Title:
METHOD FOR EXCAVATING NEW DRUG CANDIDATE TARGETING NONSTRUCTURE-STRUCTURE TRANSITION SITE AND APPARATUS FOR EXCAVATING NEW DRUG CANDIDATE
Document Type and Number:
WIPO Patent Application WO/2018/097635
Kind Code:
A1
Abstract:
A method for excavating a new drug candidate targeting a nonstructure-structure transition site, comprising: a step in which a computer device utilizes bioinformatics to determine a nonstructure-structure transition site of a target protein; a step in which the computer device performs molecular docking to the nonstructure-structure transition site in conjunction with a library of specific compounds to select first candidate compounds capable of binding to the nonstructure-structure transition site from among the compound library; and a step in which the computer device performs molecular dynamics simulation for the first candidate compounds and the nonstructure-structure transition site to select a second candidate compound from among the first candidate compounds.
Inventors:
NA INSUNG (KR)
KIM MIN YOUNG (KR)
UVERSKY VLADIMIR (US)
KIM CHUL GEUN (KR)
KIM MIN YOUNG (KR)
UVERSKY VLADIMIR (US)
KIM CHUL GEUN (KR)
Application Number:
PCT/KR2017/013489
Publication Date:
May 31, 2018
Filing Date:
November 24, 2017
Export Citation:
Assignee:
UNIV HANYANG IND UNIV COOP FOUND (KR)
International Classes:
G01N33/68; G06F19/00; G06F19/12; G06F19/16
Foreign References:
| KR20150008179A | 2015-01-21 | |||
| JP2006252485A | 2006-09-21 | |||
| JP2007272627A | 2007-10-18 | |||
| KR100773055B1 | 2007-11-02 | |||
| KR101400717B1 | 2014-05-29 |
Other References:
SLACK ABOVENZI VBIGEY PIVANOV MARAMCHANDANI SBHATTACHARYA STENOEVER BLAMRIHI BSCHERMAN DSZYF M: "Antisense MBD2 gene therapy inhibits tumorigenesis", J GENE MED, vol. 4, 2002, pages 381, XP008009438, DOI: doi:10.1002/jgm.288
SANSOM OJBERGER JBISHOP SMHENDRICH BBIRD ACLARKE AR: "Deficiency of Mbd2 suppresses intestinal tumorigenesis", NAT GENET, vol. 34, 2003, pages 145
MIAN OYWANG SZZHU SZGNANAPRAGASAM MNGRAHAM LBEAR HDGINDER GD: "Methyl-binding domain protein 2-dependent proliferation and survival of breast cancer cells", MOL CANCER RES, vol. 9, 2011, pages 1152
KANG HCCHAE JHLEE YHPARK MASHIN JH, KIM SHYE SKCHO YSFIERING SKIM CG: "Erythroid cell-specific alpha-globin gene regulation by the CP2 transcription factor family", MOL CELL BIOL, vol. 25, 2005, pages 6005
KANG HCCHAE JHJEON JKIM WHA DHSHIN JHKIM CGKIM CG: "PIAS1 regulates CP2c localization and active promoter complex formation in erythroid cell-specific alpha-globin expression", NUCLEIC ACIDS RES, vol. 38, 2010, pages 5456
KANG HCCHUNG BMCHAE JHYANG SIKIM CGKIM CG: "Identification and characterization of four novel peptide motifs that recognize distinct regions of the transcription factor CP2", FEBS J, vol. 272, 2005, pages 1265, XP055316727, DOI: doi:10.1111/j.1742-4658.2005.04564.x
GNANAPRAGASAM MNSCARSDALE JNAMAYA MLWEBB HDDESAI MAWALAVALKAR NMWANG SZZU ZHU SGINDER GDWILLIAMS DC JR: "p66Alpha- MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2-NuRD complex", PROC NATL ACAD SCI USA, vol. 108, 2011, pages 7487
WALAVALKAR NMGORDON NWILLIAMS DC JR: "Unique features of the anti-parallel, heterodimeric coiled-coil interaction between methyl-cytosine binding domain 2 (MBD2) homologues and GATA zinc finger domain containing 2A (GATAD2A/p66a", J BIOL CHEM, vol. 288, 2013, pages 3419, XP055236750, DOI: doi:10.1074/jbc.M112.431346
YIN XGIAP CLAZO JSPROCHOWNIK EV: "Low molecular weight inhibitors of Myc-Max interaction and function", ONCOGENE, vol. 22, no. 40, 2003, pages 6151 - 9, XP002995346, DOI: doi:10.1038/sj.onc.1206641
FOLLIS AVHAMMOUDEH DIWANG HPROCHOWNIK EVMETALLO SJ: "tructural rationale for the coupled binding and unfolding of the c-Myc oncoprotein by small molecules", CHEMISTRY & BIOLOGY, vol. 15, no. 11, 2008, pages 1149 - 55, XP025678147, DOI: doi:10.1016/j.chembiol.2008.09.011
MICHEL JCUCHILLO R: "The impact of small molecule binding on the energy landscape of the intrinsically disordered protein C-myc", PLOS ONE, vol. 7, 2012, pages e41070
UVERSKY VN: "Intrinsically disordered proteins and novel strategies for drug discovery", EXPERT OPINION ON DRUG DISCOVERY, vol. 7, 2012, pages 475
CELL, vol. 112, no. 2, 2003, pages 193 - 205
GNANAPRAGASAM MNSCARSDALE JNAMAYA MLWEBB HDDESAI MAWALAVALKAR NMWANG SZZU ZHU SGINDER GDWILLIAMS DC JR: "p66Alpha-MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2-NuRD complex", PROC NATL ACAD SCI USA, vol. 108, 2011, pages 7487
SANSOM OJBERGER JBISHOP SMHENDRICH BBIRD ACLARKE AR: "Deficiency of Mbd2 suppresses intestinal tumorigenesis", NAT GENET, vol. 34, 2003, pages 145
MIAN OYWANG SZZHU SZGNANAPRAGASAM MNGRAHAM LBEAR HDGINDER GD: "Methyl-binding domain protein 2-dependent proliferation and survival of breast cancer cells", MOL CANCER RES, vol. 9, 2011, pages 1152
KANG HCCHAE JHLEE YHPARK MASHIN JH, KIM SHYE SKCHO YSFIERING SKIM CG: "Erythroid cell-specific alpha-globin gene regulation by the CP2 transcription factor family", MOL CELL BIOL, vol. 25, 2005, pages 6005
KANG HCCHAE JHJEON JKIM WHA DHSHIN JHKIM CGKIM CG: "PIAS1 regulates CP2c localization and active promoter complex formation in erythroid cell-specific alpha-globin expression", NUCLEIC ACIDS RES, vol. 38, 2010, pages 5456
KANG HCCHUNG BMCHAE JHYANG SIKIM CGKIM CG: "Identification and characterization of four novel peptide motifs that recognize distinct regions of the transcription factor CP2", FEBS J, vol. 272, 2005, pages 1265, XP055316727, DOI: doi:10.1111/j.1742-4658.2005.04564.x
GNANAPRAGASAM MNSCARSDALE JNAMAYA MLWEBB HDDESAI MAWALAVALKAR NMWANG SZZU ZHU SGINDER GDWILLIAMS DC JR: "p66Alpha- MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2-NuRD complex", PROC NATL ACAD SCI USA, vol. 108, 2011, pages 7487
WALAVALKAR NMGORDON NWILLIAMS DC JR: "Unique features of the anti-parallel, heterodimeric coiled-coil interaction between methyl-cytosine binding domain 2 (MBD2) homologues and GATA zinc finger domain containing 2A (GATAD2A/p66a", J BIOL CHEM, vol. 288, 2013, pages 3419, XP055236750, DOI: doi:10.1074/jbc.M112.431346
YIN XGIAP CLAZO JSPROCHOWNIK EV: "Low molecular weight inhibitors of Myc-Max interaction and function", ONCOGENE, vol. 22, no. 40, 2003, pages 6151 - 9, XP002995346, DOI: doi:10.1038/sj.onc.1206641
FOLLIS AVHAMMOUDEH DIWANG HPROCHOWNIK EVMETALLO SJ: "tructural rationale for the coupled binding and unfolding of the c-Myc oncoprotein by small molecules", CHEMISTRY & BIOLOGY, vol. 15, no. 11, 2008, pages 1149 - 55, XP025678147, DOI: doi:10.1016/j.chembiol.2008.09.011
MICHEL JCUCHILLO R: "The impact of small molecule binding on the energy landscape of the intrinsically disordered protein C-myc", PLOS ONE, vol. 7, 2012, pages e41070
UVERSKY VN: "Intrinsically disordered proteins and novel strategies for drug discovery", EXPERT OPINION ON DRUG DISCOVERY, vol. 7, 2012, pages 475
CELL, vol. 112, no. 2, 2003, pages 193 - 205
GNANAPRAGASAM MNSCARSDALE JNAMAYA MLWEBB HDDESAI MAWALAVALKAR NMWANG SZZU ZHU SGINDER GDWILLIAMS DC JR: "p66Alpha-MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2-NuRD complex", PROC NATL ACAD SCI USA, vol. 108, 2011, pages 7487
Attorney, Agent or Firm:
ISIS IP LAW LLC (KR)
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