3D QSAR pharmacophore based virtual screening and molecular docking for identification of potential HSP90 inhibitors.
Chemical features based 3D pharmacophore models were developed for HSP90 based on the known inhibitors using Discovery Studio V2.1. An optimal pharmacophore model was brought forth and validated using a decoy set, external test set and Fischer's randomization method. The best five features pharmacophore model, Hypo1, includes two hydrogen bond acceptors, three hydrophobic features, which has the highest correlation coefficient (0.93), cost difference (73.88), low RMS (1.24), as well as it shows a high goodness of fit and enrichment factor. Hypo1 was used as a 3D query for virtual screening to retrieve potential inhibitors from Maybridge and Scaffold databases. The hit compounds were subsequently subjected to molecular docking studies and finally, 36 compounds were obtained based on consensus scoring function.
Sakkiah
Sugunadevi
S
Division of Applied Life Science (BK21 Program), Environmental Biotechnology National Core Research Center (EB-NCRC), Gyeongsang National University, Jinju 660-701, Republic of Korea.
Thangapandian
Sundarapandian
S
John
Shalini
S
Kwon
Yong Jung
YJ
Lee
Keun Woo
KW
D004353:Drug Evaluation, Preclinical / Q000379:methods*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008968:Molecular Conformation; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D014584:User-Computer Interface
D018841:HSP90 Heat-Shock Proteins; D054852:Small Molecule Libraries