Structural and Energetic Analysis on the Complexes of Clinically Isolated Subtype C HIV-1 Proteases and Approved Inhibitors by Molecular Dynamics Simulation

HIV-1 has a large genetic diversity. Subtype 13 HIV-1 is commonly found in patients in developed countries. In contrast, all increasing number of patients are infected with the non-B Subtype Viruses, especially with Subtype C HIV-1, in developing Countries. It remains to be clarified how mutations or polymorphisms in non-B Subtype HIV-1 influence the efficacy of the approved inhibitors. In this Study, we have performed molecular dynamics Simulations on clinically isolated subtype C HIV-1 proteases in complex with three kinds of approved inhibitors. From the structural and energetic viewpoints, we identified the polymorphisms influencing oil the binding of the inhibitors. The effect of the V821 Mutation Oil the association with chemicals and the reason for rare appearance of the D30N mutation in subtype C HIV-1 were discussed in terms of the change of geometry of the residues in HIV-1 protease.