Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism.

ABSTRACT: Inhibitors of HIV-1 protease (HIV-1-pr) generally only bind to the active site of the protease. However, for some mutants such as V32I and M46L the TMC114 can bind not only to the active cavity but also to the groove of the flexible flaps. Although the second binding site suggests the higher efficiency of the drug against HIV-1-pr, the drug resistance in HIV-1-pr due to mutations cannot be ignored, which prompts us to investigate the molecular mechanisms of drug resistance and behavior of double bound TMC114 (2T) to HIV-1-pr. The conformational dynamics of HIV-1-pr and the binding of TMC114 to the WT, V32I and M46L mutants were investigated with all-atom molecular dynamic (MD) simulation. The 20 ns MD simulation shows many fascinating effects of the inhibitor binding to the WT and mutant p

SUBMITTER: Meher BR 

PROVIDER: S-EPMC4314403 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature