Protein and peptide folding explored with molecular simulations

Molecular simulations, comprising models with atomic details of polypeptide and solvent as well as minimalist models employing only Calpha atoms, a-re being used with specialized simulation methods from statistical mechanics to examine fundamental questions in peptide and protein folding mechanism, kinetics, and thermodynamics. Detailed calculations of free energy changes along coordinates describing the formation of hydrogen-bonding interactions in helical, turn, and beta-sheet models provide insights into the time scale and mechanism of secondary structure formation. Potential roles for these processes in directing protein folding are also elucidated by such calculations. Analogous methodologies extended to more complex polypeptides with tertiary structures (proteins) are used to explore global questions about protein folding landscapes, to delineate atomic details of folding mechanism, and to elucidate putative roles for solvent in the late stages of folding.