HIV-1 protease substrate binding and product release pathways explored with coarse-grained molecular dynamics.

ABSTRACT: We analyze the encounter of a peptide substrate with the native HIV-1 protease, the mechanism of substrate incorporation in the binding cleft, and the dissociation of products after substrate hydrolysis. To account for the substrate, we extend a coarse-grained model force field, which we previously developed to study the flap opening dynamics of HIV-1 protease on a microsecond timescale. Molecular and Langevin dynamics simulations show that the flaps need to open for the peptide to bind and that the protease interaction with the substrate influences the flap opening frequency and interval. On the other hand, release of the products does not require flap opening because they can slide out from the binding cleft to the sides of the enzyme. Our data show that in the protease-substrate complex

SUBMITTER: Trylska J 

PROVIDER: S-EPMC1877780 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature