Binding insight of anti-HIV phytocompounds with prime targets of HIV: A molecular dynamics simulation analysis

Background: Despite intense efforts, AIDS is difficult to tackle by current anti-retroviral therapy (ART) due to its side effects; therefore, there is an urgent need to discover potential, multi-target and low-cost anti-HIV compounds. Objective: We have shown that few phytocompounds can potentially inhibit the prime targets of HIV namely GP120 envelope protein, reverse transcriptase, protease, integrase and ribonulcease. In this study, top ranked prioritized compounds were subjected to Molecular Dynamics (MD) simulation in order to study the conformational dynamics and integrity of crucial interaction in the receptor sites. Methods: The system was built for selected protein-ligand complex using TIP3P water model and OPLS_2005 force field. Trajectories were recorded up to 20 ns simulation time in Desmond module of Schrödinger software. Results: As a result of a comprehensive analysis of molecular properties and dynamics of the complexes, it has been concluded that Chebulic acid, Curcumin and Mulberroside C could be developed as envelope glycoprotein GP120 inhibitor, reverse transcriptase inhibitor and protease inhibitor respectively. However, the fluctuation of Chebulic acid with respect to integrase and ribonuclease protein was higher during the simulation. Conclusion: These findings can aid in the designing of the structural properties for more effective anti-HIV compounds against the given targets.