title: Normal-modes-based prediction of protein conformational changes guided by distance constraints.
abstract: Based on the elastic network model, we develop a novel method that predicts the conformational change of a protein complex given its initial-state crystal structure together with a small set of pairwise distance constraints for the end state. The predicted conformational change, which is a linear combination of multiple low-frequency normal modes that are solved from the elastic network model, is computed as a response displacement induced by a perturbation to the system Hamiltonian that incorporates the given distance constraints. For a list of test cases, we find that the computed response displacement overlaps significantly with the measured conformational changes, when only a handful of pairwise constraints are used (</=10). The performance of this method is also shown to be robust against different choices of pairwise distance constraints and errors in their values. This method, if supplied with the experimentally derived distance constraints (for example, from NMR or other spectroscopic measurements), can be applied to the analysis of protein conformational changes toward transient states.
authors.affiliation: Laboratory of Computational Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. zhengwj@helix.nih.gov
authors.forename: Wenjun
authors.initials: W
authors.lastname: Zheng
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Brooks
mesh_terms: D000465:Algorithms; D000818:Animals; D001703:Biophysics / Q000379:methods*; D019295:Computational Biology; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D009682:Magnetic Resonance Spectroscopy; D015233:Models, Statistical; D008962:Models, Theoretical; D008968:Molecular Conformation; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012984:Software; D013053:Spectrophotometry
references.citation: J Mol Biol. 1997 Jan 17;265(2):217-41
references.pmid: 9020984
references.citation: Phys Rev Lett. 1996 Aug 26;77(9):1905-1908
references.pmid: 10063201
references.citation: J Struct Biol. 2004 Sep;147(3):315-26
references.pmid: 15450300
references.citation: J Mol Biol. 2003 Oct 10;333(1):153-68
references.pmid: 14516750
references.citation: J Mol Biol. 2002 Jul 26;320(5):1011-24
references.pmid: 12126621
references.citation: Biophys J. 2001 Jan;80(1):505-15
references.pmid: 11159421
references.citation: Biophys J. 2004 Jun;86(6):3846-54
references.pmid: 15189881
references.citation: Biophys J. 2002 Feb;82(2):569-81
references.pmid: 11806902
references.citation: J Mol Biol. 2005 Feb 25;346(3):745-59
references.pmid: 15713460
references.citation: Nat Struct Biol. 2000 Sep;7(9):735-9
references.pmid: 10966640
references.citation: Protein Eng. 2001 Jan;14(1):1-6
references.pmid: 11287673
references.citation: Biophys J. 2002 Sep;83(3):1620-30
references.pmid: 12202386
references.citation: Nucleic Acids Res. 1998 Sep 15;26(18):4280-90
references.pmid: 9722650
references.citation: Biophys J. 2002 Aug;83(2):663-80
references.pmid: 12124255
references.citation: Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13253-8
references.pmid: 14585932