To provide a method for engineering and optimizing based on the sequence of a single chain antibody.

Provided are methods of using sequence-based analysis and rational strategies to modify and improve structural and biophysical properties of single chain antibodies (ScFvs) including stability, solubility and antigen binding affinity. These methods and strategies can be used individually or in combination. The methods also include the use of a database comprising scFv sequences from an experimentally screened scFv library of antibodies that have been selected to have superior solubility and stability. The invention also provides methods of using the properties found for these selected antibodies in a general approach for reshaping scFv antibodies to improve their stability and solubility properties.