G.M.S. De Mori, G. Colombo and C. Micheletti
Study of the Villin Headpiece folding dynamics by combining
coarse-grained Monte Carlo evolution and all-atom Molecular Dynamics
Proteins 58,459-471 (2005).
Preprint full text (cond-mat archive),
Link to online article.
ABSTRACT
The folding mechanism of the Villin headpiece (HP36) is studied by
means of a novel approach which entails an initial coarse-grained
Monte Carlo (MC) scheme followed by all-atom molecular dynamics (MD)
simulations in explicit solvent. The MC evolution occurs in a
simplified free-energy landscape and allows an efficient selection of
marginally-compact structures which are taken as viable initial
conformations for the MD. The coarse-grained MC structural
representation is connected to the one with atomic resolution through
a ``fine--graining'' reconstruction algorithm. This two-stage strategy
is used to select and follow the dynamics of seven different unrelated
conformations of HP36. In a notable case the MD trajectory rapidly
evolves towards the folded state, yielding a typical RMS deviation of
the core region of only 2.4 A from the closest NMR model (the typical
RMSD over the whole structure being 4.0A). The analysis of the various
MC-MD trajectories provides valuable insight into the details of the
folding and mis-folding mechanisms and particularly about the delicate
influence of local and non-local interactions in steering the folding
process.