title: Reproducible polypeptide folding and structure prediction using molecular dynamics simulations.
abstract: The folding of a polypeptide from an extended state to a well-defined conformation is studied using microsecond classical molecular dynamics (MD) simulations and replica exchange molecular dynamics (REMD) simulations in explicit solvent and in vacuo. It is shown that the solvated peptide folds many times in the REMD simulations but only a few times in the conventional simulations. From the folding events in the classical simulations we estimate an approximate folding time of 1-2 micros. The REMD simulations allow enough sampling to deduce a detailed Gibbs free energy landscape in three dimensions. The global minimum of the energy landscape corresponds to the native state of the peptide as determined previously by nuclear magnetic resonance (NMR) experiments. Starting from an extended state it takes about 50 ns before the native structure appears in the REMD simulations, about an order of magnitude faster than conventional MD. The calculated melting curve is in good qualitative agreement with experiment. In vacuo, the peptide collapses rapidly to a conformation that is substantially different from the native state in solvent.
authors.affiliation: Department of Mathematical Sciences, Chalmers University of Technology, SE41296 Gothenberg, Sweden.
authors.forename: M Marvin
authors.initials: MM
authors.lastname: Seibert
authors.forename: Alexandra
authors.initials: A
authors.lastname: Patriksson
authors.forename: Berk
authors.initials: B
authors.lastname: Hess
authors.forename: David
authors.initials: D
authors.lastname: van der Spoel
mesh_terms: D003198:Computer Simulation; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009930:Organic Chemicals / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D015203:Reproducibility of Results; D012997:Solvents; D013696:Temperature; D013816:Thermodynamics; D014618:Vacuum
chemical_list: D009930:Organic Chemicals; D010455:Peptides; D012997:Solvents; C016088:quinolytin