Structural Characterization of ?-Repressor Folding from All-Atom Molecular Dynamics Simulations.

ABSTRACT: The five-helix bundle ?-repressor fragment is a fast-folding protein. A length of 80 amino acid residues puts it on the large end among all known microsecond folders and its size poses a computational challenge for molecular dynamics (MD) studies. We simulated the folding of a novel ?-repressor fast-folding mutant (?-HG) in explicit solvent using an all-atom description. By means of a recently developed tempering method, we observed reversible folding and unfolding of ?-repressor in a 10-microsecond trajectory. The folding kinetics was also investigated through a set of MD simulations run at different temperatures that together covered more than 125 microseconds. The protein was seen to fold into a native-like topology at intermediate temperature and a slow-folding pathway was identified. The simulations suggest new experimental observables for better monitoring the folding process, and a novel mutation expected to accelerate ?-repressor folding.

SUBMITTER: Liu Y 

PROVIDER: S-EPMC3377354 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature