Dynamical basis for drug resistance of HIV-1 protease.

ABSTRACT:

Background

Protease inhibitors designed to bind to protease have become major anti-AIDS drugs. Unfortunately, the emergence of viral mutations severely limits the long-term efficiency of the inhibitors. The resistance mechanism of these diversely located mutations remains unclear.

Results

Here I use an elastic network model to probe the connection between the global dynamics of HIV-1 protease and the structural distribution of drug-resistance mutations. The models for study are the crystal structures of unbounded and bound (with the substrate and nine FDA approved inhibitors) forms of HIV-1 protease. Coarse-grained modeling uncovers two groups that couple either with the active site or the flap. These two groups constitute a majority of the drug-resistance residues. In addit

SUBMITTER: Mao Y 

PROVIDER: S-EPMC3149572 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature