Multiple routes and milestones in the folding of HIV-1 protease monomer.

ABSTRACT: Proteins fold on a time scale incompatible with a mechanism of random search in conformational space thus indicating that somehow they are guided to the native state through a funneled energetic landscape. At the same time the heterogeneous kinetics suggests the existence of several different folding routes. Here we propose a scenario for the folding mechanism of the monomer of HIV-1 protease in which multiple pathways and milestone events coexist. A variety of computational approaches supports this picture. These include very long all-atom molecular dynamics simulations in explicit solvent, an analysis of the network of clusters found in multiple high-temperature unfolding simulations and a complete characterization of free-energy surfaces carried out using a structure-based potential at

SUBMITTER: Bonomi M 

PROVIDER: S-EPMC2954147 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature