title: The origin of consistent protein structure refinement from structural averaging.
abstract: Recent studies have shown that explicit solvent molecular dynamics (MD) simulation followed by structural averaging can consistently improve protein structure models. We find that improvement upon averaging is not limited to explicit water MD simulation, as consistent improvements are also observed for more efficient implicit solvent MD or Monte Carlo minimization simulations. To determine the origin of these improvements, we examine the changes in model accuracy brought about by averaging at the individual residue level. We find that the improvement in model quality from averaging results from the superposition of two effects: a dampening of deviations from the correct structure in the least well modeled regions, and a reinforcement of consistent movements towards the correct structure in better modeled regions. These observations are consistent with an energy landscape model in which the magnitude of the energy gradient toward the native structure decreases with increasing distance from the native state.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
authors.forename: Hahnbeom
authors.initials: H
authors.lastname: Park
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: DiMaio
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Box 357370, Seattle, WA 98195, USA. Electronic address: dabaker@u.washington.edu.
authors.forename: David
authors.initials: D
authors.lastname: Baker
mesh_terms: D003627:Data Interpretation, Statistical; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D020836:Protein Structure, Quaternary; D011506:Proteins / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D011506:Proteins; D012997:Solvents; D014867:Water