(Un)Folding mechanisms of the FBP28 WW domain in explicit solvent revealed by multiple rare event simulation methods.

ABSTRACT: We report a numerical study of the (un)folding routes of the truncated FBP28 WW domain at ambient conditions using a combination of four advanced rare event molecular simulation techniques. We explore the free energy landscape of the native state, the unfolded state, and possible intermediates, with replica exchange molecular dynamics. Subsequent application of bias-exchange metadynamics yields three tentative unfolding pathways at room temperature. Using these paths to initiate a transition path sampling simulation reveals the existence of two major folding routes, differing in the formation order of the two main hairpins, and in hydrophobic side-chain interactions. Having established that the hairpin strand separation distances can act as reasonable reaction coordinates, we employ metady

SUBMITTER: Juraszek J 

PROVIDER: S-EPMC2820652 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature