title: Atomic-accuracy models from 4.5-Å cryo-electron microscopy data with density-guided iterative local refinement.
abstract: We describe a general approach for refining protein structure models on the basis of cryo-electron microscopy maps with near-atomic resolution. The method integrates Monte Carlo sampling with local density-guided optimization, Rosetta all-atom refinement and real-space B-factor fitting. In tests on experimental maps of three different systems with 4.5-Å resolution or better, the method consistently produced models with atomic-level accuracy largely independently of starting-model quality, and it outperformed the molecular dynamics-based MDFF method. Cross-validated model quality statistics correlated with model accuracy over the three test systems.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: DiMaio
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA, USA.|Cyrus Biotechnology, Inc., Seattle, WA, USA.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Keck Advanced Microscopy Laboratory, Department of Biochemistry and Biophysics, University of California, San Francisco, California, USA.
authors.forename: Xueming
authors.initials: X
authors.lastname: Li
authors.affiliation: Center for Structural Systems Biology (CSSB) University Medical Center Eppendorf-Hamburg (UKE), Hamburg, Germany.|Deutsches Elektronen-Synchrotron (DESY), Hamburg, Germany.|Institute of Molecular Biotechnology GmbH (IMBA), Austrian Academy of Sciences, Vienna, Austria.|Research Institute of Molecular Pathology (IMP), Vienna, Austria.
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Brunner
authors.affiliation: Department of Chemistry, Emory University, Atlanta, GA 30322.
authors.forename: Chunfu
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Chemistry, Emory University, Atlanta, GA 30322.
authors.forename: Vincent
authors.initials: V
authors.lastname: Conticello
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Egelman
authors.affiliation: Center for Structural Systems Biology (CSSB) University Medical Center Eppendorf-Hamburg (UKE), Hamburg, Germany.|Deutsches Elektronen-Synchrotron (DESY), Hamburg, Germany.|Institute of Molecular Biotechnology GmbH (IMBA), Austrian Academy of Sciences, Vienna, Austria.|Research Institute of Molecular Pathology (IMP), Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Marlovits
authors.affiliation: Keck Advanced Microscopy Laboratory, Department of Biochemistry and Biophysics, University of California, San Francisco, California, USA.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA, USA.|Howard Hughes Medical Institute, University of Washington, Seattle, Washington, USA.
authors.forename: David
authors.initials: D
authors.lastname: Baker
mesh_terms: D002627:Chemistry, Physical / Q000379:methods*; D020285:Cryoelectron Microscopy; D008958:Models, Molecular; D009010:Monte Carlo Method; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins