SELECTION OF BEST CRYSTAL STRUCTURE FOR INITIATING DOCKING-BASED VIRTUAL SCREENING STUDIES OF CDK2 INHIBITORS: A CROSS-DOCKING AND DUD SET VALIDATION APPROACH

Abstract

A total of 95 crystal structures of CDK2 were selected after considering criteria such as resolution and absence of missing residues in the active site; and subjected to cross-docking. 14 out of 95 crystal structures exhibited docking accuracy for greater than 70% of ligands at RMSD cut off 2Å in the cross- docking studies. These 14 crystal structures were selected for the second part of the study, which included validation using DUD sets and enrichment calculations. 8 out of 14 crystal structures possessed the enrichment factor of >10 at 1% of the ranked database. ROC-AUC, AUAC, RIE, and BEDROC were calculated for these 8 crystal structures. 2WXV produced maximum BEDROC (0.768, at α=8) and RIE (11.22). 2WXV as a single initial crystal structure in the virtual screening protocol is likely to produce more accurate results than any other single crystal structure.