PATHWAYS TO A PROTEIN-FOLDING INTERMEDIATE OBSERVED IN A 1-MICROSECOND SIMULATION IN AQUEOUS-SOLUTION

An implementation of classical molecular dynamics on parallel computer s of increased efficiency has enabled a simulation of protein folding with explicit representation of water for 1 microsecond, about two ord ers of magnitude Longer than the Longest simulation of a protein in wa ter reported to date. Starting with an unfolded state of villin headpi ece subdomain, hydrophobic collapse and helix formation occur in an in itial phase, followed by conformational readjustments. A marginally st able state, which has a Lifetime of about 150 nanoseconds, a favorable solvation free energy, and shows significant resemblance to the nativ e structure, is observed; two pathways to this state have been found.