Evaluating the potency of HIV-1 protease drugs to combat resistance.

ABSTRACT: HIV-1 protease has been an important drug target for the antiretroviral treatment of HIV infection. The efficacy of protease drugs is impaired by the rapid emergence of resistant virus strains. Understanding the molecular basis and evaluating the potency of an inhibitor to combat resistance are no doubt important in AIDS therapy. In this study, we first identified residues that have significant contributions to binding with six substrates using molecular dynamics simulations and Molecular Mechanics Generalized Born Surface Area calculations. Among the critical residues, Asp25, Gly27, Ala28, Asp29, and Gly49 are well conserved, with which the potent drugs should form strong interactions. We then calculated the contribution of each residue to binding with eight FDA approved drugs. We analyze

SUBMITTER: Hou T 

PROVIDER: S-EPMC2628484 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature