Molecular docking studies and comparative binding mode analysis of FDA approved HIV protease inhibitors

Abstract

The HIV protease enzyme (maturation enzyme) is one of the most promising therapeutic targets for the treatment of AIDS. Due to the mutation in the virus, there is always room for new agents. In the present study, in silico molecular docking study was carried to analyze and compare the binding mode of nine FDA approved HIV protease inhibitors as well as to understand their structural requirements to inhibit the enzyme by employing the Glide module of Schrodinger software. Prime MM-GBSA approach was used to study the free energy of binding of these inhibitors with the enzyme. QikProp module of Schrodinger was used to predict the ADME properties of study compounds to evaluate their drug likeness. Binding mode analysis shows that the active site is present at the interface of two chains (A and B) of the enzyme and the crucial amino acid residues responsible for the binding of inhibitors to the HIV-1 protease are found to be Asp25, Gly27, Ala28, Asp29 and Gly49, respectively. Also the ADME properties predicted was found to be in ranges predicted by QikProp module of Schrodinger software for 95% of the known oral drugs. Results of this comparative binding mode analysis of all the FDA approved drugs could be potential and useful for the design of new potent inhibitors of HIV-1 protease.