Comparative Analysis of Various Electrostatic Potentials on Docking Precision Against Cyclin‐Dependent Kinase 2 Protein: A Multiple Docking Approach

The fundamental of molecular modeling is the interaction and binding to form a complex, because it explains the action of most drugs to a receptor active site. In the present study, different semiempirical ( RM 1, AM 1, PM 3, MNDO ) and ab intio ( HF , DFT ) charge models were investigated for their performance in prediction of docking pose against CDK 2 proteins with their respective inhibitor. Further, multiple docking approaches and Prime/ MM ‐ GBSA calculations were applied to predict the binding mode with respective charge model against CDK 2 inhibitors. A reliable docking result was obtained using RRD , which showed significance improvement on ligand binding poses and docking score accuracy to the IFD . The combined use of RRD and Prime/ MM ‐ GBSA method could give a high correlation between the predicted binding free energy and experimental biological activity. The preliminary results point out that AM 1 could be a precious charge model for design of new drugs with enhanced success rate. As a very similar result was also found for a different system of the protein–ligand binding, the suggested scoring function based on AM 1 method seems to be applicable in drug design. The results from this study can provide insights into highest success rate for design of potent and selective CDK 2 inhibitors.