Prediction and comparison of hiv-1 protease inhibitor binding energies by various molecular docking methods

Abstract

The human immunodeficiency virus type 1 Aspartic protease (HIV-1 PR) is an important enzyme due to its vital role in viral maturation. Inactivation of the enzyme causes the production of immature viral particles. The accurate prediction of enzymesubstrate interaction energies is one of the major challenges in computational biology. Docking experiments were undertaken using the programs AutoDock.4 and online programs pardock for twenty-five HIV-1 protease-inhibitor complexes determined by x-ray crystallography. From the molecular docking study, we were able to select a best solution based on lowest binding energy and lowest RMSD values of receptor-ligand complex in each docking program.Correlations observed for experimental and predicted binding energy values for receptor-ligand complex. A highest correlation coefficient of 0.801 was observed between the experimental and predicted binding energy for pardock program and 0.484 by autodock 4.0. Patch dock followed by firedock methods also used to predict the global energy of each enzyme-inhibitor complex and complementarily score. Our result indicates that the binding energies predicted by pardock program are highly correlated with experimental binding energies. The consensus ranking of enzyme-inhibitor complexes in various molecular docking methods improve the binding energy predictions. Consensus ranking has become an important method in various molecular docking methods to identify new inhibitors in computer-assisted discovery of new pharmaceutics.