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Achieving reliability and high accuracy in automated protein docking: Cluspro, PIPER, SDU, and stability analysis in CAPRI rounds 13–19

Authors

  • Dima Kozakov,

    Corresponding author
    1. BioMolecular Engineering Research Center, Boston University, Boston, Massachusetts
    2. Department of Biomedical Engineering, Boston University, Boston, Massachusetts
    • Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215
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    • Dima Kozakov, David R. Hall, Dmitri Beglov, and Ryan Brenke are the joint first authors to this work.

  • David R. Hall,

    1. BioMolecular Engineering Research Center, Boston University, Boston, Massachusetts
    2. Department of Biomedical Engineering, Boston University, Boston, Massachusetts
    Search for more papers by this author
    • Dima Kozakov, David R. Hall, Dmitri Beglov, and Ryan Brenke are the joint first authors to this work.

  • Dmitri Beglov,

    1. BioMolecular Engineering Research Center, Boston University, Boston, Massachusetts
    2. Department of Biomedical Engineering, Boston University, Boston, Massachusetts
    Search for more papers by this author
    • Dima Kozakov, David R. Hall, Dmitri Beglov, and Ryan Brenke are the joint first authors to this work.

  • Ryan Brenke,

    1. BioMolecular Engineering Research Center, Boston University, Boston, Massachusetts
    2. Department of Biomedical Engineering, Boston University, Boston, Massachusetts
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    • Dima Kozakov, David R. Hall, Dmitri Beglov, and Ryan Brenke are the joint first authors to this work.

  • Stephen R. Comeau,

    1. Dyax Corporation, Cambridge, Massachusetts
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  • Yang Shen,

    1. BioMolecular Engineering Research Center, Boston University, Boston, Massachusetts
    2. Program in Systems Engineering, Boston University, Boston, Massachusetts
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  • Keyong Li,

    1. Program in Systems Engineering, Boston University, Boston, Massachusetts
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  • Jiefu Zheng,

    1. Program in Systems Engineering, Boston University, Boston, Massachusetts
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  • Pirooz Vakili,

    1. Program in Systems Engineering, Boston University, Boston, Massachusetts
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  • Ioannis Ch. Paschalidis,

    1. Program in Systems Engineering, Boston University, Boston, Massachusetts
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  • Sandor Vajda

    Corresponding author
    1. BioMolecular Engineering Research Center, Boston University, Boston, Massachusetts
    2. Department of Biomedical Engineering, Boston University, Boston, Massachusetts
    • Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215, USA
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  • The authors state no conflict of interest.

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. Proteins 2010. © 2010 Wiley-Liss, Inc.

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