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