title: Protein folding kinetics and thermodynamics from atomistic simulations.
abstract: Determining protein folding kinetics and thermodynamics from all-atom molecular dynamics (MD) simulations without using experimental data represents a formidable scientific challenge because simulations can easily get trapped in local minima on rough free energy landscapes. This necessitates the computation of multiple simulation trajectories, which can be independent from each other or coupled in some manner, as, for example, in the replica exchange MD method. Here we present results obtained with a new analysis tool that allows the deduction of faithful kinetics data from a heterogeneous ensemble of simulation trajectories. The method is demonstrated on the decapeptide Chignolin for which we predict folding and unfolding time constants of 1.0 +/- 0.3 and 2.6 +/- 0.4 micros, respectively. We also derive the energetics of folding, and calculate a realistic melting curve for Chignolin.
authors.affiliation: Department of Cellular and Molecular Biology, Biomedical Centre, Box 596, Uppsala University, SE-75124 Uppsala, Sweden. spoel@xray.bmc.uu.se
authors.forename: David
authors.initials: D
authors.lastname: van der Spoel
authors.forename: M Marvin
authors.initials: MM
authors.lastname: Seibert
mesh_terms: D003198:Computer Simulation; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D011506:Proteins