title: Advances in Rosetta structure prediction for difficult molecular-replacement problems.
abstract: Recent work has shown the effectiveness of structure-prediction methods in solving difficult molecular-replacement problems. The Rosetta protein structure modeling suite can aid in the solution of difficult molecular-replacement problems using templates from 15 to 25% sequence identity; Rosetta refinement guided by noisy density has consistently led to solved structures where other methods fail. In this paper, an overview of the use of Rosetta for these difficult molecular-replacement problems is provided and new modeling developments that further improve model quality are described. Several variations to the method are introduced that significantly reduce the time needed to generate a model and the sampling required to improve the starting template. The improvements are benchmarked on a set of nine difficult cases and it is shown that this improved method obtains consistently better models in less running time. Finally, strategies for best using Rosetta to solve difficult molecular-replacement problems are presented and future directions for the role of structure-prediction methods in crystallography are discussed.
authors.affiliation: Department of Biochemistry, University of Washington, UW Box 357350, Seattle, WA 98195, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: DiMaio
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D018360:Crystallography, X-Ray / Q000379:methods / Q000639:trends*; D005544:Forecasting / Q000379:methods; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation; D016415:Sequence Alignment; D013698:Templates, Genetic
chemical_list: D010446:Peptide Fragments
keywords: model building; molecular replacement; structure prediction