Protein structure refinement with adaptively restrained homologous replicas

被引:10
作者
Della Corte, Dennis [1 ]
Wildberg, Andre [1 ,3 ]
Schroeder, Gunnar F. [1 ,2 ]
机构
[1] Forschungszentrum Julich, Inst Complex Syst ICS 6, D-52425 Julich, Germany
[2] Univ Dusseldorf, Phys Dept, D-40225 Dusseldorf, Germany
[3] Univ Calif San Diego, Dept Chem & Biochem, 9500 Gilman Dr, La Jolla, CA 92093 USA
关键词
CASP11; structure refinement; homology modeling; molecular dynamics simulation; MOLECULAR-DYNAMICS; STRUCTURE PREDICTION; STATISTICAL POTENTIALS; CATEGORY; SEQUENCE; MODELS; CONFORMATIONS; GENOMICS; DATABASE; CASP;
D O I
10.1002/prot.24939
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A novel protein refinement protocol is presented which utilizes molecular dynamics (MD) simulations of an ensemble of adaptively restrained homologous replicas. This approach adds evolutionary information to the force field and reduces random conformational fluctuations by coupling of several replicas. It is shown that this protocol refines the majority of models from the CASP11 refinement category and that larger conformational changes of the starting structure are possible than with current state of the art methods. The performance of this protocol in the CASP11 experiment is discussed. We found that the quality of the refined model is correlated with the structural variance of the coupled replicas, which therefore provides a good estimator of model quality. Furthermore, some remarkable refinement results are discussed in detail. (C) 2015 Wiley Periodicals, Inc.
引用
收藏
页码:302 / 313
页数:12
相关论文
共 43 条
[1]   Gapped BLAST and PSI-BLAST: a new generation of protein database search programs [J].
Altschul, SF ;
Madden, TL ;
Schaffer, AA ;
Zhang, JH ;
Zhang, Z ;
Miller, W ;
Lipman, DJ .
NUCLEIC ACIDS RESEARCH, 1997, 25 (17) :3389-3402
[2]   PRINCIPLES THAT GOVERN FOLDING OF PROTEIN CHAINS [J].
ANFINSEN, CB .
SCIENCE, 1973, 181 (4096) :223-230
[3]   Protein structure prediction and structural genomics [J].
Baker, D ;
Sali, A .
SCIENCE, 2001, 294 (5540) :93-96
[4]   Optimized Molecular Dynamics Force Fields Applied to the Helix-Coil Transition of Polypeptides [J].
Best, Robert B. ;
Hummer, Gerhard .
JOURNAL OF PHYSICAL CHEMISTRY B, 2009, 113 (26) :9004-9015
[5]  
Branden CI, 1999, METH ENZYMOL
[6]   MolProbity: all-atom structure validation for macromolecular crystallography [J].
Chen, Vincent B. ;
Arendall, W. Bryan, III ;
Headd, Jeffrey J. ;
Keedy, Daniel A. ;
Immormino, Robert M. ;
Kapral, Gary J. ;
Murray, Laura W. ;
Richardson, Jane S. ;
Richardson, David C. .
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2010, 66 :12-21
[7]   Solvent dramatically affects protein structure refinement [J].
Chopra, Gaurav ;
Summa, Christopher M. ;
Levitt, Michael .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (51) :20239-20244
[8]   THE RELATION BETWEEN THE DIVERGENCE OF SEQUENCE AND STRUCTURE IN PROTEINS [J].
CHOTHIA, C ;
LESK, AM .
EMBO JOURNAL, 1986, 5 (04) :823-826
[9]   Understanding protein folding via free-energy surfaces from theory and experiment [J].
Dinner, AR ;
Sali, A ;
Smith, LJ ;
Dobson, CM ;
Karplus, M .
TRENDS IN BIOCHEMICAL SCIENCES, 2000, 25 (07) :331-339
[10]   ACCURATE BOND AND ANGLE PARAMETERS FOR X-RAY PROTEIN-STRUCTURE REFINEMENT [J].
ENGH, RA ;
HUBER, R .
ACTA CRYSTALLOGRAPHICA SECTION A, 1991, 47 :392-400