Insights into the dynamics of HIV-1 protease: a kinetic network model constructed from atomistic simulations.

ABSTRACT: The conformational dynamics in the flaps of HIV-1 protease plays a crucial role in the mechanism of substrate binding. We develop a kinetic network model, constructed from detailed atomistic simulations, to determine the kinetic mechanisms of the conformational transitions in HIV-1 PR. To overcome the time scale limitation of conventional molecular dynamics (MD) simulations, our method combines replica exchange MD with transition path theory (TPT) to study the diversity and temperature dependence of the pathways connecting functionally important states of the protease. At low temperatures the large-scale flap opening is dominated by a small number of paths; at elevated temperatures the transition occurs through many structurally heterogeneous routes. The expanded conformation in the crysta

SUBMITTER: Deng NJ 

PROVIDER: S-EPMC3116037 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature