Free-energy-driven folding and thermodynamics of the 67-residue protein GS-alpha3W--a large-scale Monte Carlo study.

Utilizing the computational power of a few thousand processors on a BlueGene/P, we have explored the folding mechanism of the 67-residue protein GS-alpha(3)W. Results from our large-scale simulation indicate a diffusion-collision mechanism for folding. However, the lower-than-expected frequency of native-like configurations at physiological temperatures indicates shortcomings of our energy function. Our results suggest that computational studies of large proteins call for redevelopment and reparametrization of force fields that in turn require extensive simulations only possible with the newly available supercomputers with computing powers reaching the petaflop range. 2009 Wiley Periodicals, Inc.