Reversible peptide folding in solution by molecular dynamics simulation.

Long-standing questions on how peptides fold are addressed by the simulation at different temperatures of the reversible folding of a peptide in solution in atomic detail. Molecular dynamics simulations correctly predict the structure that is thermodynamically stable at 298 K, irrespective of the initial peptide conformation. The rate of folding and the free energy of folding at different temperatures are estimated. Although the conformational space potentially accessible to the peptide is extremely large, very few conformers (10(1) to 10(2)) are significantly populated at 20 K above the melting temperature. This implies that the search problem in peptide (or even protein) folding is surmountable using dynamics simulations.