895

HETATM 5896 O HOH s 50 -19. .632 32. .254 48. .999 1. .00 0. .00 XXXX5896

HETATM 5897 O HOH s 51 -9. .878 43. .560 38. .787 1. .00 0. .00 XXXX5897

HETATM 5898 O HOH s 52 -14. .673 45. .621 42. .803 1. .00 0. .00 XXXX5898

HETATM 5899 O HOH s 53 2. .757 40. .806 51. .172 1. .00 0. .00 XXXX5899

HETATM 5900 O HOH s 54 1. .354 60. .487 44. .949 1. .00 0. .00 XXXX5900

HETATM 5901 0 HOH s 55 -21. .953 46. .429 32. .063 1. .00 0. .00 XXXX5901

HETATM 5902 0 HOH s 56 -35. .313 43. .395 49. .077 1. .00 0. .00 XXXX5902

HETATM 5903 0 HOH s 57 7. .570 34. .579 40. .965 1. .00 0. .00 XXXX5903

HETATM 5904 0 HOH s 58 -12. .580 23. .449 40. .063 1. .00 0. .00 XXXX5904

HETATM 5905 0 HOH s 59 -9. .386 58. .413 12. .975 1. .00 0. .00 XXXX5905

HETATM 5906 0 HOH s 60 23. .459 54. .797 70. .144 1. .00 0. .00 XXXX5906

HETATM 5907 0 HOH s 61 24. .113 56. .488 57. .199 1. .00 0. .00 XXXX5907

HETATM 5908 0 HOH s 62 -9. .277 37. .394 52. .561 1. .00 0. .00 XXXX5908

HETATM 5909 0 HOH s 63 34. .319 34. .102 33. .997 1. .00 0. .00 XXXX5909

HETATM 5910 0 HOH s 64 -21. .186 30. .370 48. .298 1. .00 0. .00 XXXX5910

HETATM 5911 0 HOH s 65 -8. .214 34. .115 40. .832 1. .00 0. .00 XXXX5911

HETATM 5912 0 HOH s 66 19. .689 32. .515 41. .556 1. .00 0. .00 XXXX5912

HETATM 5913 0 HOH s 67 35. .562 43. .506 41. .860 1. .00 0. .00 XXXX5913

HETATM 5914 0 HOH s 68 -24. .073 56. .796 33. .893 1. .00 0. .00 XXXX5914

HETATM 5915 0 HOH s 69 17. .978 59. .186 66. .344 1. .00 0. .00 XXXX5915

HETATM 5916 0 HOH s 70 -26. .752 42. .995 55. .262 1. .00 0. .00 XXXX5916

HETATM 5917 0 HOH s 71 6. .893 51. .121 37. .968 1. .00 0. .00 XXXX5917

HETATM 5918 0 HOH s 72 12. .845 53. .568 39. .035 1. .00 0. .00 XXXX5918

HETATM 5919 0 HOH s 73 -12. .928 54. .124 42. .256 1. .00 0. .00 XXXX5919

HETATM 5920 0 HOH s 74 37. .649 39. .933 41. .624 1. .00 0. .00 XXXX5920

HETATM 5921 0 HOH s 75 5. .562 64. .957 61. .936 1. .00 0. .00 XXXX5921

HETATM 5922 0 HOH s 76 33. .826 42. .442 67. .785 1. .00 0. .00 XXXX5922

HETATM 5923 0 HOH s 77 -6. .079 42. .627 45. .453 1. .00 0. .00 XXXX5923

HETATM 5924 0 HOH s 78 11. .526 72. .051 54. .159 1. .00 0. .00 XXXX5924

HETATM 5925 0 HOH s 79 8. .050 45. .066 51. .931 1. .00 0. .00 XXXX5925

HETATM 5926 0 HOH s 80 8. .276 34. .269 49. .863 1. .00 0. .00 XXXX5926

HETATM 5927 0 HOH s 81 -36. .776 42. .319 52. .696 1. .00 0. .00 XXXX5927

HETATM 5928 0 HOH s 82 -5. .944 39. .825 19. .655 1. .00 0. .00 XXXX5928

HETATM 5929 0 HOH s 83 28. .397 56. .774 49. .466 1. .00 0. .00 XXXX5929

HETATM 5930 0 HOH s 84 -9. .500 47. .078 49. .508 1. .00 0. .00 XXXX5930

HETATM 5931 0 HOH s 85 -21. .902 53. .952 49. .034 1. .00 0. .00 XXXX5931

HETATM 5932 0 HOH s 86 -33. .373 39. .966 24. .039 1. .00 0. .00 XXXX5932

HETATM 5933 0 HOH s 87 -35. .546 40. .964 50. .440 1. .00 0. .00 XXXX5933

HETATM 5934 0 HOH s 88 -24. .562 59. .979 32. .413 1. .00 0. .00 XXXX5934

HETATM 5935 0 HOH s 89 7. .358 41. .708 31. .769 1. .00 0. .00 XXXX5935

HETATM 5936 0 HOH s 90 -2. .635 40. .931 39. .679 1. .00 0. .00 XXXX5936

HETATM 5937 0 HOH s 91 -34. .942 38. .154 57. .059 1. .00 0. .00 XXXX5937

HETATM 5938 0 HOH s 92 -5. .578 61. .790 12. .807 1. .00 0. .00 XXXX5938

HETATM 5939 0 HOH s 93 -22. .735 34. .236 57. .651 1. .00 0. .00 XXXX5939

HETATM 5940 0 HOH s 94 5. .117 46. .705 22. .769 1. .00 0. .00 XXXX5940

HETATM 5941 0 HOH s 95 -36. .462 40. .212 21. .666 1. .00 0. .00 XXXX5941 Attorney Docket No. 35327-522001 WO

HETATM 5942 O HOH S 96 -20. .860 46. .835 58. .312 1. .00 0. .00 XXXX5942

HETATM 5943 O HOH s 97 -7. .548 34. .905 49. .770 1. .00 0. .00 XXXX5943

HETATM 5944 O HOH s 98 -12. .584 53. .190 51. .845 1. .00 0. .00 XXXX5944

HETATM 5945 O HOH s 99 1. .995 46. .150 73. .444 1. .00 0. .00 XXXX5945

HETATM 5946 O HOH s 100 -43. .461 36. .260 32. .766 1. .00 0. .00 XXXX5946

HETATM 5947 O HOH s 101 -33. .501 29. .233 52. .200 1. .00 0. .00 XXXX5947

HETATM 5948 O HOH s 102 -7. .270 41. .690 58. .853 1. .00 0. .00 XXXX5948

HETATM 5949 O HOH s 103 6. .680 43. .730 29. .933 1. .00 0. .00 XXXX5949

HETATM 5950 O HOH s 104 2. .247 32. .277 52. .847 1. .00 0. .00 XXXX5950

HETATM 5951 O HOH s 105 21. .928 53. .741 41. .984 1. .00 0. .00 XXXX5951

HETATM 5952 O HOH s 106 9. .472 37. .607 38. .230 1. .00 0. .00 XXXX5952

HETATM 5953 O HOH s 107 -26. .666 43. .141 58. .529 1. .00 0. .00 XXXX5953

HETATM 5954 O HOH s 108 5. .623 30. .252 57. .256 1. .00 0. .00 XXXX5954

HETATM 5955 O HOH s 109 5. .630 50. .617 77. .198 1. .00 0. .00 XXXX5955

HETATM 5956 O HOH s 110 40. .143 36. .867 64. .197 1. .00 0. .00 XXXX5956

HETATM 5957 O HOH s 111 30. .891 28. .205 49. .686 1. .00 0. .00 XXXX5957

HETATM 5958 O HOH s 112 35. .617 41. .029 40. .469 1. .00 0. .00 XXXX5958

HETATM 5959 O HOH s 113 9. .860 30. .281 41. .160 1. .00 0. .00 XXXX5959

HETATM 5960 O HOH s 114 15. .025 53. .511 76. .383 1. .00 0. .00 XXXX5960

HETATM 5961 O HOH s 115 3. .368 63. .090 66. .028 1. .00 0. .00 XXXX5961

HETATM 5962 O HOH s 116 9. .352 58. .004 77. .905 1. .00 0. .00 XXXX5962

HETATM 5963 0 HOH s 117 7. .817 56. .588 38. .641 1. .00 0. .00 XXXX5963

HETATM 5964 0 HOH s 118 -25. .957 36. .106 26. .475 1. .00 0. .00 XXXX5964

HETATM 5965 0 HOH s 119 9. .855 43. .319 52. .016 1. .00 0. .00 XXXX5965

HETATM 5966 0 HOH s 120 5. .054 67. .135 37. .718 1. .00 0. .00 XXXX5966

HETATM 5967 0 HOH s 121 -31. .338 48. .463 50. .394 1. .00 0. .00 XXXX5967

HETATM 5968 0 HOH s 122 -36. .127 49. .806 35. .354 1. .00 0. .00 XXXX5968

HETATM 5969 0 HOH s 123 3. .346 64. .953 77. .083 1. .00 0. .00 XXXX5969

HETATM 5970 0 HOH s 124 33. .011 40. .393 33. .311 1. .00 0. .00 XXXX5970

HETATM 5971 0 HOH s 125 22. .444 61. .801 62. .628 1. .00 0. .00 XXXX5971

HETATM 5972 0 HOH s 126 -5. .619 30. .509 33. .293 1. .00 0. .00 XXXX5972

HETATM 5973 0 HOH s 127 33. .470 29. .477 38. .857 1. .00 0. .00 XXXX5973

HETATM 5974 0 HOH s 128 -12. .066 38. .500 55. .690 1. .00 0. .00 XXXX5974

HETATM 5975 0 HOH s 129 39. .613 42. .390 52. .293 1. .00 0. .00 XXXX5975

HETATM 5976 0 HOH s 130 38. .817 31. .392 38. .021 1. .00 0. .00 XXXX5976

HETATM 5977 0 HOH s 131 5. .909 39. .613 71. .255 1. .00 0. .00 XXXX5977

HETATM 5978 0 HOH s 132 26. .773 56. .856 47. .633 1. .00 0. .00 XXXX5978

HETATM 5979 0 HOH s 133 24. .662 59. .899 58. .991 1. .00 0. .00 XXXX5979

HETATM 5980 0 HOH s 134 43. .272 35. .673 58. .079 1. .00 0. .00 XXXX5980

HETATM 5981 0 HOH s 135 31. .436 48. .859 40. .673 1. .00 0. .00 XXXX5981

HETATM 5982 0 HOH s 136 -22. .067 59. .556 41. .107 1. .00 0. .00 XXXX5982

HETATM 5983 0 HOH s 137 0. .664 54. .347 74. .797 1. .00 0. .00 XXXX5983

HETATM 5984 0 HOH s 138 38. .063 51. .588 69. .825 1. .00 0. .00 XXXX5984

HETATM 5985 0 HOH s 139 36. .840 42. .244 38. .288 1. .00 0. .00 XXXX5985

HETATM 5986 0 HOH s 140 11. .016 41. .378 35. .589 1. .00 0. .00 XXXX5986

HETATM 5987 0 HOH s 141 12. .217 38. .875 34. .997 1. .00 0. .00 XXXX5987

HETATM 5988 0 HOH s 142 -10. .825 41. .131 55. .158 1. .00 0. .00 XXXX5988

HETATM 5989 0 HOH s 143 -2. .175 32. .196 37. .648 1. .00 0. .00 XXXX5989

HETATM 5990 0 HOH s 144 5. .628 61. .532 78. .210 1. .00 0. .00 XXXX5990

HETATM 5991 0 HOH s 145 -23. .285 36. .747 58. .139 1. .00 0. .00 XXXX5991

HETATM 5992 0 HOH s 146 27. .561 51. .781 39. .362 1. .00 0. .00 XXXX5992

HETATM 5993 0 HOH s 147 -11. .395 72. .176 37. .125 1. .00 0. .00 XXXX5993

HETATM 5994 0 HOH s 148 25. .356 44. .616 69. .482 1. .00 0. .00 XXXX5994

HETATM 5995 0 HOH s 149 -38. .927 31. .217 52. .753 1. .00 0. .00 XXXX5995

HETATM 5996 0 HOH s 150 -3. .242 65. .528 14. .125 1. .00 0. .00 XXXX5996

HETATM 5997 0 HOH s 151 -16. .321 38. .410 57. .163 1. .00 0. .00 XXXX5997

HETATM 5998 0 HOH s 152 -5. .689 64. .153 14. .372 1. .00 0. .00 XXXX5998

HETATM 5999 0 HOH s 153 -31. .000 28. .254 40. .987 1. .00 0. .00 XXXX5999

HETATM 6000 0 HOH s 154 -7. .422 56. .293 52. .351 1. .00 0. .00 XXXX6000

HETATM 6001 0 HOH s 155 -21. .914 61. .769 28. .582 1. .00 0. .00 XXXX6001

HETATM 6002 0 HOH s 156 -6. .873 51. .155 53. .070 1. .00 0. .00 XXXX6002

HETATM 6003 0 HOH s 157 22. .835 34. .456 33. .045 1. .00 0. .00 XXXX6003

HETATM 6004 0 HOH s 158 -6. .570 43. .711 60. .750 1. .00 0. .00 XXXX6004

HETATM 6005 0 HOH s 159 -32. .060 30. .329 59. .023 1. .00 0. .00 XXXX6005

HETATM 6006 0 HOH s 160 28. .569 39. .745 65. .505 1. .00 0. .00 XXXX6006

HETATM 6007 0 HOH s 161 32. .086 33. .291 32. .651 1. .00 0. .00 XXXX6007

HETATM 6008 0 HOH s 162 12. .277 22. .808 44. .153 1. .00 0. .00 XXXX6008 Attorney Docket No. 35327-522001 WO

HETATM 6009 O HOH S 163 22. .907 57. .349 68. .308 1. .00 0. .00 XXXX6009

HETATM 6010 O HOH s 164 -26. .733 47. .407 20. .389 1. .00 0. .00 XXXX6010

HETATM 6011 O HOH s 165 -1. .729 47. .097 47. .622 1. .00 0. .00 XXXX6011

HETATM 6012 O HOH s 166 35. .256 38. .804 33. .908 1. .00 0. .00 XXXX6012

HETATM 6013 O HOH s 167 -27. .004 22. .089 46. .084 1. .00 0. .00 XXXX6013

HETATM 6014 O HOH s 168 8. .626 61. .161 38. .570 1. .00 0. .00 XXXX6014

HETATM 6015 O HOH s 169 -38. .029 29. .949 38. .833 1. .00 0. .00 XXXX6015

HETATM 6016 O HOH s 170 10. .200 30. .505 65. .411 1. .00 0. .00 XXXX6016

HETATM 6017 O HOH s 171 3. .850 32. .008 50. .524 1. .00 0. .00 XXXX6017

HETATM 6018 O HOH s 172 -5. .416 65. .276 29. .312 1. .00 0. .00 XXXX6018

HETATM 6019 O HOH s 173 -27. .411 41. .746 23. .627 1. .00 0. .00 XXXX6019

HETATM 6020 O HOH s 174 -6. .957 70. .289 22. .134 1. .00 0. .00 XXXX6020

HETATM 6021 O HOH s 175 -16. .267 25. .337 39. .422 1. .00 0. .00 XXXX6021

HETATM 6022 O HOH s 176 10. .025 27. .580 57. .945 1. .00 0. .00 XXXX6022

HETATM 6023 O HOH s 177 2. .808 61. .949 42. .634 1. .00 0. .00 XXXX6023

HETATM 6024 O HOH s 178 35. .908 39. .396 69. .249 1. .00 0. .00 XXXX6024

HETATM 6025 O HOH s 179 -37. .499 39. .738 49. .111 1. .00 0. .00 XXXX6025

HETATM 6026 O HOH s 180 27. .562 41. .357 67. .265 1. .00 0. .00 XXXX6026

HETATM 6027 O HOH s 181 -2. .690 38. .389 41. .980 1. .00 0. .00 XXXX6027

HETATM 6028 O HOH s 182 19. .242 68. .254 58. .574 1. .00 0. .00 XXXX6028

HETATM 6029 O HOH s 183 -3. .266 49. .520 14. .311 1. .00 0. .00 XXXX6029

HETATM 6030 O HOH s 184 -24. .553 41. .347 23. .501 1. .00 0. .00 XXXX6030

HETATM 6031 O HOH s 185 -41. .942 38. .598 27. .621 1. .00 0. .00 XXXX6031

HETATM 6032 O HOH s 186 13. .437 63. .904 40. .255 1. .00 0. .00 XXXX6032

HETATM 6033 0 HOH s 187 13. .159 59. .507 71. .791 1. .00 0. .00 XXXX6033

HETATM 6034 0 HOH s 188 38. .006 29. .900 51. .954 1. .00 0. .00 XXXX6034

HETATM 6035 0 HOH s 189 7. .875 45. .611 40. .159 1. .00 0. .00 XXXX6035

HETATM 6036 0 HOH s 190 -5. .896 39. .780 45. .006 1. .00 0. .00 XXXX6036

HETATM 6037 0 HOH s 191 32. .085 30. .631 31. .973 1. .00 0. .00 XXXX6037

HETATM 6038 0 HOH s 192 15. .135 35. .053 70. .933 1. .00 0. .00 XXXX6038

HETATM 6039 0 HOH s 193 -2. .278 61. .945 48. .452 1. .00 0. .00 XXXX6039

HETATM 6040 0 HOH s 194 -23. .659 45. .746 61. .583 1. .00 0. .00 XXXX6040

HETATM 6041 0 HOH s 195 9. .646 33. .940 38. .761 1. .00 0. .00 XXXX6041

HETATM 6042 0 HOH s 196 14. .503 43. .582 36. .956 1. .00 0. .00 XXXX6042

HETATM 6043 0 HOH s 197 -25. .329 44. .805 21. .403 1. .00 0. .00 XXXX6043

HETATM 6044 0 HOH s 198 -14. .670 48. .499 67. .349 1. .00 0. .00 XXXX6044

HETATM 6045 0 HOH s 199 -43. .566 38. .801 29. .321 1. .00 0. .00 XXXX6045

HETATM 6046 0 HOH s 200 5. .815 54. .498 78. .890 1. .00 0. .00 XXXX6046

HETATM 6047 0 HOH s 201 3. .531 65. .762 41. .611 1. .00 0. .00 XXXX6047

HETATM 6048 0 HOH s 202 23. .391 37. .516 32. .599 1. .00 0. .00 XXXX6048

HETATM 6049 0 HOH s 203 7. .745 51. .736 79. .097 1. .00 0. .00 XXXX6049

HETATM 6050 0 HOH s 204 20. .986 47. .331 32. .755 1. .00 0. .00 XXXX6050

HETATM 6051 0 HOH s 205 6. .586 69. .980 48. .328 1. .00 0. .00 XXXX6051

HETATM 6052 0 HOH s 206 -35. .244 31. .640 55. .891 1. .00 0. .00 XXXX6052

HETATM 6053 0 HOH s 207 -9. .483 45. .381 52. .770 1. .00 0. .00 XXXX6053

HETATM 6054 0 HOH s 208 -28. .373 45. .137 54. .641 1. .00 0. .00 XXXX6054

HETATM 6055 0 HOH s 209 26. .546 46. .859 70. .482 1. .00 0. .00 XXXX6055

HETATM 6056 0 HOH s 210 36. .032 44. .776 38. .157 1. .00 0. .00 XXXX6056

HETATM 6057 0 HOH s 211 -16. .189 66. .748 40. .482 1. .00 0. .00 XXXX6057

HETATM 6058 0 HOH s 212 -28. .885 40. .395 25. .199 1. .00 0. .00 XXXX6058

HETATM 6059 0 HOH s 213 5. .531 63. .679 76. .449 1. .00 0. .00 XXXX6059

HETATM 6060 0 HOH s 214 38. .689 48. .020 56. .301 1. .00 0. .00 XXXX6060

HETATM 6061 0 HOH s 215 -17. .537 42. .717 15. .292 1. .00 0. .00 XXXX6061

HETATM 6062 0 HOH s 216 26. .362 58. .040 56. .064 1. .00 0. .00 XXXX6062

HETATM 6063 0 HOH s 217 22. .273 59. .508 49. .958 1. .00 0. .00 XXXX6063

HETATM 6064 0 HOH s 218 -26. .793 56. .793 43. .505 1. .00 0. .00 XXXX6064

HETATM 6065 0 HOH s 219 43. .685 38. .572 61. .401 1. .00 0. .00 XXXX6065

HETATM 6066 0 HOH s 220 -6. .565 52. .263 56. .790 1. .00 0. .00 XXXX6066

HETATM 6067 0 HOH s 221 17. .518 42. .613 75. .403 1. .00 0. .00 XXXX6067

HETATM 6068 0 HOH s 222 -27. .062 37. .614 24. .540 1. .00 0. .00 XXXX6068

HETATM 6069 0 HOH s 223 21. .641 43. .990 73. .819 1. .00 0. .00 XXXX6069

HETATM 6070 0 HOH s 224 -3. .577 30. .623 21. .396 1. .00 0. .00 XXXX6070

HETATM 6071 0 HOH s 225 -15. .145 53. .918 14. .458 1. .00 0. .00 XXXX6071

HETATM 6072 0 HOH s 226 6. .855 26. .575 54. .995 1. .00 0. .00 XXXX6072

HETATM 6073 0 HOH s 227 33. .842 29. .441 34. .342 1. .00 0. .00 XXXX6073

HETATM 6074 0 HOH s 228 -40. .507 33. .136 33. .419 1. .00 0. .00 XXXX6074

HETATM 6075 0 HOH s 229 14. .086 42. .030 35. .081 1. .00 0. .00 XXXX6075 Attorney Docket No. 35327-522001 WO

HETATM 6076 O HOH S 230 -10. .384 42. .714 52. .971 1. .00 0. .00 XXXX6076

HETATM 6077 O HOH s 231 -28. .143 56. .857 41. .609 1. .00 0. .00 XXXX6077

HETATM 6078 O HOH s 232 -25. .427 38. .985 23. .035 1. .00 0. .00 XXXX6078

HETATM 6079 O HOH s 233 -23. .376 55. .395 20. .918 1. .00 0. .00 XXXX6079

HETATM 6080 O HOH s 234 -39. .660 42. .739 38. .922 1. .00 0. .00 XXXX6080

HETATM 6081 O HOH s 235 3. .001 38. .373 48. .607 1. .00 0. .00 XXXX6081

HETATM 6082 O HOH s 236 -11. .501 30. .529 28. .989 1. .00 0. .00 XXXX6082

HETATM 6083 O HOH s 237 9. .592 42. .593 33. .323 1. .00 0. .00 XXXX6083

HETATM 6084 O HOH s 238 23. .473 50. .969 71. .802 1. .00 0. .00 XXXX6084

HETATM 6085 O HOH s 239 6. .860 52. .951 21. .240 1. .00 0. .00 XXXX6085

HETATM 6086 O HOH s 240 -21. .915 44. .465 17. .216 1. .00 0. .00 XXXX6086

HETATM 6087 O HOH s 241 -3. .574 31. .769 40. .172 1. .00 0. .00 XXXX6087

HETATM 6088 O HOH s 242 19. .204 69. .680 62. .340 1. .00 0. .00 XXXX6088

HETATM 6089 O HOH s 243 42. .035 39. .869 56. .540 1. .00 0. .00 XXXX6089

HETATM 6090 O HOH s 244 2. .607 47. .698 42. .767 1. .00 0. .00 XXXX6090

HETATM 6091 O HOH s 245 -8. .957 24. .390 39. .598 1. .00 0. .00 XXXX6091

HETATM 6092 O HOH s 246 -19. .564 61. .419 41. .906 1. .00 0. .00 XXXX6092

HETATM 6093 O HOH s 247 12. .245 31. .885 66. .604 1. .00 0. .00 XXXX6093

HETATM 6094 O HOH s 248 -23. .266 28. .825 40. .383 1. .00 0. .00 XXXX6094

HETATM 6095 O HOH s 249 16. .525 66. .480 50. .658 1. .00 0. .00 XXXX6095

HETATM 6096 O HOH s 250 -3. .935 66. .710 49. .250 1. .00 0. .00 XXXX6096

HETATM 6097 O HOH s 251 -0. .835 68. .172 25. .966 1. .00 0. .00 XXXX6097

HETATM 6098 O HOH s 252 -11. .398 66. .340 18. .295 1. .00 0. .00 XXXX6098

HETATM 6099 O HOH s 253 -28. .668 32. .295 25. .475 1. .00 0. .00 XXXX6099

HETATM 6100 0 HOH s 254 -26. .530 34. .486 59. .354 1. .00 0. .00 XXXX6100

HETATM 6101 0 HOH s 255 4. .371 69. .174 66. .368 1. .00 0. .00 XXXX6101

HETATM 6102 0 HOH s 256 38. .078 38. .304 65. .536 1. .00 0. .00 XXXX6102

HETATM 6103 0 HOH s 257 -11. .276 35. .937 21. .160 1. .00 0. .00 XXXX6103

HETATM 6104 0 HOH s 258 -24. .139 47. .491 19. .350 1. .00 0. .00 XXXX6104

HETATM 6105 0 HOH s 259 -22. .304 35. .606 18. .727 1. .00 0. .00 XXXX6105

HETATM 6106 0 HOH s 260 6. .403 40. .060 45. .344 1. .00 0. .00 XXXX6106

HETATM 6107 0 HOH s 261 8. .398 49. .044 37. .424 1. .00 0. .00 XXXX6107

HETATM 6108 0 HOH s 262 -21. .523 65. .918 26. .334 1. .00 0. .00 XXXX6108

HETATM 6109 0 HOH s 263 -23. .122 57. .551 22. .614 1. .00 0. .00 XXXX6109

HETATM 6110 0 HOH s 264 28. .570 32. .147 64. .954 1. .00 0. .00 XXXX6110

HETATM 6111 0 HOH s 265 -30. .754 44. .243 54. .051 1. .00 0. .00 XXXX6111

HETATM 6112 0 HOH s 266 19. .822 47. .217 77. .280 1. .00 0. .00 XXXX6112

HETATM 6113 0 HOH s 267 9. .536 45. .774 38. .013 1. .00 0. .00 XXXX6113

HETATM 6114 0 HOH s 268 -13. .104 64. .011 50. .838 1. .00 0. .00 XXXX6114

HETATM 6115 0 HOH s 269 41. .565 49. .185 71. .432 1. .00 0. .00 XXXX6115

HETATM 6116 0 HOH s 270 11. .846 31. .549 63. .410 1. .00 0. .00 XXXX6116

HETATM 6117 0 HOH s 271 -10. .354 30. .778 25. .234 1. .00 0. .00 XXXX6117

HETATM 6118 0 HOH s 272 4. .516 35. .523 43. .014 1. .00 0. .00 XXXX6118

HETATM 6119 0 HOH s 273 -4. .729 38. .677 47. .116 1. .00 0. .00 XXXX6119

HETATM 6120 0 HOH s 274 14. .888 39. .456 35. .003 1. .00 0. .00 XXXX6120

HETATM 6121 0 HOH s 275 -2. .078 32. .445 58. .660 1. .00 0. .00 XXXX6121

HETATM 6122 0 HOH s 276 20. .563 22. .789 59. .030 1. .00 0. .00 XXXX6122

HETATM 6123 0 HOH s 277 20. .934 63. .940 61. .759 1. .00 0. .00 XXXX6123

HETATM 6124 0 HOH s 278 -7. .929 45. .181 38. .901 1. .00 0. .00 XXXX6124

HETATM 6125 0 HOH s 279 -3. .725 60. .475 76. .271 1. .00 0. .00 XXXX6125

HETATM 6126 0 HOH s 280 -2. .033 46. .374 17. .317 1. .00 0. .00 XXXX6126

HETATM 6127 0 HOH s 281 4. .318 60. .597 15. .113 1. .00 0. .00 XXXX6127

HETATM 6128 0 HOH s 282 34. .674 50. .553 51. .257 1. .00 0. .00 XXXX6128

HETATM 6129 0 HOH s 283 -23. .984 55. .757 18. .609 1. .00 0. .00 XXXX6129

HETATM 6130 0 HOH s 284 -7. .297 52. .459 69. .524 1. .00 0. .00 XXXX6130

HETATM 6131 0 HOH s 285 -31. .470 55. .132 39. .573 1. .00 0. .00 XXXX6131

HETATM 6132 0 HOH s 286 -36. .131 27. .278 35. .041 1. .00 0. .00 XXXX6132

HETATM 6133 0 HOH s 287 -6. .437 46. .459 59. .392 1. .00 0. .00 XXXX6133

HETATM 6134 0 HOH s 288 -32. .003 32. .879 58. .472 1. .00 0. .00 XXXX6134

HETATM 6135 0 HOH s 289 -19. .329 54. .096 51. .947 1. .00 0. .00 XXXX6135

HETATM 6136 0 HOH s 290 -12. .806 44. .654 17. .113 1. .00 0. .00 XXXX6136

HETATM 6137 0 HOH s 291 39. .474 48. .489 58. .884 1. .00 0. .00 XXXX6137

HETATM 6138 0 HOH s 292 3. .261 49. .135 76. .659 1. .00 0. .00 XXXX6138

HETATM 6139 0 HOH s 293 -6. .690 26. .859 35. .573 1. .00 0. .00 XXXX6139

HETATM 6140 0 HOH s 294 24. .317 46. .253 29. .348 1. .00 0. .00 XXXX6140

HETATM 6141 0 HOH s 295 2. .725 31. .354 57. .741 1. .00 0. .00 XXXX6141

HETATM 6142 0 HOH s 296 -9. .603 42. .155 57. .320 1. .00 0. .00 XXXX6142 Attorney Docket No. 35327-522001 WO

HETATM 6143 O HOH S 297 2. .755 68. .633 60. .118 1. .00 0. .00 XXXX6143

HETATM 6144 O HOH s 298 -5. .771 50. .383 69. .099 1. .00 0. .00 XXXX6144

HETATM 6145 O HOH s 299 36. .244 37. .722 67. .565 1. .00 0. .00 XXXX6145

HETATM 6146 O HOH s 300 35. .377 31. .833 34. .686 1. .00 0. .00 XXXX6146

HETATM 6147 O HOH s 301 16. .695 39. .121 33. .599 1. .00 0. .00 XXXX6147

HETATM 6148 O HOH s 302 33. .108 39. .647 66. .961 1. .00 0. .00 XXXX6148

HETATM 6149 O HOH s 303 -30. .848 29. .785 49. .974 1. .00 0. .00 XXXX6149

HETATM 6150 O HOH s 304 6. .087 34. .715 33. .188 1. .00 0. .00 XXXX6150

HETATM 6151 O HOH s 305 -13. .093 60. .123 19. .102 1. .00 0. .00 XXXX6151

HETATM 6152 O HOH s 306 -26. .156 45. .622 57. .634 1. .00 0. .00 XXXX6152

HETATM 6153 O HOH s 307 24. .100 46. .925 71. .508 1. .00 0. .00 XXXX6153

HETATM 6154 O HOH s 308 -37. .745 43. .324 45. .347 1. .00 0. .00 XXXX6154

HETATM 6155 O HOH s 309 -3. .996 66. .349 61. .185 1. .00 0. .00 XXXX6155

HETATM 6156 O HOH s 310 -21. .554 58. .037 45. .356 1. .00 0. .00 XXXX6156

HETATM 6157 O HOH s 311 11. .342 65. .909 72. .718 1. .00 0. .00 XXXX6157

HETATM 6158 O HOH s 312 32. .387 28. .532 36. .678 1. .00 0. .00 XXXX6158

HETATM 6159 O HOH s 313 -5. .923 49. .633 51. .789 1. .00 0. .00 XXXX6159

HETATM 6160 O HOH s 314 6. .098 49. .559 39. .266 1. .00 0. .00 XXXX6160

HETATM 6161 O HOH s 315 -9. .672 57. .207 71. .148 1. .00 0. .00 XXXX6161

HETATM 6162 O HOH s 316 7. .722 43. .483 41. .215 1. .00 0. .00 XXXX6162

HETATM 6163 O HOH s 317 -19. .956 25. .576 45. .832 1. .00 0. .00 XXXX6163

HETATM 6164 O HOH s 318 6. .686 70. .061 69. .009 1. .00 0. .00 XXXX6164

HETATM 6165 O HOH s 319 -20. .203 34. .493 59. .056 1. .00 0. .00 XXXX6165

HETATM 6166 O HOH s 320 2. .670 67. .324 21. .006 1. .00 0. .00 XXXX6166

HETATM 6167 0 HOH s 321 -21. .077 26. .567 38. .602 1. .00 0. .00 XXXX6167

HETATM 6168 0 HOH s 322 37. .343 44. .770 43. .285 1. .00 0. .00 XXXX6168

HETATM 6169 0 HOH s 323 22. .290 34. .976 71. .909 1. .00 0. .00 XXXX6169

HETATM 6170 0 HOH s 324 -33. .383 27. .458 38. .895 1. .00 0. .00 XXXX6170

HETATM 6171 0 HOH s 325 26. .215 36. .063 64. .141 1. .00 0. .00 XXXX6171

HETATM 6172 0 HOH s 326 -38. .244 45. .395 21. .480 1. .00 0. .00 XXXX6172

HETATM 6173 0 HOH s 327 -33. .823 29. .410 56. .485 1. .00 0. .00 XXXX6173

HETATM 6174 0 HOH s 328 0. .111 40. .290 23. .975 1. .00 0. .00 XXXX6174

HETATM 6175 0 HOH s 329 33. .065 51. .099 48. .143 1. .00 0. .00 XXXX6175

HETATM 6176 0 HOH s 330 27. .418 56. .317 44. .578 1. .00 0. .00 XXXX6176

HETATM 6177 0 HOH s 331 -23. .559 32. .319 59. .706 1. .00 0. .00 XXXX6177

HETATM 6178 0 HOH s 332 6. .944 52. .861 58. .112 1. .00 0. .00 XXXX6178

HETATM 6179 0 HOH s 333 30. .625 44. .460 36. .827 1. .00 0. .00 XXXX6179

HETATM 6180 0 HOH s 334 -7. .843 45. .731 50. .678 1. .00 0. .00 XXXX6180

HETATM 6181 0 HOH s 335 19. .793 54. .330 38. .932 1. .00 0. .00 XXXX6181

HETATM 6182 0 HOH s 336 -8. .645 61. .062 52. .625 1. .00 0. .00 XXXX6182

HETATM 6183 0 HOH s 337 -41. .146 49. .175 19. .163 1. .00 0. .00 XXXX6183

HETATM 6184 0 HOH s 338 -34. .177 42. .368 58. .283 1. .00 0. .00 XXXX6184

HETATM 6185 0 HOH s 339 -38. .777 44. .807 40. .693 1. .00 0. .00 XXXX6185

HETATM 6186 0 HOH s 340 37. .385 45. .609 47. .079 1. .00 0. .00 XXXX6186

HETATM 6187 0 HOH s 341 18. .577 60. .321 68. .890 1. .00 0. .00 XXXX6187

HETATM 6188 0 HOH s 342 -7. .847 35. .211 53. .749 1. .00 0. .00 XXXX6188

HETATM 6189 0 HOH s 343 -27. .302 52. .189 54. .314 1. .00 0. .00 XXXX6189

HETATM 6190 0 HOH s 344 -32. .140 28. .645 26. .344 1. .00 0. .00 XXXX6190

HETATM 6191 0 HOH s 345 -1. .867 32. .514 42. .154 1. .00 0. .00 XXXX6191

HETATM 6192 0 HOH s 346 -4. .473 69. .524 24. .592 1. .00 0. .00 XXXX6192

HETATM 6193 0 HOH s 347 7. .093 66. .946 26. .396 1. .00 0. .00 XXXX6193

HETATM 6194 0 HOH s 348 -28. .714 26. .214 37. .983 1. .00 0. .00 XXXX6194

HETATM 6195 0 HOH s 349 -14. .762 31. .939 56. .657 1. .00 0. .00 XXXX6195

HETATM 6196 0 HOH s 350 -2. .794 66. .337 69. .987 1. .00 0. .00 XXXX6196

HETATM 6197 0 HOH s 351 -37. .211 45. .652 43. .618 1. .00 0. .00 XXXX6197

HETATM 6198 0 HOH s 352 9. .100 24. .724 50. .684 1. .00 0. .00 XXXX6198

HETATM 6199 0 HOH s 353 -9. .561 57. .774 55. .842 1. .00 0. .00 XXXX6199

HETATM 6200 0 HOH s 354 -9. .876 62. .383 10. .673 1. .00 0. .00 XXXX6200

HETATM 6201 0 HOH s 355 -20. .103 47. .660 13. .611 1. .00 0. .00 XXXX6201

HETATM 6202 0 HOH s 356 3. .387 31. .873 60. .372 1. .00 0. .00 XXXX6202

HETATM 6203 0 HOH s 357 22. .030 50. .920 34. .917 1. .00 0. .00 XXXX6203

HETATM 6204 0 HOH s 358 -19. .209 51. .656 54. .927 1. .00 0. .00 XXXX6204

HETATM 6205 0 HOH s 359 0. .499 30. .783 33. .133 1. .00 0. .00 XXXX6205

HETATM 6206 0 HOH s 360 -39. .370 31. .697 31. .386 1. .00 0. .00 XXXX6206

HETATM 6207 0 HOH s 361 5. .117 62. .172 41. .308 1. .00 0. .00 XXXX6207

HETATM 6208 0 HOH s 362 -12. .901 64. .435 16. .832 1. .00 0. .00 XXXX6208

HETATM 6209 0 HOH s 363 7. .426 27. .841 62. .038 1. .00 0. .00 XXXX6209 Attorney Docket No. 35327-522001 WO

HETATM 6210 O HOH S 364 17. .459 19. .522 61. .126 1. .00 0. .00 XXXX6210

HETATM 6211 O HOH s 365 -39. .602 48. .819 32. .332 1. .00 0. .00 XXXX6211

HETATM 6212 O HOH s 366 -38. .847 43. .709 36. .476 1. .00 0. .00 XXXX6212

HETATM 6213 O HOH s 367 8. .827 54. .531 36. .659 1. .00 0. .00 XXXX6213

HETATM 6214 O HOH s 368 37. .874 43. .258 45. .778 1. .00 0. .00 XXXX6214

HETATM 6215 O HOH s 369 16. .712 66. .501 70. .161 1. .00 0. .00 XXXX6215

HETATM 6216 O HOH s 370 39. .089 31. .143 59. .397 1. .00 0. .00 XXXX6216

HETATM 6217 O HOH s 371 -4. .609 35. .442 47. .602 1. .00 0. .00 XXXX6217

HETATM 6218 O HOH s 372 24. .068 32. .914 31. .102 1. .00 0. .00 XXXX6218

HETATM 6219 O HOH s 373 -10. .884 60. .067 11. .576 1. .00 0. .00 XXXX6219

HETATM 6220 O HOH s 374 14. .009 43. .394 75. .463 1. .00 0. .00 XXXX6220

HETATM 6221 O HOH s 375 -7. .477 43. .627 49. .496 1. .00 0. .00 XXXX6221

HETATM 6222 O HOH s 376 25. .160 38. .222 67. .973 1. .00 0. .00 XXXX6222

HETATM 6223 O HOH s 377 -32. .382 29. .783 48. .554 1. .00 0. .00 XXXX6223

HETATM 6224 O HOH s 378 -38. .008 31. .329 55. .401 1. .00 0. .00 XXXX6224

HETATM 6225 O HOH s 379 -39. .702 42. .449 44. .281 1. .00 0. .00 XXXX6225

HETATM 6226 O HOH s 380 -10. .463 27. .666 32. .788 1. .00 0. .00 XXXX6226

HETATM 6227 O HOH s 381 15. .362 62. .794 72. .976 1. .00 0. .00 XXXX6227

HETATM 6228 O HOH s 382 -16. .784 54. .371 53. .080 1. .00 0. .00 XXXX6228

HETATM 6229 O HOH s 383 -10. .679 26. .903 46. .365 1. .00 0. .00 XXXX6229

HETATM 6230 O HOH s 384 2. .327 42. .399 47. .564 1. .00 0. .00 XXXX6230

HETATM 6231 O HOH s 385 -14. .592 39. .364 55. .829 1. .00 0. .00 XXXX6231

HETATM 6232 O HOH s 386 -0. .292 70. .387 18. .484 1. .00 0. .00 XXXX6232

HETATM 6233 O HOH s 387 -6. .386 66. .899 64. .643 1. .00 0. .00 XXXX6233

HETATM 6234 O HOH s 388 -32. .870 52. .321 43. .132 1. .00 0. .00 XXXX6234

HETATM 6235 O HOH s 389 -8. .242 54. .424 54. .090 1. .00 0. .00 XXXX6235

HETATM 6236 O HOH s 390 17. .878 23. .926 49. .733 1. .00 0. .00 XXXX6236

HETATM 6237 0 HOH s 391 9. .460 62. .534 80. .829 1. .00 0. .00 XXXX6237

HETATM 6238 0 HOH s 392 39. .827 46. .283 54. .598 1. .00 0. .00 XXXX6238

HETATM 6239 0 HOH s 393 19. .234 66. .751 69. .837 1. .00 0. .00 XXXX6239

HETATM 6240 0 HOH s 394 -4. .291 46. .002 47. .331 1. .00 0. .00 XXXX6240

HETATM 6241 0 HOH s 395 -11. .891 28. .022 29. .272 1. .00 0. .00 XXXX6241

HETATM 6242 0 HOH s 396 14. .520 42. .767 32. .549 1. .00 0. .00 XXXX6242

HETATM 6243 0 HOH s 397 -32. .501 28. .433 54. .681 1. .00 0. .00 XXXX6243

HETATM 6244 0 HOH s 398 23. .957 27. .826 62. .993 1. .00 0. .00 XXXX6244

HETATM 6245 0 HOH s 399 -11. .326 49. .217 53. .239 1. .00 0. .00 XXXX6245

HETATM 6246 0 HOH s 400 -5. .967 34. .531 57. .340 1. .00 0. .00 XXXX6246

HETATM 6247 0 HOH s 401 16. .917 28. .735 65. .366 1. .00 0. .00 XXXX6247

HETATM 6248 0 HOH s 402 -7. .887 48. .303 52. .181 1. .00 0. .00 XXXX6248

HETATM 6249 0 HOH s 403 22. .220 53. .573 77. .611 1. .00 0. .00 XXXX6249

HETATM 6250 0 HOH s 404 4. .679 71. .760 49. .504 1. .00 0. .00 XXXX6250

HETATM 6251 0 HOH s 405 -41. .409 31. .428 35. .131 1. .00 0. .00 XXXX6251

HETATM 6252 0 HOH s 406 22. .888 24. .260 49. .853 1. .00 0. .00 XXXX6252

HETATM 6253 0 HOH s 407 -17. .344 27. .953 55. .427 1. .00 0. .00 XXXX6253

HETATM 6254 0 HOH s 408 -27. .958 33. .550 57. .565 1. .00 0. .00 XXXX6254

HETATM 6255 0 HOH s 409 3. .951 25. .397 51. .395 1. .00 0. .00 XXXX6255

HETATM 6256 0 HOH s 410 33. .657 52. .256 43. .298 1. .00 0. .00 XXXX6256

HETATM 6257 0 HOH s 411 -42. .052 40. .142 34. .104 1. .00 0. .00 XXXX6257

HETATM 6258 0 HOH s 412 -39. .716 46. .500 36. .315 1. .00 0. .00 XXXX6258

HETATM 6259 0 HOH s 413 6. .282 24. .794 46. .903 1. .00 0. .00 XXXX6259

HETATM 6260 0 HOH s 414 4. .245 43. .954 43. .687 1. .00 0. .00 XXXX6260

HETATM 6261 0 HOH s 415 18. .203 71. .493 60. .862 1. .00 0. .00 XXXX6261

HETATM 6262 0 HOH s 416 24. .278 21. .883 42. .563 1. .00 0. .00 XXXX6262

HETATM 6263 0 HOH s 417 26. .553 46. .195 32. .789 1. .00 0. .00 XXXX6263

HETATM 6264 0 HOH s 418 40. .498 33. .031 58. .215 1. .00 0. .00 XXXX6264

HETATM 6265 0 HOH s 419 -7. .612 58. .851 53. .870 1. .00 0. .00 XXXX6265

HETATM 6266 0 HOH s 420 -5. .108 66. .432 53. .148 1. .00 0. .00 XXXX6266

HETATM 6267 0 HOH s 421 12. .433 25. .133 43. .281 1. .00 0. .00 XXXX6267

HETATM 6268 0 HOH s 422 6. .281 60. .567 39. .414 1. .00 0. .00 XXXX6268

HETATM 6269 0 HOH s 423 -3. .346 31. .853 30. .331 1. .00 0. .00 XXXX6269

HETATM 6270 0 HOH s 424 -33. .061 26. .183 36. .379 1. .00 0. .00 XXXX6270

HETATM 6271 0 HOH s 425 -6. .877 28. .307 28. .596 1. .00 0. .00 XXXX6271

HETATM 6272 0 HOH s 426 6. .140 42. .489 42. .465 1. .00 0. .00 XXXX6272

HETATM 6273 0 HOH s 427 3. .477 68. .555 31. .558 1. .00 0. .00 XXXX6273

HETATM 6274 0 HOH s 428 -3. .532 68. .479 60. .026 1. .00 0. .00 XXXX6274

HETATM 6275 0 HOH s 429 12. .584 44. .823 73. .921 1. .00 0. .00 XXXX6275

HETATM 6276 0 HOH s 430 -15. .036 26. .121 47. .340 1. .00 0. .00 XXXX6276 Attorney Docket No. 35327-522001 WO

HETATM 6277 O HOH S 431 -1. .036 32. .294 61. .138 1. .00 0. .00 XXXX6277

HETATM 6278 O HOH s 432 -32. .481 51. .389 40. .859 1. .00 0. .00 XXXX6278

HETATM 6279 O HOH s 433 7. .856 35. .153 37. .348 1. .00 0. .00 XXXX6279

HETATM 6280 O HOH s 434 -8. .917 49. .606 53. .652 1. .00 0. .00 XXXX6280

HETATM 6281 O HOH s 435 6. .440 69. .929 64. .905 1. .00 0. .00 XXXX6281

HETATM 6282 O HOH s 436 -24. .797 61. .937 35. .334 1. .00 0. .00 XXXX6282

HETATM 6283 O HOH s 437 -12. .775 31. .809 23. .996 1. .00 0. .00 XXXX6283

HETATM 6284 O HOH s 438 -38. .516 47. .694 34. .475 1. .00 0. .00 XXXX6284

HETATM 6285 O HOH s 439 32. .325 51. .235 50. .196 1. .00 0. .00 XXXX6285

HETATM 6286 O HOH s 440 4. .808 46. .190 43. .479 1. .00 0. .00 XXXX6286

HETATM 6287 O HOH s 441 -15. .244 64. .045 18. .186 1. .00 0. .00 XXXX6287

HETATM 6288 O HOH s 442 20. .398 34. .676 31. .613 1. .00 0. .00 XXXX6288

HETATM 6289 O HOH s 443 8. .793 40. .673 29. .467 1. .00 0. .00 XXXX6289

HETATM 6290 O HOH s 444 -29. .527 55. .652 38. .746 1. .00 0. .00 XXXX6290

HETATM 6291 O HOH s 445 -24. .023 28. .373 27. .729 1. .00 0. .00 XXXX6291

HETATM 6292 O HOH s 446 42. .935 39. .988 58. .492 1. .00 0. .00 XXXX6292

HETATM 6293 O HOH s 447 -9. .266 72. .698 44. .657 1. .00 0. .00 XXXX6293

HETATM 6294 O HOH s 448 -21. .513 39. .561 60. .161 1. .00 0. .00 XXXX6294

HETATM 6295 O HOH s 449 -12. .922 68. .192 18. .762 1. .00 0. .00 XXXX6295

HETATM 6296 O HOH s 450 39. .468 42. .826 46. .760 1. .00 0. .00 XXXX6296

HETATM 6297 O HOH s 451 -12. .470 22. .430 46. .399 1. .00 0. .00 XXXX6297

HETATM 6298 O HOH s 452 41. .160 45. .055 62. .904 1. .00 0. .00 XXXX6298

HETATM 6299 O HOH s 453 17. .795 52. .319 76. .335 1. .00 0. .00 XXXX6299

HETATM 6300 O HOH s 454 5. .493 73. .426 50. .497 1. .00 0. .00 XXXX6300

HETATM 6301 O HOH s 455 -24. .373 27. .684 38. .287 1. .00 0. .00 XXXX6301

HETATM 6302 O HOH s 456 -17. .345 36. .981 59. .108 1. .00 0. .00 XXXX6302

HETATM 6303 O HOH s 457 16. .992 25. .106 61. .890 1. .00 0. .00 XXXX6303

HETATM 6304 0 HOH s 458 -19. .206 69. .119 32. .478 1. .00 0. .00 XXXX6304

HETATM 6305 0 HOH s 459 -25. .184 47. .093 59. .509 1. .00 0. .00 XXXX6305

HETATM 6306 0 HOH s 460 -31. .434 56. .150 26. .862 1. .00 0. .00 XXXX6306

HETATM 6307 0 HOH s 461 -13. .131 57. .112 69. .718 1. .00 0. .00 XXXX6307

HETATM 6308 0 HOH s 462 16. .785 68. .977 70. .514 1. .00 0. .00 XXXX6308

HETATM 6309 0 HOH s 463 39. .188 46. .172 60. .968 1. .00 0. .00 XXXX6309

HETATM 6310 0 HOH s 464 16. .879 21. .684 43. .758 1. .00 0. .00 XXXX6310

HETATM 6311 0 HOH s 465 -7. .146 66. .474 13. .771 1. .00 0. .00 XXXX6311

HETATM 6312 0 HOH s 466 7. .047 65. .757 77. .271 1. .00 0. .00 XXXX6312

HETATM 6313 0 HOH s 467 22. .485 33. .288 69. .996 1. .00 0. .00 XXXX6313

HETATM 6314 0 HOH s 468 -42. .948 40. .184 31. .889 1. .00 0. .00 XXXX6314

HETATM 6315 0 HOH s 469 16. .138 25. .020 51. .311 1. .00 0. .00 XXXX6315

HETATM 6316 0 HOH s 470 -10. .976 60. .411 52. .560 1. .00 0. .00 XXXX6316

HETATM 6317 0 HOH s 471 -18. .188 60. .790 22. .098 1. .00 0. .00 XXXX6317

HETATM 6318 0 HOH s 472 10. .456 26. .760 44. .189 1. .00 0. .00 XXXX6318

HETATM 6319 0 HOH s 473 -0. .346 66. .737 76. .934 1. .00 0. .00 XXXX6319

HETATM 6320 0 HOH s 474 -17. .800 27. .755 46. .757 1. .00 0. .00 XXXX6320

HETATM 6321 0 HOH s 475 -3. .665 30. .874 28. .475 1. .00 0. .00 XXXX6321

HETATM 6322 0 HOH s 476 -9. .220 34. .141 52. .047 1. .00 0. .00 XXXX6322

HETATM 6323 0 HOH s 477 24. .051 54. .557 72. .324 1. .00 0. .00 XXXX6323

HETATM 6324 0 HOH s 478 6. .466 52. .812 33. .935 1. .00 0. .00 XXXX6324

HETATM 6325 0 HOH s 479 7. .813 51. .866 60. .949 1. .00 0. .00 XXXX6325

HETATM 6326 0 HOH s 480 7. .474 23. .381 49. .022 1. .00 0. .00 XXXX6326

HETATM 6327 0 HOH s 481 2. .109 32. .523 32. .075 1. .00 0. .00 XXXX6327

HETATM 6328 0 HOH s 482 21. .146 59. .569 69. .600 1. .00 0. .00 XXXX6328

HETATM 6329 0 HOH s 483 -6. .117 71. .350 17. .974 1. .00 0. .00 XXXX6329

HETATM 6330 0 HOH s 484 -10. .570 22. .587 38. .502 1. .00 0. .00 XXXX6330

HETATM 6331 0 HOH s 485 -10. .624 57. .283 51. .874 1. .00 0. .00 XXXX6331

HETATM 6332 0 HOH s 486 27. .088 37. .475 66. .170 1. .00 0. .00 XXXX6332

HETATM 6333 0 HOH s 487 -27. .887 25. .867 40. .426 1. .00 0. .00 XXXX6333

HETATM 6334 0 HOH s 488 -11. .029 53. .729 54. .083 1. .00 0. .00 XXXX6334

HETATM 6335 0 HOH s 489 -22. .498 33. .312 20. .633 1. .00 0. .00 XXXX6335

HETATM 6336 0 HOH s 490 3. .185 67. .786 18. .519 1. .00 0. .00 XXXX6336

HETATM 6337 0 HOH s 491 42. .058 38. .319 63. .255 1. .00 0. .00 XXXX6337

HETATM 6338 0 HOH s 492 32. .229 55. .780 63. .927 1. .00 0. .00 XXXX6338

HETATM 6339 0 HOH s 493 -25. .506 31. .633 22. .120 1. .00 0. .00 XXXX6339

HETATM 6340 0 HOH s 494 14. .579 55. .129 40. .683 1. .00 0. .00 XXXX6340

HETATM 6341 0 HOH s 495 11. .433 35. .739 69. .226 1. .00 0. .00 XXXX6341

HETATM 6342 0 HOH s 496 -2. .652 36. .731 47. .392 1. .00 0. .00 XXXX6342

HETATM 6343 0 HOH s 497 -20. .753 64. .357 29. .227 1. .00 0. .00 XXXX6343 Attorney Docket No. 35327-522001 WO

HETATM 6344 O HOH S 498 10. .075 45. .933 28. .187 1. .00 0. .00 XXXX6344

HETATM 6345 O HOH s 499 -22. .394 50. .307 56. .261 1. .00 0. .00 XXXX6345

HETATM 6346 O HOH s 500 -33. .441 52. .433 23. .566 1. .00 0. .00 XXXX6346

HETATM 6347 O HOH s 501 12. .008 27. .594 60. .971 1. .00 0. .00 XXXX6347

HETATM 6348 O HOH s 502 -12. .737 25. .348 47. .255 1. .00 0. .00 XXXX6348

HETATM 6349 O HOH s 503 -36. .291 38. .225 22. .753 1. .00 0. .00 XXXX6349

HETATM 6350 O HOH s 504 -1. .503 53. .189 73. .358 1. .00 0. .00 XXXX6350

HETATM 6351 O HOH s 505 -11. .783 31. .796 26. .994 1. .00 0. .00 XXXX6351

HETATM 6352 O HOH s 506 1. .450 45. .636 76. .130 1. .00 0. .00 XXXX6352

HETATM 6353 O HOH s 507 -2. .806 69. .196 31. .083 1. .00 0. .00 XXXX6353

HETATM 6354 O HOH s 508 0. .717 68. .501 45. .555 1. .00 0. .00 XXXX6354

HETATM 6355 O HOH s 509 4. .379 32. .623 33. .023 1. .00 0. .00 XXXX6355

HETATM 6356 O HOH s 510 20. .773 48. .966 79. .260 1. .00 0. .00 XXXX6356

HETATM 6357 O HOH s 511 4. .954 60. .620 43. .034 1. .00 0. .00 XXXX6357

HETATM 6358 O HOH s 512 26. .385 33. .296 30. .932 1. .00 0. .00 XXXX6358

HETATM 6359 O HOH s 513 8. .730 28. .283 42. .348 1. .00 0. .00 XXXX6359

HETATM 6360 O HOH s 514 -40. .486 41. .980 36. .054 1. .00 0. .00 XXXX6360

HETATM 6361 O HOH s 515 7. .652 58. .689 37. .252 1. .00 0. .00 XXXX6361

HETATM 6362 O HOH s 516 -9. .499 30. .163 49. .151 1. .00 0. .00 XXXX6362

HETATM 6363 O HOH s 517 10. .101 22. .888 52. .994 1. .00 0. .00 XXXX6363

HETATM 6364 O HOH s 518 20. .630 64. .245 54. .262 1. .00 0. .00 XXXX6364

HETATM 6365 O HOH s 519 34. .892 50. .150 47. .211 1. .00 0. .00 XXXX6365

HETATM 6366 O HOH s 520 43. .485 45. .796 63. .300 1. .00 0. .00 XXXX6366

HETATM 6367 O HOH s 521 13. .675 37. .191 71. .129 1. .00 0. .00 XXXX6367

HETATM 6368 0 HOH s 522 11. .582 30. .157 61. .283 1. .00 0. .00 XXXX6368

HETATM 6369 0 HOH s 523 26. .778 35. .205 32. .107 1. .00 0. .00 XXXX6369

HETATM 6370 0 HOH s 524 -4. .823 32. .696 57. .107 1. .00 0. .00 XXXX6370

HETATM 6371 0 HOH s 525 21. .239 67. .611 57. .403 1. .00 0. .00 XXXX6371

HETATM 6372 0 HOH s 526 -4. .759 60. .928 48. .225 1. .00 0. .00 XXXX6372

HETATM 6373 0 HOH s 527 -22. .229 29. .799 60. .479 1. .00 0. .00 XXXX6373

HETATM 6374 0 HOH s 528 5. .425 68. .675 34. .631 1. .00 0. .00 XXXX6374

HETATM 6375 0 HOH s 529 -15. .601 23. .095 38. .940 1. .00 0. .00 XXXX6375

HETATM 6376 0 HOH s 530 9. .047 66. .572 43. .235 1. .00 0. .00 XXXX6376

HETATM 6377 0 HOH s 531 5. .601 64. .395 41. .505 1. .00 0. .00 XXXX6377

HETATM 6378 0 HOH s 532 -12. .951 37. .584 17. .013 1. .00 0. .00 XXXX6378

HETATM 6379 0 HOH s 533 -2. .663 68. .696 49. .350 1. .00 0. .00 XXXX6379

HETATM 6380 0 HOH s 534 33. .975 41. .068 70. .009 1. .00 0. .00 XXXX6380

HETATM 6381 0 HOH s 535 -6. .689 31. .211 48. .913 1. .00 0. .00 XXXX6381

HETATM 6382 0 HOH s 536 -26. .752 25. .017 50. .130 1. .00 0. .00 XXXX6382

HETATM 6383 0 HOH s 537 -10. .033 44. .518 56. .737 1. .00 0. .00 XXXX6383

HETATM 6384 0 HOH s 538 -3. .463 61. .798 11. .466 1. .00 0. .00 XXXX6384

HETATM 6385 0 HOH s 539 2. .686 66. .763 44. .853 1. .00 0. .00 XXXX6385

HETATM 6386 0 HOH s 540 -38. .889 46. .517 29. .892 1. .00 0. .00 XXXX6386

HETATM 6387 0 HOH s 541 -14. .864 46. .850 54. .084 1. .00 0. .00 XXXX6387

HETATM 6388 0 HOH s 542 36. .744 51. .002 53. .140 1. .00 0. .00 XXXX6388

HETATM 6389 0 HOH s 543 11. .802 47. .024 23. .130 1. .00 0. .00 XXXX6389

HETATM 6390 0 HOH s 544 -23. .606 51. .151 19. .173 1. .00 0. .00 XXXX6390

HETATM 6391 0 HOH s 545 3. .394 68. .044 41. .843 1. .00 0. .00 XXXX6391

HETATM 6392 0 HOH s 546 2. .340 33. .739 22. .333 1. .00 0. .00 XXXX6392

HETATM 6393 0 HOH s 547 5. .119 47. .572 41. .346 1. .00 0. .00 XXXX6393

HETATM 6394 0 HOH s 548 40. .799 41. .567 54. .882 1. .00 0. .00 XXXX6394

HETATM 6395 0 HOH s 549 -4. .644 71. .890 42. .159 1. .00 0. .00 XXXX6395

HETATM 6396 0 HOH s 550 -6. .487 37. .222 18. .613 1. .00 0. .00 XXXX6396

HETATM 6397 0 HOH s 551 -6. .470 70. .239 42. .745 1. .00 0. .00 XXXX6397

HETATM 6398 0 HOH s 552 -7. .932 51. .498 55. .177 1. .00 0. .00 XXXX6398

HETATM 6399 0 HOH s 553 -34. .698 50. .438 43. .930 1. .00 0. .00 XXXX6399

HETATM 6400 0 HOH s 554 -13. .581 37. .543 19. .644 1. .00 0. .00 XXXX6400

HETATM 6401 0 HOH s 555 -7. .667 52. .512 29. .947 1. .00 0. .00 XXXX6401

HETATM 6402 0 HOH s 556 12. .400 68. .640 72. .874 1. .00 0. .00 XXXX6402

HETATM 6403 0 HOH s 557 14. .987 25. .724 42. .736 1. .00 0. .00 XXXX6403

HETATM 6404 0 HOH s 558 -16. .154 59. .463 48. .714 1. .00 0. .00 XXXX6404

HETATM 6405 0 HOH s 559 12. .715 64. .116 74. .090 1. .00 0. .00 XXXX6405

HETATM 6406 0 HOH s 560 -35. .958 28. .308 45. .048 1. .00 0. .00 XXXX6406

HETATM 6407 0 HOH s 561 -10. .888 34. .519 56. .279 1. .00 0. .00 XXXX6407

HETATM 6408 0 HOH s 562 -21. .272 49. .158 11. .960 1. .00 0. .00 XXXX6408

HETATM 6409 0 HOH s 563 -7. .672 72. .208 24. .524 1. .00 0. .00 XXXX6409

HETATM 6410 0 HOH s 564 -28. .296 46. .350 18. .638 1. .00 0. .00 XXXX6410 Attorney Docket No. 35327-522001 WO

HETATM 6411 O HOH S 565 -21. .740 24. .054 44. .753 1. .00 0. .00 XXXX6411

HETATM 6412 O HOH s 566 -16. .237 66. .161 43. .448 1. .00 0. .00 XXXX6412

HETATM 6413 O HOH s 567 10. .928 59. .368 79. .601 1. .00 0. .00 XXXX6413

HETATM 6414 O HOH s 568 19. .489 45. .085 78. .478 1. .00 0. .00 XXXX6414

HETATM 6415 O HOH s 569 -17. .743 34. .507 58. .235 1. .00 0. .00 XXXX6415

HETATM 6416 O HOH s 570 -14. .162 26. .789 28. .480 1. .00 0. .00 XXXX6416

HETATM 6417 O HOH s 571 20. .769 67. .236 68. .110 1. .00 0. .00 XXXX6417

HETATM 6418 O HOH s 572 -25. .205 63. .659 33. .901 1. .00 0. .00 XXXX6418

HETATM 6419 O HOH s 573 -9. .314 46. .335 65. .282 1. .00 0. .00 XXXX6419

HETATM 6420 O HOH s 574 -11. .570 74. .367 28. .200 1. .00 0. .00 XXXX6420

HETATM 6421 O HOH s 575 10. .555 56. .773 39. .168 1. .00 0. .00 XXXX6421

HETATM 6422 O HOH s 576 -3. .872 49. .050 49. .868 1. .00 0. .00 XXXX6422

HETATM 6423 O HOH s 577 15. .489 54. .128 38. .915 1. .00 0. .00 XXXX6423

HETATM 6424 O HOH s 578 -3. .415 41. .515 47. .513 1. .00 0. .00 XXXX6424

HETATM 6425 O HOH s 579 16. .062 19. .827 63. .322 1. .00 0. .00 XXXX6425

HETATM 6426 O HOH s 580 -8. .683 53. .494 58. .438 1. .00 0. .00 XXXX6426

HETATM 6427 O HOH s 581 -6. .947 43. .804 15. .520 1. .00 0. .00 XXXX6427

HETATM 6428 O HOH s 582 16. .531 59. .696 42. .483 1. .00 0. .00 XXXX6428

HETATM 6429 O HOH s 583 -14. .254 27. .697 53. .827 1. .00 0. .00 XXXX6429

HETATM 6430 O HOH s 584 6. .711 65. .761 43. .827 1. .00 0. .00 XXXX6430

HETATM 6431 O HOH s 585 11. .342 25. .724 58. .481 1. .00 0. .00 XXXX6431

HETATM 6432 O HOH s 586 11. .018 67. .597 42. .699 1. .00 0. .00 XXXX6432

HETATM 6433 O HOH s 587 24. .333 27. .530 52. .676 1. .00 0. .00 XXXX6433

HETATM 6434 O HOH s 588 -31. .577 53. .934 26. .993 1. .00 0. .00 XXXX6434

HETATM 6435 O HOH s 589 -34. .759 50. .660 39. .667 1. .00 0. .00 XXXX6435

HETATM 6436 O HOH s 590 10. .948 35. .119 34. .464 1. .00 0. .00 XXXX6436

HETATM 6437 O HOH s 591 15. .554 62. .750 39. .153 1. .00 0. .00 XXXX6437

HETATM 6438 0 HOH s 592 8. .738 53. .695 32. .519 1. .00 0. .00 XXXX6438

HETATM 6439 0 HOH s 593 26. .416 28. .357 63. .417 1. .00 0. .00 XXXX6439

HETATM 6440 0 HOH s 594 8. .381 43. .024 28. .049 1. .00 0. .00 XXXX6440

HETATM 6441 0 HOH s 595 -2. .297 41. .214 44. .334 1. .00 0. .00 XXXX6441

HETATM 6442 0 HOH s 596 -8. .712 43. .529 62. .035 1. .00 0. .00 XXXX6442

HETATM 6443 0 HOH s 597 24. .684 48. .643 73. .090 1. .00 0. .00 XXXX6443

HETATM 6444 0 HOH s 598 25. .310 32. .130 68. .870 1. .00 0. .00 XXXX6444

HETATM 6445 0 HOH s 599 -1. .514 31. .101 69. .029 1. .00 0. .00 XXXX6445

HETATM 6446 0 HOH s 600 -19. .714 62. .336 22. .782 1. .00 0. .00 XXXX6446

HETATM 6447 0 HOH s 601 9. .448 67. .976 35. .382 1. .00 0. .00 XXXX6447

HETATM 6448 0 HOH s 602 -0. .645 68. .817 23. .665 1. .00 0. .00 XXXX6448

HETATM 6449 0 HOH s 603 18. .421 19. .792 43. .611 1. .00 0. .00 XXXX6449

HETATM 6450 0 HOH s 604 -14. .303 42. .157 58. .083 1. .00 0. .00 XXXX6450

HETATM 6451 0 HOH s 605 -25. .344 59. .111 43. .380 1. .00 0. .00 XXXX6451

HETATM 6452 0 HOH s 606 -3. .477 44. .179 44. .176 1. .00 0. .00 XXXX6452

HETATM 6453 0 HOH s 607 -4. .523 68. .035 29. .269 1. .00 0. .00 XXXX6453

HETATM 6454 0 HOH s 608 -8. .978 67. .758 15. .387 1. .00 0. .00 XXXX6454

HETATM 6455 0 HOH s 609 0. .887 32. .452 29. .378 1. .00 0. .00 XXXX6455

HETATM 6456 0 HOH s 610 2. .749 39. .313 45. .943 1. .00 0. .00 XXXX6456

HETATM 6457 0 HOH s 611 1. .353 31. .297 21. .100 1. .00 0. .00 XXXX6457

HETATM 6458 0 HOH s 612 -21. .473 46. .868 61. .541 1. .00 0. .00 XXXX6458

HETATM 6459 0 HOH s 613 13. .251 61. .166 79. .889 1. .00 0. .00 XXXX6459

HETATM 6460 0 HOH s 614 -8. .817 45. .358 15. .887 1. .00 0. .00 XXXX6460

HETATM 6461 0 HOH s 615 -7. .873 75. .792 41. .694 1. .00 0. .00 XXXX6461

HETATM 6462 0 HOH s 616 -0. .010 30. .612 57. .399 1. .00 0. .00 XXXX6462

HETATM 6463 0 HOH s 617 14. .778 32. .894 33. .689 1. .00 0. .00 XXXX6463

HETATM 6464 0 HOH s 618 -14. .824 68. .964 40. .252 1. .00 0. .00 XXXX6464

HETATM 6465 0 HOH s 619 19. .545 24. .815 46. .021 1. .00 0. .00 XXXX6465

HETATM 6466 0 HOH s 620 -22. .345 63. .435 34. .476 1. .00 0. .00 XXXX6466

HETATM 6467 0 HOH s 621 -9. .586 63. .883 8. .984 1. .00 0. .00 XXXX6467

HETATM 6468 0 HOH s 622 -10. .184 58. .117 58. .409 1. .00 0. .00 XXXX6468

HETATM 6469 0 HOH s 623 25. .893 25. .329 40. .761 1. .00 0. .00 XXXX6469

HETATM 6470 0 HOH s 624 18. .515 61. .892 42. .078 1. .00 0. .00 XXXX6470

HETATM 6471 0 HOH s 625 2. .685 41. .181 44. .207 1. .00 0. .00 XXXX6471

HETATM 6472 0 HOH s 626 -38. .534 58. .049 25. .801 1. .00 0. .00 XXXX6472

HETATM 6473 0 HOH s 627 -27. .253 49. .227 54. .712 1. .00 0. .00 XXXX6473

HETATM 6474 0 HOH s 628 -13. .191 72. .632 27. .140 1. .00 0. .00 XXXX6474

HETATM 6475 0 HOH s 629 16. .614 41. .086 31. .699 1. .00 0. .00 XXXX6475

HETATM 6476 0 HOH s 630 38. .760 43. .643 54. .402 1. .00 0. .00 XXXX6476

HETATM 6477 0 HOH s 631 -16. .895 61. .100 19. .929 1. .00 0. .00 XXXX6477 Attorney Docket No. 35327-522001 WO

HETATM 6478 O HOH S 632 8. .739 19. .963 44. .550 1. .00 0. .00 XXXX6478

HETATM 6479 O HOH s 633 16. .906 53. .700 78. .265 1. .00 0. .00 XXXX6479

HETATM 6480 O HOH s 634 7. .455 27. .702 57. .100 1. .00 0. .00 XXXX6480

HETATM 6481 O HOH s 635 4. .488 65. .991 15. .259 1. .00 0. .00 XXXX6481

HETATM 6482 O HOH s 636 -23. .997 61. .952 30. .808 1. .00 0. .00 XXXX6482

HETATM 6483 O HOH s 637 12. .616 73. .190 50. .358 1. .00 0. .00 XXXX6483

HETATM 6484 O HOH s 638 -18. .254 63. .331 50. .179 1. .00 0. .00 XXXX6484

HETATM 6485 O HOH s 639 3. .605 44. .071 46. .684 1. .00 0. .00 XXXX6485

HETATM 6486 O HOH s 640 -17. .585 60. .712 16. .203 1. .00 0. .00 XXXX6486

HETATM 6487 O HOH s 641 -10. .703 45. .034 14. .953 1. .00 0. .00 XXXX6487

HETATM 6488 O HOH s 642 -26. .581 56. .739 35. .171 1. .00 0. .00 XXXX6488

HETATM 6489 O HOH s 643 -14. .992 52. .536 52. .873 1. .00 0. .00 XXXX6489

HETATM 6490 O HOH s 644 -6. .199 42. .059 48. .225 1. .00 0. .00 XXXX6490

HETATM 6491 O HOH s 645 3. .440 61. .126 79. .559 1. .00 0. .00 XXXX6491

HETATM 6492 O HOH s 646 -14. .915 34. .609 19. .950 1. .00 0. .00 XXXX6492

HETATM 6493 O HOH s 647 32. .508 53. .060 48. .010 1. .00 0. .00 XXXX6493

HETATM 6494 O HOH s 648 25. .157 47. .661 31. .147 1. .00 0. .00 XXXX6494

HETATM 6495 O HOH s 649 -5. .411 52. .506 31. .480 1. .00 0. .00 XXXX6495

HETATM 6496 O HOH s 650 11. .157 71. .803 69. .407 1. .00 0. .00 XXXX6496

HETATM 6497 O HOH s 651 19. .480 65. .706 51. .187 1. .00 0. .00 XXXX6497

HETATM 6498 O HOH s 652 9. .607 58. .200 34. .943 1. .00 0. .00 XXXX6498

HETATM 6499 O HOH s 653 -22. .797 37. .286 60. .731 1. .00 0. .00 XXXX6499

HETATM 6500 O HOH s 654 -8. .832 27. .696 48. .215 1. .00 0. .00 XXXX6500

HETATM 6501 O HOH s 655 34. .018 42. .932 32. .302 1. .00 0. .00 XXXX6501

HETATM 6502 O HOH s 656 24. .327 60. .716 51. .312 1. .00 0. .00 XXXX6502

HETATM 6503 O HOH s 657 13. .024 71. .288 68. .348 1. .00 0. .00 XXXX6503

HETATM 6504 0 HOH s 658 -8. .490 37. .498 61. .852 1. .00 0. .00 XXXX6504

HETATM 6505 0 HOH s 659 -17. .917 60. .796 49. .547 1. .00 0. .00 XXXX6505

HETATM 6506 0 HOH s 660 16. .387 61. .601 70. .493 1. .00 0. .00 XXXX6506

HETATM 6507 0 HOH s 661 13. .583 38. .874 76. .335 1. .00 0. .00 XXXX6507

HETATM 6508 0 HOH s 662 10. .632 33. .131 35. .693 1. .00 0. .00 XXXX6508

HETATM 6509 0 HOH s 663 -28. .568 47. .301 16. .677 1. .00 0. .00 XXXX6509

HETATM 6510 0 HOH s 664 24. .539 35. .767 69. .936 1. .00 0. .00 XXXX6510

HETATM 6511 0 HOH s 665 27. .955 30. .070 65. .323 1. .00 0. .00 XXXX6511

HETATM 6512 0 HOH s 666 14. .341 26. .005 61. .997 1. .00 0. .00 XXXX6512

HETATM 6513 0 HOH s 667 28. .165 46. .588 72. .809 1. .00 0. .00 XXXX6513

HETATM 6514 0 HOH s 668 2. .648 71. .598 47. .450 1. .00 0. .00 XXXX6514

HETATM 6515 0 HOH s 669 -2. .048 33. .326 68. .232 1. .00 0. .00 XXXX6515

HETATM 6516 0 HOH s 670 27. .736 26. .238 51. .918 1. .00 0. .00 XXXX6516

HETATM 6517 0 HOH s 671 1. .983 32. .452 48. .886 1. .00 0. .00 XXXX6517

HETATM 6518 0 HOH s 672 24. .625 42. .548 71. .115 1. .00 0. .00 XXXX6518

HETATM 6519 0 HOH s 673 4. .943 67. .943 61. .873 1. .00 0. .00 XXXX6519

HETATM 6520 0 HOH s 674 -36. .723 50. .587 38. .047 1. .00 0. .00 XXXX6520

HETATM 6521 0 HOH s 675 0. .649 40. .873 45. .414 1. .00 0. .00 XXXX6521

HETATM 6522 0 HOH s 676 17. .112 51. .931 78. .733 1. .00 0. .00 XXXX6522

HETATM 6523 0 HOH s 677 -5. .002 30. .307 19. .077 1. .00 0. .00 XXXX6523

HETATM 6524 0 HOH s 678 -30. .729 50. .798 50. .598 1. .00 0. .00 XXXX6524

HETATM 6525 0 HOH s 679 -12. .583 48. .622 58. .948 1. .00 0. .00 XXXX6525

HETATM 6526 0 HOH s 680 14. .921 23. .371 61. .150 1. .00 0. .00 XXXX6526

HETATM 6527 0 HOH s 681 22. .883 63. .202 52. .948 1. .00 0. .00 XXXX6527

HETATM 6528 0 HOH s 682 -38. .982 27. .853 36. .895 1. .00 0. .00 XXXX6528

HETATM 6529 0 HOH s 683 24. .066 51. .826 77. .536 1. .00 0. .00 XXXX6529

HETATM 6530 0 HOH s 684 -8. .481 40. .459 61. .248 1. .00 0. .00 XXXX6530

HETATM 6531 0 HOH s 685 -11. .012 52. .613 58. .831 1. .00 0. .00 XXXX6531

HETATM 6532 0 HOH s 686 11. .471 54. .810 37. .062 1. .00 0. .00 XXXX6532

HETATM 6533 0 HOH s 687 -6. .270 70. .222 26. .573 1. .00 0. .00 XXXX6533

HETATM 6534 0 HOH s 688 6. .415 70. .022 60. .235 1. .00 0. .00 XXXX6534

HETATM 6535 0 HOH s 689 -3. .622 59. .382 10. .586 1. .00 0. .00 XXXX6535

HETATM 6536 0 HOH s 690 12. .040 47. .457 31. .596 1. .00 0. .00 XXXX6536

HETATM 6537 0 HOH s 691 -38. .319 28. .337 41. .109 1. .00 0. .00 XXXX6537

HETATM 6538 0 HOH s 692 4. .558 67. .442 26. .648 1. .00 0. .00 XXXX6538

HETATM 6539 0 HOH s 693 -22. .058 27. .800 24. .949 1. .00 0. .00 XXXX6539

HETATM 6540 0 HOH s 694 -7. .227 23. .212 41. .360 1. .00 0. .00 XXXX6540

HETATM 6541 0 HOH s 695 3. .137 69. .800 17. .456 1. .00 0. .00 XXXX6541

HETATM 6542 0 HOH s 696 -25. .732 59. .347 21. .930 1. .00 0. .00 XXXX6542

HETATM 6543 0 HOH s 697 -36. .115 45. .989 47. .890 1. .00 0. .00 XXXX6543

HETATM 6544 0 HOH s 698 -15. .361 62. .404 52. .130 1. .00 0. .00 XXXX6544 Attorney Docket No. 35327-522001 WO

HETATM 6545 O HOH S 699 5. .565 27. .133 46. .315 1. .00 0. .00 XXXX6545

HETATM 6546 O HOH s 700 -10. .187 45. .988 62. .513 1. .00 0. .00 XXXX6546

HETATM 6547 O HOH s 701 37. .028 51. .077 61. .782 1. .00 0. .00 XXXX6547

HETATM 6548 O HOH s 702 21. .280 29. .311 30. .776 1. .00 0. .00 XXXX6548

HETATM 6549 O HOH s 703 -21. .806 37. .691 17. .673 1. .00 0. .00 XXXX6549

HETATM 6550 O HOH s 704 38. .559 50. .484 59. .776 1. .00 0. .00 XXXX6550

HETATM 6551 O HOH s 705 28. .707 26. .766 39. .742 1. .00 0. .00 XXXX6551

HETATM 6552 O HOH s 706 -6. .648 38. .178 64. .711 1. .00 0. .00 XXXX6552

HETATM 6553 O HOH s 707 26. .332 61. .258 57. .229 1. .00 0. .00 XXXX6553

HETATM 6554 O HOH s 708 -5. .879 31. .360 46. .876 1. .00 0. .00 XXXX6554

HETATM 6555 O HOH s 709 -19. .857 64. .886 37. .210 1. .00 0. .00 XXXX6555

HETATM 6556 O HOH s 710 -40. .217 28. .554 34. .544 1. .00 0. .00 XXXX6556

HETATM 6557 O HOH s 711 4. .664 69. .577 38. .800 1. .00 0. .00 XXXX6557

HETATM 6558 O HOH s 712 22. .313 20. .954 49. .405 1. .00 0. .00 XXXX6558

HETATM 6559 O HOH s 713 21. .463 37. .018 72. .833 1. .00 0. .00 XXXX6559

HETATM 6560 O HOH s 714 12. .743 37. .879 73. .657 1. .00 0. .00 XXXX6560

HETATM 6561 O HOH s 715 9. .637 35. .081 70. .991 1. .00 0. .00 XXXX6561

HETATM 6562 O HOH s 716 33. .904 58. .502 64. .528 1. .00 0. .00 XXXX6562

HETATM 6563 O HOH s 717 2. .474 66. .451 27. .146 1. .00 0. .00 XXXX6563

HETATM 6564 O HOH s 718 -4. .775 63. .209 49. .237 1. .00 0. .00 XXXX6564

HETATM 6565 O HOH s 719 31. .760 52. .818 64. .061 1. .00 0. .00 XXXX6565

HETATM 6566 O HOH s 720 -21. .085 67. .820 29. .354 1. .00 0. .00 XXXX6566

HETATM 6567 O HOH s 721 -22. .587 63. .309 32. .528 1. .00 0. .00 XXXX6567

HETATM 6568 0 HOH s 722 -25. .865 61. .002 24. .161 1. .00 0. .00 XXXX6568

HETATM 6569 0 HOH s 723 -0. .806 69. .159 64. .304 1. .00 0. .00 XXXX6569

HETATM 6570 0 HOH s 724 29. .454 28. .174 37. .273 1. .00 0. .00 XXXX6570

HETATM 6571 0 HOH s 725 5. .985 72. .681 58. .809 1. .00 0. .00 XXXX6571

HETATM 6572 0 HOH s 726 -2. .218 66. .617 63. .830 1. .00 0. .00 XXXX6572

HETATM 6573 0 HOH s 727 -22. .071 49. .195 59. .119 1. .00 0. .00 XXXX6573

HETATM 6574 0 HOH s 728 -2. .414 72. .585 16. .770 1. .00 0. .00 XXXX6574

HETATM 6575 0 HOH s 729 14. .550 50. .107 36. .158 1. .00 0. .00 XXXX6575

HETATM 6576 0 HOH s 730 11. .838 69. .413 49. .589 1. .00 0. .00 XXXX6576

HETATM 6577 0 HOH s 731 -13. .044 30. .877 19. .324 1. .00 0. .00 XXXX6577

HETATM 6578 0 HOH s 732 -14. .909 33. .857 17. .589 1. .00 0. .00 XXXX6578

HETATM 6579 0 HOH s 733 12. .908 55. .927 35. .408 1. .00 0. .00 XXXX6579

HETATM 6580 0 HOH s 734 -10. .066 36. .878 16. .454 1. .00 0. .00 XXXX6580

HETATM 6581 0 HOH s 735 9. .016 41. .149 26. .700 1. .00 0. .00 XXXX6581

HETATM 6582 0 HOH s 736 -39. .348 51. .114 18. .333 1. .00 0. .00 XXXX6582

HETATM 6583 0 HOH s 737 -17. .203 28. .960 25. .219 1. .00 0. .00 XXXX6583

HETATM 6584 0 HOH s 738 19. .982 61. .319 49. .197 1. .00 0. .00 XXXX6584

HETATM 6585 0 HOH s 739 -20. .325 30. .158 23. .241 1. .00 0. .00 XXXX6585

HETATM 6586 0 HOH s 740 -5. .940 54. .861 11. .869 1. .00 0. .00 XXXX6586

HETATM 6587 0 HOH s 741 4. .979 75. .183 56. .623 1. .00 0. .00 XXXX6587

HETATM 6588 0 HOH s 742 -1. .528 41. .768 64. .931 1. .00 0. .00 XXXX6588

HETATM 6589 0 HOH s 743 -27. .293 51. .766 51. .774 1. .00 0. .00 XXXX6589

HETATM 6590 0 HOH s 744 -14. .481 44. .561 15. .399 1. .00 0. .00 XXXX6590

HETATM 6591 0 HOH s 745 28. .127 33. .618 33. .171 1. .00 0. .00 XXXX6591

HETATM 6592 0 HOH s 746 19. .167 20. .086 46. .695 1. .00 0. .00 XXXX6592

HETATM 6593 0 HOH s 747 1. .772 42. .015 25. .903 1. .00 0. .00 XXXX6593

HETATM 6594 0 HOH s 748 8. .954 45. .820 30. .597 1. .00 0. .00 XXXX6594

HETATM 6595 0 HOH s 749 -5. .387 47. .402 49. .608 1. .00 0. .00 XXXX6595

HETATM 6596 0 HOH s 750 7. .856 52. .117 36. .032 1. .00 0. .00 XXXX6596

HETATM 6597 0 HOH s 751 -5. .519 41. .976 16. .113 1. .00 0. .00 XXXX6597

HETATM 6598 0 HOH s 752 -35. .826 44. .709 52. .938 1. .00 0. .00 XXXX6598

HETATM 6599 0 HOH s 753 12. .547 21. .090 41. .921 1. .00 0. .00 XXXX6599

HETATM 6600 0 HOH s 754 38. .911 44. .743 51. .145 1. .00 0. .00 XXXX6600

HETATM 6601 0 HOH s 755 10. .564 67. .673 28. .165 1. .00 0. .00 XXXX6601

HETATM 6602 0 HOH s 756 2. .624 74. .574 57. .833 1. .00 0. .00 XXXX6602

HETATM 6603 0 HOH s 757 32. .290 28. .920 45. .727 1. .00 0. .00 XXXX6603

HETATM 6604 0 HOH s 758 -7. .105 53. .078 32. .682 1. .00 0. .00 XXXX6604

HETATM 6605 0 HOH s 759 19. .269 51. .169 78. .558 1. .00 0. .00 XXXX6605

HETATM 6606 0 HOH s 760 -27. .824 49. .407 17. .099 1. .00 0. .00 XXXX6606

HETATM 6607 0 HOH s 761 7. .100 46. .499 31. .497 1. .00 0. .00 XXXX6607

HETATM 6608 0 HOH s 762 17. .898 70. .441 57. .963 1. .00 0. .00 XXXX6608

HETATM 6609 0 HOH s 763 -13. .968 50. .747 54. .305 1. .00 0. .00 XXXX6609

HETATM 6610 0 HOH s 764 9. .746 26. .963 60. .651 1. .00 0. .00 XXXX6610

HETATM 6611 0 HOH s 765 -33. .341 55. .725 27. .503 1. .00 0. .00 XXXX6611 Attorney Docket No. 35327-522001 WO

HETATM 6612 O HOH S 766 10. .335 76. .971 51. .340 1. .00 0. .00 XXXX6612

HETATM 6613 O HOH s 767 -4. .505 27. .949 27. .150 1. .00 0. .00 XXXX6613

HETATM 6614 O HOH s 768 -0. .216 74. .213 16. .627 1. .00 0. .00 XXXX6614

HETATM 6615 O HOH s 769 -6. .401 40. .349 17. .056 1. .00 0. .00 XXXX6615

HETATM 6616 O HOH s 770 -6. .126 48. .023 67. .363 1. .00 0. .00 XXXX6616

HETATM 6617 O HOH s 771 -38. .535 29. .040 55. .425 1. .00 0. .00 XXXX6617

HETATM 6618 O HOH s 772 20. .525 57. .506 43. .457 1. .00 0. .00 XXXX6618

HETATM 6619 O HOH s 773 11. .325 41. .053 26. .006 1. .00 0. .00 XXXX6619

HETATM 6620 O HOH s 774 -10. .111 74. .427 37. .857 1. .00 0. .00 XXXX6620

HETATM 6621 O HOH s 775 -31. .861 29. .041 45. .881 1. .00 0. .00 XXXX6621

HETATM 6622 O HOH s 776 33. .679 51. .909 67. .937 1. .00 0. .00 XXXX6622

HETATM 6623 O HOH s 777 23. .598 57. .435 72. .986 1. .00 0. .00 XXXX6623

HETATM 6624 O HOH s 778 -30. .401 26. .146 41. .623 1. .00 0. .00 XXXX6624

HETATM 6625 O HOH s 779 -17. .634 64. .319 44. .278 1. .00 0. .00 XXXX6625

HETATM 6626 O HOH s 780 -9. .143 35. .713 19. .227 1. .00 0. .00 XXXX6626

HETATM 6627 O HOH s 781 -35. .501 28. .064 42. .905 1. .00 0. .00 XXXX6627

HETATM 6628 O HOH s 782 -3. .573 28. .828 40. .210 1. .00 0. .00 XXXX6628

HETATM 6629 O HOH s 783 -0. .574 68. .728 75. .124 1. .00 0. .00 XXXX6629

HETATM 6630 O HOH s 784 -13. .447 38. .447 14. .717 1. .00 0. .00 XXXX6630

HETATM 6631 O HOH s 785 1. .730 43. .426 45. .712 1. .00 0. .00 XXXX6631

HETATM 6632 O HOH s 786 -4. .308 25. .122 39. .219 1. .00 0. .00 XXXX6632

HETATM 6633 O HOH s 787 -14. .976 70. .487 38. .583 1. .00 0. .00 XXXX6633

HETATM 6634 O HOH s 788 -22. .975 54. .219 13. .549 1. .00 0. .00 XXXX6634

HETATM 6635 O HOH s 789 16. .156 67. .008 46. .982 1. .00 0. .00 XXXX6635

HETATM 6636 O HOH s 790 2. .164 45. .511 43. .355 1. .00 0. .00 XXXX6636

HETATM 6637 O HOH s 791 -16. .308 41. .119 58. .933 1. .00 0. .00 XXXX6637

HETATM 6638 O HOH s 792 10. .419 65. .451 33. .731 1. .00 0. .00 XXXX6638

HETATM 6639 0 HOH s 793 24. .969 49. .879 75. .788 1. .00 0. .00 XXXX6639

HETATM 6640 0 HOH s 794 39. .469 43. .399 49. .030 1. .00 0. .00 XXXX6640

HETATM 6641 0 HOH s 795 -24. .132 27. .795 59. .065 1. .00 0. .00 XXXX6641

HETATM 6642 0 HOH s 796 10. .585 66. .256 30. .838 1. .00 0. .00 XXXX6642

HETATM 6643 0 HOH s 797 6. .923 37. .692 72. .710 1. .00 0. .00 XXXX6643

HETATM 6644 0 HOH s 798 23. .397 33. .970 28. .832 1. .00 0. .00 XXXX6644

HETATM 6645 0 HOH s 799 15. .631 22. .185 41. .290 1. .00 0. .00 XXXX6645

HETATM 6646 0 HOH s 800 5. .363 65. .746 22. .559 1. .00 0. .00 XXXX6646

HETATM 6647 0 HOH s 801 10. .829 46. .043 34. .923 1. .00 0. .00 XXXX6647

HETATM 6648 0 HOH s 802 -6. .078 60. .707 51. .322 1. .00 0. .00 XXXX6648

HETATM 6649 0 HOH s 803 16. .614 67. .920 44. .228 1. .00 0. .00 XXXX6649

HETATM 6650 0 HOH s 804 -25. .810 60. .388 36. .781 1. .00 0. .00 XXXX6650

HETATM 6651 0 HOH s 805 -1. .701 70. .140 48. .105 1. .00 0. .00 XXXX6651

HETATM 6652 0 HOH s 806 -1. .134 75. .556 53. .152 1. .00 0. .00 XXXX6652

HETATM 6653 0 HOH s 807 24. .188 45. .902 73. .602 1. .00 0. .00 XXXX6653

HETATM 6654 0 HOH s 808 -30. .132 27. .973 25. .335 1. .00 0. .00 XXXX6654

HETATM 6655 0 HOH s 809 19. .043 65. .533 41. .093 1. .00 0. .00 XXXX6655

HETATM 6656 0 HOH s 810 13. .097 41. .489 76. .504 1. .00 0. .00 XXXX6656

HETATM 6657 0 HOH s 811 7. .767 76. .289 52. .275 1. .00 0. .00 XXXX6657

HETATM 6658 0 HOH s 812 -7. .386 26. .367 50. .016 1. .00 0. .00 XXXX6658

HETATM 6659 0 HOH s 813 -10. .961 65. .366 52. .185 1. .00 0. .00 XXXX6659

HETATM 6660 0 HOH s 814 -7. .274 27. .914 33. .425 1. .00 0. .00 XXXX6660

HETATM 6661 0 HOH s 815 17. .131 48. .782 33. .387 1. .00 0. .00 XXXX6661

HETATM 6662 0 HOH s 816 5. .845 70. .445 73. .607 1. .00 0. .00 XXXX6662

HETATM 6663 0 HOH s 817 22. .154 61. .981 70. .044 1. .00 0. .00 XXXX6663

HETATM 6664 0 HOH s 818 -0. .817 29. .748 22. .132 1. .00 0. .00 XXXX6664

HETATM 6665 0 HOH s 819 -2. .377 73. .909 54. .257 1. .00 0. .00 XXXX6665

HETATM 6666 0 HOH s 820 -13. .975 57. .751 51. .413 1. .00 0. .00 XXXX6666

HETATM 6667 0 HOH s 821 17. .891 67. .085 42. .361 1. .00 0. .00 XXXX6667

HETATM 6668 0 HOH s 822 13. .302 47. .106 34. .954 1. .00 0. .00 XXXX6668

HETATM 6669 0 HOH s 823 29. .463 27. .781 65. .145 1. .00 0. .00 XXXX6669

HETATM 6670 0 HOH s 824 -23. .897 60. .488 40. .038 1. .00 0. .00 XXXX6670

HETATM 6671 0 HOH s 825 -33. .635 28. .181 44. .735 1. .00 0. .00 XXXX6671

HETATM 6672 0 HOH s 826 8. .365 32. .492 71. .456 1. .00 0. .00 XXXX6672

HETATM 6673 0 HOH s 827 22. .236 27. .280 65. .405 1. .00 0. .00 XXXX6673

HETATM 6674 0 HOH s 828 21. .195 66. .157 55. .327 1. .00 0. .00 XXXX6674

HETATM 6675 0 HOH s 829 26. .794 59. .304 49. .705 1. .00 0. .00 XXXX6675

HETATM 6676 0 HOH s 830 37. .031 51. .621 57. .177 1. .00 0. .00 XXXX6676

HETATM 6677 0 HOH s 831 37. .803 54. .193 56. .138 1. .00 0. .00 XXXX6677

HETATM 6678 0 HOH s 832 3. .557 76. .334 47. .673 1. .00 0. .00 XXXX6678 Attorney Docket No. 35327-522001 WO

HETATM 6679 O HOH S 833 -27. .270 56. .609 46. .541 1. .00 0. .00 XXXX6679

HETATM 6680 O HOH s 834 -40. .136 56. .196 26. .580 1. .00 0. .00 XXXX6680

HETATM 6681 O HOH s 835 -23. .935 61. .760 24. .721 1. .00 0. .00 XXXX6681

HETATM 6682 O HOH s 836 -8. .403 46. .003 9. .825 1. .00 0. .00 XXXX6682

HETATM 6683 O HOH s 837 -4. .193 65. .973 76. .624 1. .00 0. .00 XXXX6683

HETATM 6684 O HOH s 838 -20. .341 27. .916 58. .768 1. .00 0. .00 XXXX6684

HETATM 6685 O HOH s 839 -36. .616 52. .070 34. .629 1. .00 0. .00 XXXX6685

HETATM 6686 O HOH s 840 -35. .854 26. .640 38. .868 1. .00 0. .00 XXXX6686

HETATM 6687 O HOH s 841 0. .477 67. .267 14. .347 1. .00 0. .00 XXXX6687

HETATM 6688 O HOH s 842 -29. .466 45. .855 52. .906 1. .00 0. .00 XXXX6688

HETATM 6689 O HOH s 843 -23. .533 38. .456 18. .984 1. .00 0. .00 XXXX6689

HETATM 6690 O HOH s 844 -39. .064 48. .377 40. .823 1. .00 0. .00 XXXX6690

HETATM 6691 O HOH s 845 -24. .919 37. .212 21. .047 1. .00 0. .00 XXXX6691

HETATM 6692 O HOH s 846 -37. .377 44. .458 48. .447 1. .00 0. .00 XXXX6692

HETATM 6693 O HOH s 847 -1. .291 66. .136 46. .268 1. .00 0. .00 XXXX6693

HETATM 6694 O HOH s 848 10. .719 18. .407 42. .906 1. .00 0. .00 XXXX6694

HETATM 6695 O HOH s 849 9. .875 18. .160 45. .008 1. .00 0. .00 XXXX6695

HETATM 6696 O HOH s 850 14. .325 69. .036 67. .922 1. .00 0. .00 XXXX6696

HETATM 6697 O HOH s 851 21. .780 24. .432 45. .230 1. .00 0. .00 XXXX6697

HETATM 6698 O HOH s 852 24. .481 62. .718 70. .733 1. .00 0. .00 XXXX6698

HETATM 6699 O HOH s 853 2. .511 61. .835 13. .698 1. .00 0. .00 XXXX6699

HETATM 6700 O HOH s 854 11. .276 19. .485 45. .547 1. .00 0. .00 XXXX6700

HETATM 6701 O HOH s 855 14. .941 52. .513 37. .842 1. .00 0. .00 XXXX6701

HETATM 6702 O HOH s 856 -28. .952 47. .891 53. .264 1. .00 0. .00 XXXX6702

HETATM 6703 O HOH s 857 -37. .802 49. .883 41. .183 1. .00 0. .00 XXXX6703

HETATM 6704 O HOH s 858 31. .839 27. .999 65. .008 1. .00 0. .00 XXXX6704

HETATM 6705 0 HOH s 859 32. .537 30. .222 44. .037 1. .00 0. .00 XXXX6705

HETATM 6706 0 HOH s 860 27. .736 56. .836 54. .826 1. .00 0. .00 XXXX6706

HETATM 6707 0 HOH s 861 -31. .372 26. .820 36. .721 1. .00 0. .00 XXXX6707

HETATM 6708 0 HOH s 862 20. .583 64. .365 70. .499 1. .00 0. .00 XXXX6708

HETATM 6709 0 HOH s 863 -6. .187 63. .770 51. .047 1. .00 0. .00 XXXX6709

HETATM 6710 0 HOH s 864 14. .063 27. .675 36. .573 1. .00 0. .00 XXXX6710

HETATM 6711 0 HOH s 865 1. .504 44. .769 47. .220 1. .00 0. .00 XXXX6711

HETATM 6712 0 HOH s 866 33. .962 60. .259 66. .696 1. .00 0. .00 XXXX6712

HETATM 6713 0 HOH s 867 28. .598 47. .263 34. .145 1. .00 0. .00 XXXX6713

HETATM 6714 0 HOH s 868 -29. .551 57. .177 34. .357 1. .00 0. .00 XXXX6714

HETATM 6715 0 HOH s 869 -19. .167 61. .255 46. .315 1. .00 0. .00 XXXX6715

HETATM 6716 0 HOH s 870 -6. .386 25. .058 43. .539 1. .00 0. .00 XXXX6716

HETATM 6717 0 HOH s 871 -10. .360 50. .700 11. .946 1. .00 0. .00 XXXX6717

HETATM 6718 0 HOH s 872 -3. .933 67. .533 45. .799 1. .00 0. .00 XXXX6718

HETATM 6719 0 HOH s 873 33. .390 47. .485 37. .497 1. .00 0. .00 XXXX6719

HETATM 6720 0 HOH s 874 26. .578 42. .688 32. .283 1. .00 0. .00 XXXX6720

HETATM 6721 0 HOH s 875 -26. .419 61. .610 28. .906 1. .00 0. .00 XXXX6721

HETATM 6722 0 HOH s 876 -42. .642 42. .743 34. .833 1. .00 0. .00 XXXX6722

HETATM 6723 0 HOH s 877 -4. .920 64. .636 75. .304 1. .00 0. .00 XXXX6723

HETATM 6724 0 HOH s 878 7. .885 66. .715 31. .259 1. .00 0. .00 XXXX6724

HETATM 6725 0 HOH s 879 -27. .222 28. .290 27. .390 1. .00 0. .00 XXXX6725

HETATM 6726 0 HOH s 880 -15. .175 56. .349 68. .631 1. .00 0. .00 XXXX6726

HETATM 6727 0 HOH s 881 -31. .610 26. .388 45. .609 1. .00 0. .00 XXXX6727

HETATM 6728 0 HOH s 882 19. .762 69. .242 52. .533 1. .00 0. .00 XXXX6728

HETATM 6729 0 HOH s 883 -13. .131 63. .650 68. .734 1. .00 0. .00 XXXX6729

HETATM 6730 0 HOH s 884 28. .257 26. .740 62. .595 1. .00 0. .00 XXXX6730

HETATM 6731 0 HOH s 885 33. .441 49. .644 42. .016 1. .00 0. .00 XXXX6731

HETATM 6732 0 HOH s 886 17. .899 26. .481 65. .487 1. .00 0. .00 XXXX6732

HETATM 6733 0 HOH s 887 1. .875 69. .824 22. .081 1. .00 0. .00 XXXX6733

HETATM 6734 0 HOH s 888 -13. .248 53. .548 61. .667 1. .00 0. .00 XXXX6734

HETATM 6735 0 HOH s 889 17. .957 29. .370 68. .066 1. .00 0. .00 XXXX6735

HETATM 6736 0 HOH s 890 -18. .979 63. .344 45. .891 1. .00 0. .00 XXXX6736

HETATM 6737 0 HOH s 891 20. .725 67. .520 53. .781 1. .00 0. .00 XXXX6737

HETATM 6738 0 HOH s 892 -22. .605 25. .999 57. .298 1. .00 0. .00 XXXX6738

HETATM 6739 0 HOH s 893 -36. .626 50. .950 42. .996 1. .00 0. .00 XXXX6739

HETATM 6740 0 HOH s 894 -29. .638 55. .344 50. .345 1. .00 0. .00 XXXX6740

HETATM 6741 0 HOH s 895 30. .129 50. .586 39. .132 1. .00 0. .00 XXXX6741

HETATM 6742 0 HOH s 896 -31. .330 55. .813 35. .254 1. .00 0. .00 XXXX6742

HETATM 6743 0 HOH s 897 13. .507 62. .834 37. .640 1. .00 0. .00 XXXX6743

HETATM 6744 0 HOH s 898 -28. .307 29. .299 25. .946 1. .00 0. .00 XXXX6744

HETATM 6745 0 HOH s 899 10. .293 43. .017 37. .880 1. .00 0. .00 XXXX6745 Attorney Docket No. 35327-522001 WO

HETATM 6746 O HOH S 900 4. .490 39. .008 43. .859 1. .00 0. .00 XXXX6746

HETATM 6747 O HOH s 901 20. .201 29. .887 67. .386 1. .00 0. .00 XXXX6747

HETATM 6748 O HOH s 902 -0. .828 64. .410 79. .218 1. .00 0. .00 XXXX6748

HETATM 6749 O HOH s 903 19. .254 27. .900 44. .059 1. .00 0. .00 XXXX6749

HETATM 6750 O HOH s 904 11. .741 49. .010 37. .539 1. .00 0. .00 XXXX6750

HETATM 6751 O HOH s 905 4. .033 63. .279 11. .977 1. .00 0. .00 XXXX6751

HETATM 6752 O HOH s 906 28. .328 60. .144 51. .530 1. .00 0. .00 XXXX6752

HETATM 6753 O HOH s 907 0. .614 62. .975 79. .686 1. .00 0. .00 XXXX6753

HETATM 6754 O HOH s 908 31. .078 29. .716 40. .300 1. .00 0. .00 XXXX6754

HETATM 6755 O HOH s 909 21. .386 35. .514 29. .086 1. .00 0. .00 XXXX6755

HETATM 6756 O HOH s 910 27. .565 33. .818 65. .358 1. .00 0. .00 XXXX6756

HETATM 6757 O HOH s 911 -9. .301 29. .451 20. .142 1. .00 0. .00 XXXX6757

HETATM 6758 O HOH s 912 5. .919 37. .428 70. .756 1. .00 0. .00 XXXX6758

HETATM 6759 O HOH s 913 -13. .611 46. .456 64. .400 1. .00 0. .00 XXXX6759

HETATM 6760 O HOH s 914 21. .288 25. .617 62. .274 1. .00 0. .00 XXXX6760

HETATM 6761 O HOH s 915 5. .201 29. .643 47. .094 1. .00 0. .00 XXXX6761

HETATM 6762 O HOH s 916 -14. .565 48. .843 55. .393 1. .00 0. .00 XXXX6762

HETATM 6763 O HOH s 917 -23. .340 34. .202 61. .787 1. .00 0. .00 XXXX6763

HETATM 6764 O HOH s 918 -31. .196 56. .444 20. .319 1. .00 0. .00 XXXX6764

HETATM 6765 O HOH s 919 -6. .028 24. .562 50. .755 1. .00 0. .00 XXXX6765

HETATM 6766 O HOH s 920 -33. .295 49. .228 48. .787 1. .00 0. .00 XXXX6766

HETATM 6767 O HOH s 921 -12. .864 68. .038 45. .376 1. .00 0. .00 XXXX6767

HETATM 6768 O HOH s 922 20. .163 24. .249 61. .253 1. .00 0. .00 XXXX6768

HETATM 6769 O HOH s 923 21. .512 65. .453 64. .084 1. .00 0. .00 XXXX6769

HETATM 6770 0 HOH s 924 -24. .100 64. .908 26. .944 1. .00 0. .00 XXXX6770

HETATM 6771 0 HOH s 925 32. .638 29. .452 41. .941 1. .00 0. .00 XXXX6771

HETATM 6772 0 HOH s 926 -8. .768 65. .109 53. .969 1. .00 0. .00 XXXX6772

HETATM 6773 0 HOH s 927 -11. .845 56. .296 59. .354 1. .00 0. .00 XXXX6773

HETATM 6774 0 HOH s 928 -29. .444 57. .764 22. .344 1. .00 0. .00 XXXX6774

HETATM 6775 0 HOH s 929 3. .252 27. .036 67. .955 1. .00 0. .00 XXXX6775

HETATM 6776 0 HOH s 930 -13. .118 45. .189 62. .531 1. .00 0. .00 XXXX6776

HETATM 6777 0 HOH s 931 -3. .960 66. .888 72. .056 1. .00 0. .00 XXXX6777

HETATM 6778 0 HOH s 932 -7. .090 70. .010 16. .108 1. .00 0. .00 XXXX6778

HETATM 6779 0 HOH s 933 9. .752 72. .831 47. .677 1. .00 0. .00 XXXX6779

HETATM 6780 0 HOH s 934 23. .012 30. .523 69. .927 1. .00 0. .00 XXXX6780

HETATM 6781 0 HOH s 935 -9. .722 29. .588 22. .728 1. .00 0. .00 XXXX6781

HETATM 6782 0 HOH s 936 -12. .262 33. .545 18. .741 1. .00 0. .00 XXXX6782

HETATM 6783 0 HOH s 937 21. .596 66. .205 61. .776 1. .00 0. .00 XXXX6783

HETATM 6784 0 HOH s 938 -20. .640 25. .466 28. .217 1. .00 0. .00 XXXX6784

HETATM 6785 0 HOH s 939 -42. .734 55. .487 26. .210 1. .00 0. .00 XXXX6785

HETATM 6786 0 HOH s 940 23. .520 26. .375 59. .599 1. .00 0. .00 XXXX6786

HETATM 6787 0 HOH s 941 26. .978 43. .200 35. .666 1. .00 0. .00 XXXX6787

HETATM 6788 0 HOH s 942 -14. .717 43. .692 53. .650 1. .00 0. .00 XXXX6788

HETATM 6789 0 HOH s 943 -3. .090 68. .407 27. .290 1. .00 0. .00 XXXX6789

HETATM 6790 0 HOH s 944 5. .583 44. .175 24. .838 1. .00 0. .00 XXXX6790

HETATM 6791 0 HOH s 945 24. .577 41. .168 67. .535 1. .00 0. .00 XXXX6791

HETATM 6792 0 HOH s 946 -11. .491 68. .412 65. .369 1. .00 0. .00 XXXX6792

HETATM 6793 0 HOH s 947 -14. .022 41. .780 55. .558 1. .00 0. .00 XXXX6793

HETATM 6794 0 HOH s 948 -1. .563 68. .725 13. .890 1. .00 0. .00 XXXX6794

HETATM 6795 0 HOH s 949 29. .379 46. .776 38. .197 1. .00 0. .00 XXXX6795

HETATM 6796 0 HOH s 950 -20. .146 56. .293 47. .854 1. .00 0. .00 XXXX6796

HETATM 6797 0 HOH s 951 13. .395 67. .707 46. .029 1. .00 0. .00 XXXX6797

HETATM 6798 0 HOH s 952 13. .837 57. .844 39. .369 1. .00 0. .00 XXXX6798

HETATM 6799 0 HOH s 953 -2. .425 66. .932 25. .988 1. .00 0. .00 XXXX6799

HETATM 6800 0 HOH s 954 -14. .119 22. .583 34. .581 1. .00 0. .00 XXXX6800

HETATM 6801 0 HOH s 955 25. .764 25. .505 58. .850 1. .00 0. .00 XXXX6801

HETATM 6802 0 HOH s 956 26. .043 26. .523 50. .465 1. .00 0. .00 XXXX6802

HETATM 6803 0 HOH s 957 -15. .316 36. .349 19. .271 1. .00 0. .00 XXXX6803

HETATM 6804 0 HOH s 958 38. .842 51. .736 49. .240 1. .00 0. .00 XXXX6804

HETATM 6805 0 HOH s 959 -18. .829 40. .265 10. .903 1. .00 0. .00 XXXX6805

HETATM 6806 0 HOH s 960 20. .193 53. .354 78. .650 1. .00 0. .00 XXXX6806

HETATM 6807 0 HOH s 961 -35. .856 29. .703 30. .038 1. .00 0. .00 XXXX6807

HETATM 6808 0 HOH s 962 -5. .977 45. .169 12. .980 1. .00 0. .00 XXXX6808

HETATM 6809 0 HOH s 963 -1. .814 30. .536 53. .580 1. .00 0. .00 XXXX6809

HETATM 6810 0 HOH s 964 19. .790 17. .897 48. .238 1. .00 0. .00 XXXX6810

HETATM 6811 0 HOH s 965 34. .144 55. .354 48. .367 1. .00 0. .00 XXXX6811

HETATM 6812 0 HOH s 966 12. .495 64. .259 20. .978 1. .00 0. .00 XXXX6812 Attorney Docket No. 35327-522001 WO

HETATM 6813 O HOH S 967 32. .189 54. .666 51. .696 1. .00 0. .00 XXXX6813

HETATM 6814 O HOH s 968 21. .345 68. .534 70. .885 1. .00 0. .00 XXXX6814

HETATM 6815 O HOH s 969 5. .465 66. .546 24. .582 1. .00 0. .00 XXXX6815

HETATM 6816 O HOH s 970 -13. .028 65. .416 58. .829 1. .00 0. .00 XXXX6816

HETATM 6817 O HOH s 971 18. .469 34. .890 32. .195 1. .00 0. .00 XXXX6817

HETATM 6818 O HOH s 972 -4. .767 69. .356 55. .849 1. .00 0. .00 XXXX6818

HETATM 6819 O HOH s 973 0. .560 69. .696 15. .646 1. .00 0. .00 XXXX6819

HETATM 6820 O HOH s 974 0. .281 30. .357 52. .499 1. .00 0. .00 XXXX6820

HETATM 6821 O HOH s 975 11. .404 65. .072 38. .409 1. .00 0. .00 XXXX6821

HETATM 6822 O HOH s 976 29. .895 55. .136 51. .484 1. .00 0. .00 XXXX6822

HETATM 6823 O HOH s 977 -28. .777 46. .509 56. .933 1. .00 0. .00 XXXX6823

HETATM 6824 O HOH s 978 -7. .676 24. .679 36. .551 1. .00 0. .00 XXXX6824

HETATM 6825 O HOH s 979 -8. .051 40. .707 50. .082 1. .00 0. .00 XXXX6825

HETATM 6826 O HOH s 980 -17. .967 55. .388 49. .956 1. .00 0. .00 XXXX6826

HETATM 6827 O HOH s 981 34. .870 51. .037 70. .223 1. .00 0. .00 XXXX6827

HETATM 6828 O HOH s 982 32. .506 55. .158 49. .601 1. .00 0. .00 XXXX6828

HETATM 6829 O HOH s 983 23. .700 62. .354 56. .270 1. .00 0. .00 XXXX6829

HETATM 6830 O HOH s 984 19. .627 51. .697 35. .799 1. .00 0. .00 XXXX6830

HETATM 6831 O HOH s 985 -22. .795 59. .790 12. .087 1. .00 0. .00 XXXX6831

HETATM 6832 O HOH s 986 5. .552 30. .742 30. .976 1. .00 0. .00 XXXX6832

HETATM 6833 O HOH s 987 -10. .607 65. .401 57. .239 1. .00 0. .00 XXXX6833

HETATM 6834 O HOH s 988 -30. .903 57. .981 24. .450 1. .00 0. .00 XXXX6834

HETATM 6835 O HOH s 989 -16. .064 22. .776 36. .045 1. .00 0. .00 XXXX6835

HETATM 6836 O HOH s 990 28. .353 45. .765 36. .282 1. .00 0. .00 XXXX6836

HETATM 6837 O HOH s 991 -34. .166 55. .196 43. .455 1. .00 0. .00 XXXX6837

HETATM 6838 O HOH s 992 -11. .827 57. .308 72. .407 1. .00 0. .00 XXXX6838

HETATM 6839 O HOH s 993 -21. .653 38. .763 62. .737 1. .00 0. .00 XXXX6839

HETATM 6840 0 HOH s 994 -0. .296 64. .008 45. .692 1. .00 0. .00 XXXX6840

HETATM 6841 0 HOH s 995 38. .569 43. .668 42. .152 1. .00 0. .00 XXXX6841

HETATM 6842 0 HOH s 996 -10. .046 68. .104 62. .957 1. .00 0. .00 XXXX6842

HETATM 6843 0 HOH s 997 19. .056 49. .212 32. .709 1. .00 0. .00 XXXX6843

HETATM 6844 0 HOH s 998 -27. .009 33. .650 25. .830 1. .00 0. .00 XXXX6844

HETATM 6845 0 HOH s 999 7. .807 43. .869 25. .780 1. .00 0. .00 XXXX6845

HETATM 6846 0 HOH S1000 -8. .901 64. .020 50. .307 1. .00 0. .00 XXXX6846

HETATM 6847 0 HOH S1001 -32. .720 51. .820 49. .096 1. .00 0. .00 XXXX6847

HETATM 6848 0 HOH S1002 24. .558 52. .096 75. .118 1. .00 0. .00 XXXX6848

HETATM 6849 0 HOH S1003 19. .044 23. .304 47. .687 1. .00 0. .00 XXXX6849

HETATM 6850 0 HOH S1004 -20. .867 42. .883 16. .441 1. .00 0. .00 XXXX6850

HETATM 6851 0 HOH S1005 -17. .606 47. .900 59. .117 1. .00 0. .00 XXXX6851

HETATM 6852 0 HOH S1006 21. .125 58. .402 40. .637 1. .00 0. .00 XXXX6852

HETATM 6853 0 HOH S1007 11. .253 62. .165 37. .657 1. .00 0. .00 XXXX6853

HETATM 6854 0 HOH S1008 29. .319 48. .408 37. .239 1. .00 0. .00 XXXX6854

HETATM 6855 0 HOH S1009 -29. .395 61. .128 25. .439 1. .00 0. .00 XXXX6855

HETATM 6856 0 HOH S1010 36. .767 50. .827 47. .958 1. .00 0. .00 XXXX6856

HETATM 6857 0 HOH S1011 -28. .071 59. .425 31. .480 1. .00 0. .00 XXXX6857

HETATM 6858 0 HOH S1012 10. .026 33. .895 68. .317 1. .00 0. .00 XXXX6858

HETATM 6859 0 HOH S1013 -10. .535 38. .988 13. .104 1. .00 0. .00 XXXX6859

HETATM 6860 0 HOH S1014 -44. .354 57. .320 25. .738 1. .00 0. .00 XXXX6860

HETATM 6861 0 HOH S1015 37. .906 29. .684 47. .815 1. .00 0. .00 XXXX6861

HETATM 6862 0 HOH S1016 10. .397 36. .496 74. .537 1. .00 0. .00 XXXX6862

HETATM 6863 0 HOH S1017 0. .206 76. .782 55. .121 1. .00 0. .00 XXXX6863

HETATM 6864 0 HOH S1018 -36. .492 46. .976 50. .938 1. .00 0. .00 XXXX6864

HETATM 6865 0 HOH S1019 11. .021 24. .925 40. .808 1. .00 0. .00 XXXX6865

HETATM 6866 0 HOH S1020 31. .661 26. .756 54. .291 1. .00 0. .00 XXXX6866

HETATM 6867 0 HOH S1021 -23. .520 55. .061 51. .378 1. .00 0. .00 XXXX6867

HETATM 6868 0 HOH S1022 -12. .628 40. .385 14. .213 1. .00 0. .00 XXXX6868

HETATM 6869 0 HOH S1023 -32. .009 56. .271 45. .501 1. .00 0. .00 XXXX6869

HETATM 6870 0 HOH S1024 22. .542 26. .340 55. .016 1. .00 0. .00 XXXX6870

HETATM 6871 0 HOH S1025 -2. .770 31. .387 32. .890 1. .00 0. .00 XXXX6871

HETATM 6872 0 HOH S1026 -26. .522 28. .773 35. .903 1. .00 0. .00 XXXX6872

HETATM 6873 0 HOH S1027 -42. .767 50. .323 29. .541 1. .00 0. .00 XXXX6873

HETATM 6874 0 HOH S1028 -41. .201 53. .032 29. .570 1. .00 0. .00 XXXX6874

HETATM 6875 0 HOH S1029 17. .767 63. .319 46. .777 1. .00 0. .00 XXXX6875

HETATM 6876 0 HOH S1030 7. .050 43. .249 75. .581 1. .00 0. .00 XXXX6876

HETATM 6877 0 HOH S1031 38. .724 28. .635 44. .734 1. .00 0. .00 XXXX6877

HETATM 6878 0 HOH S1032 -13. .191 71. .446 36. .920 1. .00 0. .00 XXXX6878

HETATM 6879 0 HOH S1033 16. .376 65. .640 27. .715 1. .00 0. .00 XXXX6879 Attorney Docket No. 35327-522001 WO

HETATM 6880 O HOH S1034 14. .787 47. .607 36. .755 1. .00 0. .00 XXXX6880

HETATM 6881 O HOH S1035 8. .194 44. .673 74. .584 1. .00 0. .00 XXXX6881

HETATM 6882 O HOH S1036 -9. .186 55. .111 56. .517 1. .00 0. .00 XXXX6882

HETATM 6883 O HOH S1037 19. .260 63. .223 45. .010 1. .00 0. .00 XXXX6883

HETATM 6884 O HOH S1038 -13. .786 29. .019 55. .336 1. .00 0. .00 XXXX6884

HETATM 6885 O HOH S1039 40. .228 29. .212 46. .245 1. .00 0. .00 XXXX6885

HETATM 6886 O HOH S1040 21. .339 26. .952 52. .392 1. .00 0. .00 XXXX6886

HETATM 6887 O HOH S1041 -1. .982 71. .555 18. .696 1. .00 0. .00 XXXX6887

HETATM 6888 O HOH S1042 10. .061 44. .977 75. .397 1. .00 0. .00 XXXX6888

HETATM 6889 O HOH S1043 15. .915 65. .590 30. .418 1. .00 0. .00 XXXX6889

HETATM 6890 O HOH S1044 -3. .479 67. .467 12. .554 1. .00 0. .00 XXXX6890

HETATM 6891 O HOH S1045 25. .005 61. .744 37. .778 1. .00 0. .00 XXXX6891

HETATM 6892 O HOH S1046 -24. .467 47. .130 16. .957 1. .00 0. .00 XXXX6892

HETATM 6893 O HOH S1047 -37. .949 53. .961 34. .527 1. .00 0. .00 XXXX6893

HETATM 6894 O HOH S1048 25. .573 57. .854 74. .013 1. .00 0. .00 XXXX6894

HETATM 6895 O HOH S1049 -26. .778 28. .090 33. .740 1. .00 0. .00 XXXX6895

HETATM 6896 O HOH S1050 -30. .520 63. .362 24. .121 1. .00 0. .00 XXXX6896

HETATM 6897 O HOH S1051 -3. .837 28. .586 42. .983 1. .00 0. .00 XXXX6897

HETATM 6898 O HOH S1052 -20. .810 63. .133 36. .562 1. .00 0. .00 XXXX6898

HETATM 6899 O HOH S1053 23. .608 57. .083 43. .544 1. .00 0. .00 XXXX6899

HETATM 6900 O HOH S1054 18. .649 63. .905 70. .596 1. .00 0. .00 XXXX6900

HETATM 6901 O HOH S1055 23. .543 59. .967 39. .164 1. .00 0. .00 XXXX6901

HETATM 6902 O HOH S1056 23. .806 68. .226 70. .171 1. .00 0. .00 XXXX6902

HETATM 6903 O HOH S1057 -33. .439 25. .330 44. .410 1. .00 0. .00 XXXX6903

HETATM 6904 O HOH S1058 31. .907 53. .824 67. .417 1. .00 0. .00 XXXX6904

HETATM 6905 0 HOH S1059 -14. .310 43. .817 59. .455 1. .00 0. .00 XXXX6905

HETATM 6906 0 HOH S1060 4. .421 66. .579 29. .538 1. .00 0. .00 XXXX6906

HETATM 6907 0 HOH S1061 8. .180 37. .916 28. .975 1. .00 0. .00 XXXX6907

HETATM 6908 0 HOH S1062 -26. .740 60. .599 33. .581 1. .00 0. .00 XXXX6908

HETATM 6909 0 HOH S1063 6. .876 26. .895 58. .844 1. .00 0. .00 XXXX6909

EXAMPLE 10. MATERIALS AND METHODS

Bioinformatic searches. Annotated genomic and plasmid sequences of 5062 prokaryotes were obtained from the National Center of Biotechnology Information

(ftp://ftp.ncbi.nih.gov/genomes/Bacteria/all.gbk.tar.gz;) , together with annotations recording prokaryotic lifestyles (../ProkaryotesOrganismlnfo.txt). The Protein Databank (PDB) was obtained from www.rcsb.org. The obtained genomic and structural data files were organized into pre-processed two databases (PG, prokaryotic genomes; PDB). The 'ProteinHunter' program provides an interface and methods for organizing, querying, and analyzing these databases. ProteinHunter comprises a graphical user interface, set of computer scripts, and a parallel computing environment. Together these set up the calculations, manage the flow of information and execution in each of the calculation phases, control other programs that carry out specific calculations such as BLAST (Altschul et al., 1990, JMol Biol, 215, 403-10) and ClustalW (Chenna et al., 2003, Nucleic Acids Res, 31, 3497-500), and visualize the results. Genomic contextual analysis was carried using the OntologyMgr' and 'LinkageViewer' programs. The former creates a database that integrates multiple homology searches produced by ProteinHunter using different seed sequences, and the latter examines neighborhood relationships between members of two or more homolog sets. Attorney Docket No. 35327-522001 WO

OntologyMgr loads in the lists of homolog sequences identified in ProteinHunter searches, recording their identifier (<Genome accession>|<Protein ID>), and location in the host genome sequence (stored as the start and stop coordinates DNA coordinates within the full genomic sequence of the open reading frame, and the strand on which the open reading frame is located: 'forward' or 'reverse'), and stores them in easily retrievable format.

Linkage Viewer reads in this information and assembles lists of open reading frames that are located in the same operon within a genome. For instance, let the ProteinHunter has identified three independent homolog sets, each seeded with a periplasmic binding protein, an ABC transporter ATPase, and an ABC transporter permease sequence, respectively.

Linkage Viewer then produces lists of operons that contain the binding protein, the ATPase and the permease. To generate such predicted operons, LinkageViewer first assembles lists of all three components within a given genome (i.e. sub-lists of all components that share the same genome accession code). Next it identifies combinations members drawn from each list, which are located within the same operon. Operons are defined as follows: all members are located on the same strand (forward or reversed); members are connected within a string of open reading frames whose successive stop-start codons are no more than a maximum distance apart (inter-cistronic distance limit; set to 100 bases in the calculations reported here). There may be other genes in such predicted operons; the three requested components need not be immediate neighbors; nor is their order within an operon specified. Both programs are implemented as Python scripts.

To construct homolog sequence sets, single sequence seeds were extracted from either preprocessed PDB or PG databases. Homolog sets were then identified in the PDB or PG by using a seed sequence for a uni-directional BLAST search. A pairwise BLAST alignment was scored in ProteinHunter as a homolog hit if it exceeded a minimum fraction of identical residues and if the alignment covered at least 70% of the probe and target sequences.

To infer function using genomic context analysis, homolog sets were loaded into the OntologyMgr database, which was then queried by LinkageViewer. The latter assembles lists of possible operons in a genome by identifying polycistron strings of open reading frames (ORFs) that are located on the same strand (i.e. point in the same direction) and are separated by no more than a maximum intergenic distance (typically 100 bases). Homolog sets are then combined to identify members drawn from each sets, that are co-localized in the same polycistron. A member of the paAmiC homolog set was inferred to be a urea-binding Attorney Docket No. 35327-522001 WO protein if it is located in the same polycistron as a urease homolog or a combination of ABC transporter components, as described in the main text.

Function also can be inferred using the sequence of primary complementary surface (PCS) residues. A 7-residue, non-contiguous sequence comprising the PCS between the protein and the bound acetamide in the lpea structure (FIG. 3 and Table 1) was identified using ProteinHunter. PCS residues were selected as members of the PCS if the calculated distance between any of their atoms and any acetamide atom was less than 5A, and the distances between their backbone C _a and any atom in acetamide was greater than that of their Cp atom and any atom in acetamide. Secondary shell residues that do not form hydrogen bonds or van der Waals contacts were removed by inspection from the resulting set. To determine the PCS sequence of members in the paAmiC homolog set identified in

ProteinHunter, their sequences were aligned using ClustalW (Chenna et al., 2003, Nucleic Acids Res, 31, 3497-500). This alignment identifies the positions of the PCS residues in each homolog, from which the corresponding PCS sequence in that homology is then read. By combining this structure-based sequence information with the functional assignment using genomic context described above, the likely identity of residues in the PCS of urea-binding proteins was deduced (Table 1).

The putative urea-binding PCS filter was used to identify the subset of UBPs in the paAmiC homolog set. For each homolog, the number of PCS mutations relative to the urea- binding PCS (Hamming distance, Hpcs) was counted. Homologs with Hpcs=0 were inferred to be urea-binding proteins. The PCS sequences were displayed sorted by their H _P cs values, and within each Hpcs value sorted by their fraction identical residues, indicating the replicon within which they reside (chromosome or plasmid), whether this replicon contains paralogs, and the temperature tolerance (hyperthermophile, thermophile, mesophile, psychrophile, unknown), their Gram stain classification (if known), and the percentage genomic AT content. Duplicate hits were removed automatically from this list if the organism name (genus and species), fractional identity and paralogs were the same. From this list representative, unique UBP homologs with H _P cs=0 were chosen by inspection. In a subsequent phase of the analysis, the three-dimensional structure of csUBP7 was used to construct a known urea-binding PCS filter, and a new UBP homolog subset calculated (Table 1)·

Gene synthesis and mutagenesis. The amino acid sequences for the predicted UBP homologs identified in the bioinformatic search (see above) were extracted from the PG Attorney Docket No. 35327-522001 WO database. The putative leader peptide that mediates anchoring of the periplasmic-binding protein on the outside of the membrane (Gram positive bacteria) or directs secretion into the periplasm (Gram negative bacteria) was deleted by examining the multiple sequence alignment and removing the sequences N-teiminal to the start of the mature UBP amino acid sequence. The likely start of mature protein sequences was well-defined in this alignment, but a number of different start points were explored in design of the protein expression constructs (FIG. 6). Endogenous cysteines were changed to alanine. A hexahistidine tag was placed behind a GGS linker at the C-terminus of the mature protein to enable metal- mediated affinity purification (Hengen, 1995, Adv Healthc Mater, 2, 43-56). For three variants, the hyperacidic region used in the FATT tag (Sangawa et al., 2013, Protein Sci, 22, 840-50) followed by a rhinovirus C3 protease cleavage site (Cordingley et al. 1990 J. Biol. Chem., 265, 9062-9065) was fused to their amino termini. The final amino acid sequences were back-translated into a DNA sequence encoding the open reading frame (ORF), which was placed in a construct behind an efficient Shine-Dalgarno ribosome-binding site, and flanked by a T7 promoter and terminator at the 5' and 3' ends respectively, using the GeneFab program (Cox et al., 2007, Protein Sci, 16, 379-90). The resulting ORF sequences were optimized in context by OrfOpt program designed to predict highly expressed mRNA sequences in E. coli (see below). The resulting DNA sequences were synthesized by oligonucleotide assembly and cloned into pUC57 by GeneWiz, Inc. (South Plainfield, New Jersey).

Subsequent single and multiple point mutations were designed by preparing mutant sequences of the synthetic ORF sequences using the GfMutagenesis program that introduces point mutations into an ORF using the most prevalent codon in E. coli for an amino acid. Constructs for site-specific double labeling were designed by inserting the βΖίί domain sequence (Smith et al., 2005, Protein Sci, 14, 64-73) before the hexa-histidine C-terminal purification tag. All variants also were constructed by total gene synthesis.

Synthetic gene optimization. The OrfOpt program (U.S. Patent Publication No. 2011/0171737, incorporated by reference) uses stochastic optimization algorithms that alter choose different codons within an ORF without altering the amino acid sequence to optimize a target function designed to identify mRNA sequences that express proteins at high levels in E. coli. The OrfOpt simultaneously imposes AU-rich nucleotide composition at the 5' and 3' ends of the ORF, low RNA secondary structure content and favorable codon usage (Allert et al., 2010, JMol Biol, 402, 905-18). Attorney Docket No. 35327-522001 WO

Protein expression, purification, and fluorescent conjugate preparation. Plasmids carrying the expression constructs (see above) were transformed into KRX competent cells (Promega), and grown overnight at 37 °C on LB agar plates (100 mg/mL ampicillin). A single colony was picked and grown overnight at 37 °C in Terrific Broth (TB; Research Products International). The overnight cultures were diluted 1:20 in 500 mL TB (100 mg/mL ampicillin), grown to an optical density of ₆ οο ⁼ 0.5 at 37 °C in vigorously aerated shaker flasks, induced by the addition of 2.5 mL rhamnose (20 % w/v), and grown for a further 3-4 hrs. The cells were harvested by centrifugation (5,000 rpm, 10 min). After decanting the supernatant, the cell pellets were stored -80 °C. The cell pellets were thawed, resuspended in 8 mL binding buffer (10 mM imadozole, 20 mM MOPS, 500 mM NaCl, pH 7.8). Following resuspension, 3 mL of BugBuster HT (EMD Millipore) was added. After incubation (20 mins, 25 °C), the cells were lysed on ice by sonication (2 minutes of one-second on/off pulses, 20-30% power). A clarified lysate was prepared by centrifugation (15,000 rpm, 20 min, 4 °C) from which recombinant protein was purified by batch immobilized metal affinity chromatography (IMAC). Resuspended IMAC agarose beads (5 mL; Sigma-Aldrich, P6611) were added to the lysate. After incubation at 4 °C in a Mini LabRoller (Labnet International) for 1 hr, the beads were washed at least five times with binding buffer. The immobilized protein beads were resuspended in labeling buffer (20 mM MOPS, 100 mM NaCl, pH 6.9) and labeled overnight (4 °C, rotating end-over-end) with a thiol-reactive fluorophore (5-fold stoichiometric excess over protein). Following two rinses with labeling buffer to remove unincorporated label, the proteins were eluted from the beads. For double labeling of βΖίί fusions, a second thiol-reactive label was added following reduction of the disulfide with 5 mM TCEP. To elute labeled protein from the IMAC beads, 6 mL of elution buffer (400 mM imidazole, 500 mM NaCl, 20 mM MOPS, pH 7.8) was added, incubated for 30 min (4 °C, rotating end-over-end), and the beads removed by centrifugation. Following dialysis of the eluate against three changes of assay buffer (20 mM MOPS, 20 mM KC1, pH 7.4), using 10 kDa semi-perimeable membrane (Snakeskin tubing, Thermo Scientific), the fluorescent conjugates were concentrated in a 10 kDa cutoff spin concentrator (Vivaspin, GE

Healthcare). Protein purity was assessed by SDS/PAGE. Protein concentrations were determined by (NanodroplOOO) at 280 nm (using extinction coefficients calculated from their sequence (Gill and von Hippel, 1989, Anal Biochem, 182, 319-26; Artimo et al., 2012, Nucleic Acids Res, 40, W597-603), or at the fluorophore absorbance peak (Acrylodan, 391 nm and Badan, 387 nm). Attorney Docket No. 35327-522001 WO

Determination of temperature- and ligand-dependent fluorescence landscapes. 12-, 24-, or 48-point logarithmic titration series were prepared on a Tecan Freedom liquid- handling robot, using an in-house program, 'TitrationPlate', that compiles an abstract description of a multi-component titration series into machine instructions for operating the robot. Urea concentrations were varied from 0-4.8 M in 20 mM KC1, 20 mM MOPS (pH 7.4). Temperature-dependent fluorescence emission intensities of 20 μΐ _^ aliquots, each containing 10 μΜ protein, were measured in 384-well microtiter plates in a LightCycler 480 II (Roche) using excitation and emission wavelengths available for this instrument that most closely matched the optical characteristics of the fluorescent conjugate. Temperatures were advanced in IK steps. At each temperature, data was collected at 1 -second intervals for 60 seconds at which point the signal had relaxed to a steady value associated with the new temperature. Under these experimental photobleaching was not observed. The in-house program 'TitrationMeltPlate' was used to convert these observations into time-independent datasets that record fluorescence as a function of temperature for each well and associate wells with their concentration of titrant and additive. Management tools were developed to maintain a database of titrations and their analyses.

Determination of emission intensity spectra. Ligand- and wavelength-dependent emission intensities were recorded on a Nanodrop3300 (Thermo Scientific) at room temperature. Using the LED closest to the optimal excitation wavelength of the fiuorophore (UV, 365 nm; blue, 470 nm; 'white', 460-550 nm).

Ratiometric analysis of urea binding. Isothermal urea titrations were extracted from the fluorescent landscape or emission spectra datasets obtained as described above.

Monochromatic emission intensities 1 _% (these intensities correspond to a bandpass intensity, recorded either with a physical filter in the case of the Roche LightCycler, or by integrating in the interval λ-δ, λ+δ in the case of an emission spectrum), were fit to where ^αρ °β _λ and ° ^α 'β _λ are the fluorescence baselines associated with the ligand-free and ligand-bound states of the protein, respectively, and y^ the fractional saturation of the protein (Layton and Hellinga, 2010, Biochemistry, 49, 10831-41). Baseline functions can be constant, linear, or a second-order polynomial. For the ligand- and temperature-dependent fluorescence landscapes, we use a constant value for ^αρο β _χ , but ^sat _x is described by a linear dependence on urea concentration, [L]: Attorney Docket No. 35327-522001 WO

single urea-binding site, the fractional saturation is given by

where [L] is the ligand (urea) concentration and.¾ the dissociation constant, for y^.

A ratiometric signal at a given point in a titration series, i? ₁₂ (t), is given by the ratio of intensiti in the emission spectrum measured at that point: where a _t is an attenuation factor that describes the effect of variations in sample size {i.e. the amount of observable fluorophore) in the ί ^Λ sample on the wavelength-independent intensity of the entire emission spectrum. This signal removes wavelength-independent emission intensity attenuation effects due to variations in conjugate concentration, photobleaching, fluctuations in excitation source intensities, and detection efficiency (Demchenko, 2010, J Fluoresc, 20, 1099-128; Demchenko, 2014, Journal of Molecular Structure, 1077, 51-67). It is a key aspect for high-precision sensing using the reagentless fluorescently-responsive sensors described here. The ratiometric signal also can be fit to a binding isotherm: where ^αρο β _κ and ^sat /3 _R are the baselines, and y _R the apparent fractional saturation of the protein (with " ). In general, ^t ""K _d ≠ ^pp K _d ; if both baselines are constant, a simple relationship can be derived relating ^app K _& to (Grimley et al., 2013, JNeurosci, 33, 16297-309):

where ^αρο Ι ι and ^sat I\2 are the emission intensities of the monochromatic signal at wavelength λ ₂ of the ligand-free and ligand-bound protein, respectively.

Following a fit of the titration series using equations 4 and 5, a _t values can be recovered by taking the average comparison of the observed and calculated intensities at the two wavelengths: Attorney Docket No. 35327-522001 WO

The a _t value can then be applied to all wavelengths to obtain an emission spectrum or integrated intensity of the ί ^Λ titration point corrected for variations in sample size:

a" ^T l{X) = a _t ^obs l{X) 8 where ^corr I( ) and ^ohs I(X) are the wavelength-dependent intensities of the corrected and observed emission spectra, respectively.

The fractional error in the chemometric concentration measurement, depends on the first derivative of the binding isotherm as follows (Marvin et al., 1997, Proc Natl Acad Sci U

-71):

where i? _1;2 is the ratiometric signal (equation 5), £· _1;2 its experimental error, and SS is the resulting chemometric error in the concentration. We can then define a relative precision function

where P(S) is the relative precision at concentration S, which reaches a maximum value (i.e. lowest error), max, at the K^.

For a given isothermal titration, values for ^app K& and were obtained using a nonlinear fitting algorithm in which these two parameters were simultaneously fit to the three experimental binding isotherms using equations 1 and 5, with the two monochromatic isotherms sharing the same value. Three separate pairs of ^αρ °β and " ^α> β were fit in this procedure, corresponding to the two monochromatic and the ratiometric signals, respectively. Two distinct ratiometric response models can be used: coupled (both wavelengths respond to ligand); uncoupled ( the second wavelength is non-responsive; i.e. remains constant).

Optionally, an attenuation vector, a(t) containg a _t values for each titration point (equation 7), can be refined by iterative fit cycles in which the a(t) vector of a previous cycle is used to adjust the integrated intensities of the next cycle. Programs 'Nanodrop3300' and

'TitrationMeltAnalysis' were developed to analyze wavelength- or temperature-dependent ligand-binding datasets respectively. Attorney Docket No. 35327-522001 WO

Analysis of urea-binding properties using thermal melts. The thermal stability of purified UBP candidate proteins was determined by measuring the temperature-dependence of the fluorescence signal of an extrinsically added dye, SYPRO, using a Roche LightCycler (Layton and Hellinga, 2010, Biochemistry, 49, 10831-41). The total fluorescence intensity, S, is given by

where fp and fu are the fractions of protein in the folded and unfolded states, respectively, and β _Ρ and ¼ _/ the fluorescence baselines of these two states. To get the fractions of the two states, we have

^N \+K _V (T) ^{U N}

where Ku(T) is the temperature-dependent unfolding equilibrium constant, which by the van't Hoff approximation is given by

K _v = e ^{lr T} - ^}l 13 where T is the temperature, T _m , the unfolding reaction transition mid-point temperature, and AH[ _/ the enthalpy of unfolding.

To obtain the temperature dependence of the binding reaction, the K _& values of all the individually determined isotherms were fit the Gibbs-Hemholtz equation(Layton and

Hellinga, 2010, Biochemistry, 49, 10831-41):

where AG _B ' (τ) is the standard free energy of binding at 1 M ligand at temperature T,

A ^REF H _B ' and A^^the molar enthalpy and entropy of binding, respectively, at the reference temperature, T _re f, and AC _P; the heat capacity of the binding reaction. This data analysis was carried out using 'TitrationMeltAnalysis'.

Structure determination by X-ray crystallography. Sparse-matrix crystallization screens of purified csUBP7 in the presence of 5mM urea were carried out at 17 °C out using the sitting-drop vapor diffusion method. Clusters of thin plates were found in 0.2 M ammonium sulfate, 0.1 M sodium acetate (pH 4.6), 25% polyethylene glycol 4,000. Attorney Docket No. 35327-522001 WO

Individual crystals were obtained from the clusters by dissection and flash frozen in liquid nitrogen following stepwise transfer into a cryoprotectant solution containing 30% additional ethylene glycol. Diffraction data was collected on the ALS synchrotron, using the SIBYLS beamline 12.3.1. The crystals diffracted to 1.8 A resolution. A total of 700 frames were collected with a 0.4° oscillation angle and processed using the XDS program (Kabsch, 2010, Acta Cryst., D66, 125-132). Initial phases were calculated by molecular replacement using the paAmiC poly-alanine structure (Pearl, 1994, EMBO J., 13, 5810-5817; O'Hara, 1999, EMBO J., 18, 5175-5186) as the search model. The data analysis using phenix.triage indicated the presence of translational pseudo-symmetry. Accordingly, the molecular replacement solution was calculated using PHASER (MCCoy, 2007, J. Appl. Cryst., D66, 125-312) with the translation NCS option enabled. The csUBP7 crystal belongs to the P2 ₁ 2 ₁ 2 ₁ space group and contains two molecules in the asymmetric unit with solvent and Matthews coefficient of 0.50 and 2.46 A ³ /Da, respectively. Initial model building and density modification was carried out using the PHENEX. AutoBuild program (Adams, 2010, Acta Crystallogr D Biol Crystallogr, 66, 213-331). Multiple cycles of iterative model building by visual inspection of the electron density maps and refinement calculations (positional, individual B-factor, torsion-angle NCS, stereochemistry weight optimization) were carried out using COOT (Emsley, 2004, Acta Crystallogr D Biol Crystallogr, 60, 2126- 2132) and PHENEX (Adams, 2010, Acta Crystallogr D Biol Crystallogr, 66, 213-331). The electron density for urea was clearly visible in the ligand-binding site in a FoF _c electron density map contoured at 3σ. Solvent was added automatically using phenix.refine and adjusted by manual inspection. The final model i?-factor and i?-free values of 18.67% and 25.58%, respectively. Crystallographic data collection and refinement statistics are show in Table 5.

Mechanisms for Ligand Sensing using Non-Geometric Modulation of ngmFRET.

The subject matter disclosed herein is not limited to or bound by any particular scientific theory. However, discussions regarding ngmFRET are provided to facilitate the understanding of possible mechanisms involved with ngmFRET signaling in various embodiments described herein. Equations for calculating various values mentioned herein are also provided.

The total signal, S, of a fluorescent sensor (either single-wavelength emission intensities, , or ratios of intensities at two wavelengths, i? ₁₂ ) is the sum of the fluorescence due to the ligand-free (apo) and ligand-bound states: Attorne Docket No. 35327-522001 WO

where a and β are the fluorescent baselines in the ligand-free and -bound states, respectively, and y is the fractional occupancy of the binding sites (equation 3).

Fluorescence quantum yields are the fractions of photons emitted by the excited state relative to the total absorbed, and correspond to the ratio of the radiative decay rate relative to the sum of the rates of all possible decay pathways (FIG. 16). For a single fluorophore:

K _r + K _nr

where k _r and k _m are the radiative and non-radiative decay rates of the excited state, respectively. If we define q as the ratio between the radiative and non-radiative decay rates, q = e- 18

K

then the quantum yield can be written as

Q =— 19 q + \

Chemical sensors exploit the ligand-mediated shift of a fluorescent system between the ligand-free and ligand-bound states which each exhibit distinct quantum yields:

Q _obs = Q _aP o( ¹ - y) ⁺ Qsa _t y 20 where Q ₀ b _s , Q _apo and Q _sat are the quantum yield of the total system, the apo-protein, and the ligand-bound complex, respectively. In a system involving ngmFRET between a donor and acceptor fluorophore, the Q _avo and Q _sat quantum yields each are combinations of their respective donor and acceptor quantum yields:

where the superscripts D and A indicate donor and acceptor fluorophores respectively. To understand ngmFRET-based sensors, we therefore need to examine the factors that affect each of these four quantum yields.

The rate of energy transfer, k _t , along a non-radiative pathway between donors and acceptors is a fraction of the donor radiative emission pathway rate (by itself and regardless of the presence of any other fluorophore/parter), ^D k _r (the emission rate in the absence of an acceptor) multiplied by the energy transfer coupling factor, <jr.

k _t = <pQ _D ^D K 22 Attorney Docket No. 35327-522001 WO where Qo is the donor quantum yield in the absence of an acceptor. According to the Forster model of weakly coupled oscillators (Lakowicz, 2006, Principles of fluorescence

spectroscopy. Springer, New York; Valeur, 2012, Molecular Fluorescence. Principles and Applications. Weinheim: Wiley), the energy transfer coupling factor is dependent on the spectral overlap, J, of the donor emission, °λ _ε , _η , and acceptor excitation spectrum, ^Α λ _εχ , and the variation of the geometry, G, between the donor and acceptor excited state transition dipoles with distance, r, and orientation factor, κ.

H \ T(D I A , \ 9000 In 10 „ where

_2

^~ 6 24 and

with n the refractive index of medium, NA Avogrado's number, F(° _EM ) the normalized donor emission spectrum, and ε^λ^) the absorption coefficient of the acceptor excitation spectrum [this analysis is a re-arrangement of the traditional presentation of the equations describing tgmFRET, separating the different contributions (geometry, spectral overlap, quenching)].

At steady state, the concentration of the donor excited state, [£> ^* ], is given by the following rate balance equation (see FIG. 16A) and applying equations 5 and 8:

N _Q ak _a -[D ^* l ^D k _nr+ % + k _t )= N ₀ ak _ex -[ _D ^* fk _nr (l ₊ d + ^ 26 where No is the population of ground state fluorophores, k _ex the rate of excitation photon absorption, a the effective illumination, and d the ratio between the radiative and non- radiative decay rates (analogous to equation 4). Hence

The intensity of the emitted donor light, ID, is

N ₀ ak.

\ + d +

l + d Attorney Docket No. 35327-522001 WO

The donor quantum yield, QD, is this emission intensity relative to the intensity of the excitation, &e _X aNo

The rate balance equation for the acceptor excited state concentration, [A*], is given by Conse uently, by applying equations 5, 8 and 13, the acceptor quantum yield, QA, is

where a is the ratio of the radiative and non-radiative pathways in the acceptor. The ratio of the acceptor and donor quantum yields therefore is

In ngmFRET-based systems, chemical sensing therefore arises from ligand-mediated changes in the rates of the emissive pathway of the donor or acceptor fluorophore and the ngmFRET between them (FIG. 16A). These are affected by the ligand-mediated modulation of the directly responsive partner (DRP) by altering the ratio of radiative and non-radiative decay rates (this "quenching" effect alters the d or a parameters if the DRP functions as donor or acceptor, respectively, equations 29 and 31), and the energy transfer coupling factor, φ, that modulates its resonance with the indirectly responsive partner. A change in any of these three parameters alters the ratio of the donor and acceptor quantum yields (equation 32), thereby enabling ratiometry.

Ligand-mediated donor DRP quenching affects the quantum yields of both the donor, Qo, and acceptor, QA, quantum yields (equations 29, 31). Quenching of an acceptor DRP alters only QA (equation 31).

Changes in affect quantum yields of both fluorophores, regardless whether the DRP functions as the donor or acceptor (equations 23-25, 29, 31). For systems in which there is no ligand-mediated change in the (average) distance between the two fluorophores, changes only if the DRP switches between two different excited state populations ("dipole switching") in response to ligand binding and if the two excited states differ in their spectral properties (emission for donor DRPs; absorption for acceptor DRPs). Excited state dipoles usually also Attorney Docket No. 35327-522001 WO differ in their dipole orientations, so it is likely that changes in spectral overlap involve (reorientation effects. They are also likely to differ in the relative rates of their radiative and non-radiative decay rates. Dipole switching therefore is likely to involve a combination of changes in ngmFRET and quenching effects.

There are eight possible combinations of ligand-mediated changes in quenching and ngmFRET parameters, which have different outcomes on the two emission intensities and their ratio, depending on whether the DRP is the donor or acceptor. The qualitative behavior of the resulting sixteen possibilities in ngmFRET systems are shown in Table 12. Twelve of these have a predictable outcome on the direction of change in the ratio of the two emission intensities. The effect on the direction of change for both donor and acceptor emission intensities can be predicted for seven models. For the other models, the direction of change of one or both peaks depends on the size of the change in the underlying parameters. Purely geometric effects (changes in inter-dipole distance or orientation) always result in anti- correlated changes in emission intensity changes (i.e. one increases and the other decreases, or vice versa). Correlated (i.e both intensities increase or decrease) or uncorrelated (one changes, the other remains constant) intensity changes therefore are prima facie evidence for an ngmFRET effect.

EXAMPLE 11. UREA BIOSENSORS AND USES THEREOF

Urea-binding proteins have been identified accurately using a bioinformatics search strategy that combines genetic linkage and protein structural information. The X-ray structure of a thermostable urea-binding protein from Caldicellulosiruptor saccharolyticus (csUBP7) has been determined to 1.8 A resolution. csUBP7 has been successfully engineered into a ratiometric, reagentless fluorescent urea biosensor, capable of monitoring urea concentrations over four orders of magnitude, including the clinical reference range. This range can be extended to six orders of magnitude by judicious combinations of fiuorophore conjugate and affinity tuning mutations. Ratiometric sensors were constructed using singly labeled conjugates that undergo ligand-mediated shifts in the shape and intensities of their emission spectra, and by incorporating monochromatically responding fiuorophores into dually labeled systems that exploit non-geometrically modulated fluorescence energy transfer (ngmFRET). One of the ngmFRET systems exploits the response of Alexa532 which changes in intensity through an unexpected mechanism involving exchange between dark and fluorescent excited states. Attorney Docket No. 35327-522001 WO

The urea biosensors reported here have utility in point-of-care devices for clinical and on-site environmental chemistry. They may also be incorporated into continuous monitoring instrumentation for clinical as well as environmental, food and beverage production and storage, and/or industrial applications.

The urea sensors probided herein can be incorporated into point-of-care clinical devices to measure urea concentrations accurately, and rapidly at the patient bedside. In a non-limiting example of such a device, a small blood sample (< 10 μΐ.) maybe obtained by means of a finger stick using, e.g., a lancet. This sample droplet is then placed on the aperture of a disposable cartridge containing desiccated, immobilized urea sensors inside a small measurement chamber. The sample enters the chamber by virtue of passive capillary action, wetting the sensors upon contact. As soon as the sensors have been wetted, they bind urea, and report on its concentration by virtue of the engineered fluorescent sensor mechanism. The cartridge is placed inside a small reader (handheld or on a desktop), and their fluorescence signal is measured by the (inexpensive) optoelectronic components of the reader. Excitation light is provided by a light-emitting diode (LED). In the case of

Acrylodan or Badan, a commercially available 400 nm blue LED is used, and the emitted light is measured through two bandpass filters. Cartridges can contain multiple sensors, spanning the entire clinical range of possible urea concentrations. Each sensor is immobilized at a particular, known location inside the cartridge, providing "spatial addressability". The intensity at a particular wavelength is then recorded by imagining these sensors using an inexpensive camera, such as a Complementary metal-oxide semiconductor (CMOS) device commonly found in consumer electronics such as cell phones. Each pixel in the camera records the emitted light on a gray scale. Integration of that signal imaged through the two signals, is analyzed by an on-board computer to calculate the ratiometric signal for each immobilized sensor. Pre-recorded hyperbolic binding curves are then used to calculate the urea concentration in the sample. Recording through multiple sensors, tuned for accurate detection at different urea concentrations provides a high-accuracy reading. This process is completed in less than a minute.

Similar instrumentation can be used for any type of episodic measurements, for instance, using other bodily fluids, or samples obtained from animals, or non-biological samples such as foods and beverages.

The FRS urea sensors also can be used to monitor urea levels continuously. For instance, sensors can be immobilized at the tip of a thin optical fiber to construct a urea- Attorney Docket No. 35327-522001 WO responsive optode. Such an optode can be introduced into the body subcutaneously, using a small needle. Excitation and emission light are passed to and from the immobilized sensor, respectively. The sensor is in continuous contact with the sample. Fluctuations in the urea sample alter the dynamic equilibrium between the open and closed states of the urea-binding protein, which is transduced into fluctuations of the fluorescent emission signal, by virtue of the sensing mechanism of the conjugated fluorophore. The emitted light intensities are read through filters by a reader connected to the optode. This reader continuously displays the change in signal, and the corresponding calculated urea concentrations. Continuous urea monitoring accomplished using a device containing the immobilized urea biosensor(s), e.g., a fiber optic biosensor, introduced into the subject intradermally or subcutaneously (Judge et al., 2011, Diabetes Technology & Therapeutics 13 (3):309-317; Weidemaier et al., 2011, Biosensors and Bioelectronics 26:4117-4123; hereby incorporated by reference).

As was discussed above, the features that distinguish the described constructs, devices, and methods from earlier urea assay systems include:

• Self-calibration

• Rapid response time

• Simple sample-handling fluidic circuitry

• No additional components/substrates ("reagentless")

• No incubation time to develop signal. Reading is near-instantaneous and continuous

• Stability (simplifies manufacturing, distribution, storage)

• Small sample volume (<10 μΐ,).

• Capable of precise measurements over extended urea concentration range (from the hypouremia (e.g., a concentration of less than about 2mM in the blood) to the hyperuremia range (e.g., a concentration of more than about 7mM in the blood).

• Multiple sensors also provides redundancy, lowering error

• Large scope of uses: episodic, continuous, ex vivo, in vivo, optodes, implants. Attorney Docket No. 35327-522001 WO

OTHER EMBODIMENTS

While the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

The patent and scientific literature referred to herein establishes the knowledge that is available to those with skill in the art. All United States patents and published or unpublished United States patent applications cited herein are incorporated by reference. All published foreign patents and patent applications cited herein are hereby incorporated by reference. Genbank and NCBI submissions indicated by accession number cited herein are hereby incorporated by reference. All other published references, documents, manuscripts and scientific literature cited herein are hereby incorporated by reference.

While this invention has been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims.