ABSTRACT
Abstract .................................................................................................................360 12.1 Introduction ................................................................................................360 12.2 Materials and Methods ...............................................................................363 12.3 Results and Discussions .............................................................................369 12.4 Conclusions ................................................................................................381 Keywords ..............................................................................................................381 References .............................................................................................................382
A newly designed novel approach of docking based scoring parameters based quantitative structure-activity relationship (QSAR) model was developed on a 37 compounds of bisphenylbenzimidazole analogues. The molecular docking simulation was carried out by GLIDE, GOLD, and AutoDock Vina docking programs. All the calculated docking-based scoring parameters were considered in QSAR model development using linear and nonlinear approaches. The linear approach (simulated-annealing) based QSAR model showed better robustness with cross-validated Q2 of 0.728 and r2pred of 0.634 over nonlinear approach based QSAR model (Q2 of 0.697 and r2pred of 0.603). The developed robust model and approach could be further used as a virtual screening tool to find novel hits for the chosen target. The docking based scoring parameters based QSAR study suggested the importance of hydrophobic substituents, surface area, volume, and flexibility of the ligands. It was also inferred from the present study, that non-nucleoside reverse transcriptase inhibitors should obtain their characteristic butterfly-like orientation for better interaction in the binding pocket of non-nucleoside reverse transcriptase enzyme.
