How kinetics within the unfolded state affects protein folding: an analysis based on markov state models and an ultra-long MD trajectory.

ABSTRACT: Understanding how kinetics in the unfolded state affects protein folding is a fundamentally important yet less well-understood issue. Here we employ three different models to analyze the unfolded landscape and folding kinetics of the miniprotein Trp-cage. The first is a 208 μs explicit solvent molecular dynamics (MD) simulation from D. E. Shaw Research containing tens of folding events. The second is a Markov state model (MSM-MD) constructed from the same ultralong MD simulation; MSM-MD can be used to generate thousands of folding events. The third is a Markov state model built from temperature replica exchange MD simulations in implicit solvent (MSM-REMD). All the models exhibit multiple folding pathways, and there is a good correspondence between the folding pathways from direct MD and t

SUBMITTER: Deng NJ 

PROVIDER: S-EPMC3808496 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature