title: Achieving reliability and high accuracy in automated protein docking: ClusPro, PIPER, SDU, and stability analysis in CAPRI rounds 13-19.
abstract: Our approach to protein-protein docking includes three main steps. First, we run PIPER, a rigid body docking program based on the Fast Fourier Transform (FFT) correlation approach, extended to use pairwise interactions potentials. Second, the 1000 best energy conformations are clustered, and the 30 largest clusters are retained for refinement. Third, the stability of the clusters is analyzed by short Monte Carlo simulations, and the structures are refined by the medium-range optimization method SDU. The first two steps of this approach are implemented in the ClusPro 2.0 protein-protein docking server. Despite being fully automated, the last step is computationally too expensive to be included in the server. When comparing the models obtained in CAPRI rounds 13-19 by ClusPro, by the refinement of the ClusPro predictions and by all predictor groups, we arrived at three conclusions. First, for the first time in the CAPRI history, our automated ClusPro server was able to compete with the best human predictor groups. Second, selecting the top ranked models, our current protocol reliably generates high-quality structures of protein-protein complexes from the structures of separately crystallized proteins, even in the absence of biological information, provided that there is limited backbone conformational change. Third, despite occasional successes, homology modeling requires further improvement to achieve reliable docking results.
authors.affiliation: BioMolecular Engineering Research Center, Boston University, Boston, Massachusetts 02215, USA. vajda@bu.edu
authors.forename: Dima
authors.initials: D
authors.lastname: Kozakov
authors.forename: David R
authors.initials: DR
authors.lastname: Hall
authors.forename: Dmitri
authors.initials: D
authors.lastname: Beglov
authors.forename: Ryan
authors.initials: R
authors.lastname: Brenke
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Comeau
authors.forename: Yang
authors.initials: Y
authors.lastname: Shen
authors.forename: Keyong
authors.initials: K
authors.lastname: Li
authors.forename: Jiefu
authors.initials: J
authors.lastname: Zheng
authors.forename: Pirooz
authors.initials: P
authors.lastname: Vakili
authors.forename: Ioannis Ch
authors.initials: ICh
authors.lastname: Paschalidis
authors.forename: Sandor
authors.initials: S
authors.lastname: Vajda
mesh_terms: D000465:Algorithms; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D012984:Software
chemical_list: D011506:Proteins
references.citation: Proteins. 1999 May 15;35(3):364-73
references.pmid: 10328272
references.citation: Proteins. 2010 Jul;78(9):2131-43
references.pmid: 20455268
references.citation: BMC Bioinformatics. 2008 Jan 23;9:40
references.pmid: 18215316
references.citation: Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10080-5
references.pmid: 20479265
references.citation: Proteins. 2006 Nov 1;65(2):392-406
references.pmid: 16933295
references.citation: Proteins. 2000 Aug 15;40(3):525-37
references.pmid: 10861944
references.citation: Biophys J. 2003 Mar;84(3):1895-901
references.pmid: 12609891
references.citation: Bioinformatics. 2004 Jan 1;20(1):45-50
references.pmid: 14693807
references.citation: Proteins. 2003 Nov 15;53(3):693-707
references.pmid: 14579360
references.citation: Curr Protoc Bioinformatics. 2006 Oct;Chapter 5:Unit-5.6
references.pmid: 18428767
references.citation: Proteins. 2004 Jul 1;56(1):93-101
references.pmid: 15162489
references.citation: Proteins. 2003 Dec 1;53(4):840-54
references.pmid: 14635126
references.citation: Biophys J. 2005 Aug;89(2):867-75
references.pmid: 15908573
references.citation: PLoS Comput Biol. 2008 Oct;4(10):e1000191
references.pmid: 18846200
references.citation: Proteins. 2008 Aug 15;72(3):993-1004
references.pmid: 18300245
references.citation: Biophys J. 2008 Nov 1;95(9):4217-27
references.pmid: 18676649