title: Targeted conformational search with map-restrained self-guided Langevin dynamics: application to flexible fitting into electron microscopic density maps.
abstract: We present a map-restrained self-guided Langevin dynamics (MapSGLD) simulation method for efficient targeted conformational search. The targeted conformational search represents simulations under restraints defined by experimental observations and/or by user specified structural requirements. Through map-restraints, this method provides an efficient way to maintain substructures and to set structure targets during conformational searching. With an enhanced conformational searching ability of self-guided Langevin dynamics, this approach is suitable for simulating large-scale conformational changes, such as the formation of macromolecular assemblies and transitions between different conformational states. Using several examples, we illustrate the application of this method in flexible fitting of atomic structures into density maps derived from cryo-electron microscopy.
authors.affiliation: Laboratory of Computational Biology, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA. Electronic address: wuxw@nhlbi.nih.gov.
authors.forename: Xiongwu
authors.initials: X
authors.lastname: Wu
authors.affiliation: Laboratory of Cell Biology, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
authors.forename: Sriram
authors.initials: S
authors.lastname: Subramaniam
authors.affiliation: BioMaPS Institute and Dept. of Chemistry & Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Case
authors.affiliation: Thomas Jefferson High School for Science and Technology, Alexandria, VA 22312, USA.
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Wu
authors.affiliation: Laboratory of Computational Biology, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Brooks
mesh_terms: D000465:Algorithms; D001426:Bacterial Proteins / Q000737:chemistry / Q000648:ultrastructure; D018834:Chaperonin 60 / Q000737:chemistry / Q000648:ultrastructure; D003198:Computer Simulation; D020285:Cryoelectron Microscopy / Q000379:methods; D003627:Data Interpretation, Statistical; D056385:Group II Chaperonins / Q000737:chemistry / Q000648:ultrastructure; D008958:Models, Molecular; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D018834:Chaperonin 60; C034284:IgG Fc-binding protein, Streptococcus; D056385:Group II Chaperonins
keywords: Electron microscopy; Flexible fitting; Map-restraint; Self-guided Langevin dynamics; Targeted conformational search