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 (RM1, AM1, PM3, MNDO) and ab initio (HF, DFT) charge models were investigated for their performance in prediction of docking pose against CDK2 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 CDK2 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 AM1 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 AM1 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 CDK2 inhibitors.
['Tripathi|Sunil K|SK|', 'Soundarya|Rajendran Naga|RN|', 'Singh|Poonam|P|', 'Singh|Sanjeev K|SK|']
D000255:Adenosine Triphosphate D001665:Binding Sites D051357:Cyclin-Dependent Kinase 2 D015195:Drug Design D006801:Humans D062105:Molecular Docking Simulation D011485:Protein Binding D047428:Protein Kinase Inhibitors D055672:Static Electricity D013816:Thermodynamics
MM-GBSA QM/MM docking ab initio method atomic charges semiempirical method