A Simple and Efficient Docking Method to the Cyclin-Dependent Kinase 2

摘要

The subtle but significant differences and thereby the lack of consensus in active site structures among the crystal structures of cyclin-dependent kinase 2 (CDK2) has hampered structure-based drug design.In this study,we devised a simple but effective 'mutation,pharmacophore-guided docking,followed by mutation' strategy to generate an "average" CDK2 structure,which was used for ligand docking study to successfully reproduce 30 out of 32 X-ray ligand positions within 2.0 A of heavy atom RMSD.This novel docking method was applied for structure-based 3D QSAR with CoMSIA study of a series of structurally related ligands,which showed a good discrimination between CDK2 binders and nonbinders.