G.M.S. De Mori, C. Micheletti and G. Colombo
Simulations of the Villin Headpiece from Stochastically Selected
J. Phys. Chem. B 108 12267-12270 (2004).
Link to online article.
We discuss the application of a novel efficient protocol for the
numerical simulation of the folding dynamics of single domain proteins
from the only knowledge of primary sequence. Our approach is based on
the combination of a Monte Carlo (MC) coarse-grained evolution
followed by all-atom molecular dynamics (MD) simulations in explicit
solvent. The coarse-grained model simplifies the protein's energy
landscape and allows it to evolve rapidly toward viable starting
conformations for MD. A general fine-graining algorithm is then used
to reconstruct the full atomic detail of the protein. All atom MD
simulations in explicit water are then employed to investigate the
protein's conformational evolution toward the native state. We discuss
the application of this novel approach to the Villin headpiece, a
widely studied test system for folding studies, for which we obtain
and maintain an RMS deviation from the NMR structure of 2.4 Å for
the core region and 3.7 Å for the whole protein. Finally, the
analysis of the MC-MD trajectories provides valuable insight into
important aspects of the folding process with regards to the
appearance and docking of locally secondary structure elements.