title: Toward a unified representation of protein structural dynamics in solution.
abstract: An atomic resolution description of protein flexibility is essential for understanding the role that structural dynamics play in biological processes. Despite the unique dependence of nuclear magnetic resonance (NMR) to motional averaging on different time scales, NMR-based protein structure determination often ignores the presence of dynamics, representing rapidly exchanging conformational equilibria in terms of a single static structure. In this study, we use the rich dynamic information encoded in experimental NMR parameters to develop a molecular and statistical mechanical characterization of the conformational behavior of proteins in solution. Critically, and in contrast to previously proposed techniques, we do not use empirical energy terms to restrain a conformational search, a procedure that can strongly perturb simulated dynamics in a nonpredictable way. Rather, we use accelerated molecular dynamic simulation to gradually increase the level of conformational sampling and to identify the appropriate level of sampling via direct comparison of unrestrained simulation with experimental data. This constraint-free approach thereby provides an atomic resolution free-energy weighted Boltzmann description of protein dynamics occurring on time scales over many orders of magnitude in the protein ubiquitin.
authors.affiliation: Protein Dynamics and Flexibility, Institute de Biologie Structurale Jean-Pierre Ebel, CNRS-CEA-UJF UMR 5075, 41 rue Jules Horowitz, 38027-Grenoble Cedex, France. pmarkwick@ucsd.edu
authors.forename: Phineus R L
authors.initials: PR
authors.lastname: Markwick
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bouvignies
authors.forename: Loic
authors.initials: L
authors.lastname: Salmon
authors.forename: J Andrew
authors.initials: JA
authors.lastname: McCammon
authors.forename: Michael
authors.initials: M
authors.lastname: Nilges
authors.forename: Martin
authors.initials: M
authors.lastname: Blackledge
mesh_terms: D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D012996:Solutions; D025801:Ubiquitin / Q000737:chemistry*
chemical_list: D012996:Solutions; D025801:Ubiquitin