3D-QSAR for CDK2 inhibitors using the fragment binding energy obtained by FMO method

Abstract

We developed a 3D-QSAR model for CDK2 inhibitors using protein-ligand docking, fragment molecular orbital (FMO) method and PLS regression. In order to obtain reliable complex structures, each inhibitor with known activity was docked to the protein structure prepared from the X-ray structure of protein complexed with the most similar ligand. Then, fragment binding energies upon ligand binding were calculated using FMO method. Finally, using the fragment binding energies as descriptors, a PLS regression model for predicting inhibitory activity was developed and validated. The 3D-QSAR model was able to predict the experimental activity for a variety of CDK2 inhibitors with broad activity.