title: CASP11 refinement experiments with ROSETTA.
abstract: We report new Rosetta-based approaches to tackling the major issues that confound protein structure refinement, and the testing of these approaches in the CASP11 experiment. Automated refinement protocols were developed that integrate a range of sampling methods using parallel computation and multiobjective optimization. In CASP11, we used a more aggressive large-scale structure rebuilding approach for poor starting models, and a less aggressive local rebuilding plus core refinement approach for starting models likely to be closer to the native structure. The more incorrectly modeled a structure was predicted to be, the more it was allowed to vary during refinement. The CASP11 experiment revealed strengths and weaknesses of the approaches: the high-resolution strategy incorporating local rebuilding with core refinement consistently improved starting structures, while the low-resolution strategy incorporating the reconstruction of large parts of the structures improved starting models in some cases but often considerably worsened them, largely because of model selection issues. Overall, the results suggest the high-resolution refinement protocol is a promising method orthogonal to other approaches, while the low-resolution refinement method clearly requires further development. Proteins 2016; 84(Suppl 1):314-322. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, Washington, 98195.|Institute for Protein Design, University of Washington, Seattle, Washington, 98195.
authors.forename: Hahnbeom
authors.initials: H
authors.lastname: Park
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, Washington, 98195.|Institute for Protein Design, University of Washington, Seattle, Washington, 98195.
authors.forename: Frank
authors.initials: F
authors.lastname: DiMaio
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, Washington, 98195. dabaker@uw.edu.|Institute for Protein Design, University of Washington, Seattle, Washington, 98195. dabaker@uw.edu.|Howard Hughes Medical Institute, University of Washington, Seattle, Washington, 98195. dabaker@uw.edu.
authors.forename: David
authors.initials: D
authors.lastname: Baker
mesh_terms: D000465:Algorithms; D020816:Amino Acid Motifs; D019985:Benchmarking; D019295:Computational Biology / Q000379:methods / Q000706:statistics & numerical data*; D006801:Humans; D020407:Internet; D015233:Models, Statistical; D056004:Molecular Dynamics Simulation; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D012984:Software; D013816:Thermodynamics
chemical_list: D011506:Proteins
keywords: Monte Carlo simulation; protein homology modeling; protein loop modeling; structure prediction; structure refinement