Strength of hydrogen bond network takes crucial roles in the dissociation process of inhibitors from the HIV-1 protease binding pocket.

ABSTRACT: To understand the underlying mechanisms of significant differences in dissociation rate constant among different inhibitors for HIV-1 protease, we performed steered molecular dynamics (SMD) simulations to analyze the entire dissociation processes of inhibitors from the binding pocket of protease at atomistic details. We found that the strength of hydrogen bond network between inhibitor and the protease takes crucial roles in the dissociation process. We showed that the hydrogen bond network in the cyclic urea inhibitors AHA001/XK263 is less stable than that of the approved inhibitor ABT538 because of their large differences in the structures of the networks. In the cyclic urea inhibitor bound complex, the hydrogen bonds often distribute at the flap tips and the active site. In contrast, th

SUBMITTER: Li D 

PROVIDER: S-EPMC3084818 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature