TCB Publications - Abstract

TCB Publications - Abstract

Peter L. Freddolino and Klaus Schulten. Common structural transitions in explicit-solvent simulations of villin headpiece folding. Biophysical Journal, 97:2338-2347, 2009. (PMC: 2764099)

FRED2009A Molecular dynamics simulations of protein folding can provide very high resolution data on the folding process; however, due to computational challenges most studies of protein folding have been limited to small peptides, or made use of approximations such as Go potentials or implicit solvent models. We have performed a set of molecular dynamics simulations totaling over 50 microseconds on the villin headpiece subdomain, one of the most stable and fastest-folding naturally occurring proteins, in explicit solvent. We find that the wild type villin headpiece reliably folds to a native conformation on timescales similar to experimentally observed folding, but that a fast folding double-norleucine mutant shows significantly more heterogeneous behavior. Along with other recent simulation studies, we note the occurrence of non-native structures which may yield a native-like signal in the fluorescence measurements typically used to study villin folding. Based on the wild type simulations we propose alternative approaches to measure the formation of the native state.

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