Taking geometry to its edge: Fast unbound rigid (and hinge-bent) docking

Authors

  • Dina Schneidman-Duhovny,

    1. School of Computer Science, Beverly and Raymond Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel
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    • Dina Schneidman-Duhovny and Yuval Inbar contributed equally to the work

  • Yuval Inbar,

    1. School of Computer Science, Beverly and Raymond Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel
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    • Dina Schneidman-Duhovny and Yuval Inbar contributed equally to the work

  • Vladimir Polak,

    1. School of Computer Science, Beverly and Raymond Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel
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  • Maxim Shatsky,

    1. School of Computer Science, Beverly and Raymond Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel
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  • Inbal Halperin,

    1. Department of Human Genetics and Molecular Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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  • Hadar Benyamini,

    1. Department of Human Genetics and Molecular Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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  • Adi Barzilai,

    1. Department of Human Genetics and Molecular Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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  • Oranit Dror,

    1. School of Computer Science, Beverly and Raymond Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel
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  • Nurit Haspel,

    1. School of Computer Science, Beverly and Raymond Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel
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  • Ruth Nussinov,

    1. Basic Research Program, SAIC-Frederick, Inc., Laboratory of Experimental and Computational Biology, NCI-Frederick, Frederick, Maryland
    2. Department of Human Genetics and Molecular Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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  • Haim J. Wolfson

    Corresponding author
    1. School of Computer Science, Beverly and Raymond Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel
    • School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel
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  • This article is a US Government work and, as such, is in the public domain in the United States of America.

Abstract

We present a very efficient rigid “unbound” soft docking methodology, which is based on detection of geometric shape complementarity, allowing liberal steric clash at the interface. The method is based on local shape feature matching, avoiding the exhaustive search of the 6D transformation space. Our experiments at CAPRI rounds 1 and 2 show that although the method does not perform an exhaustive search of the 6D transformation space, the “correct” solution is never lost. However, such a solution might rank low for large proteins, because there are alternatives with significantly larger geometrically compatible interfaces. In many cases this problem can be resolved by successful a priori focusing on the vicinity of potential binding sites as well as the extension of the technique to flexible (hinge-bent) docking. This is demonstrated in the experiments performed as a lesson from our CAPRI experience. Proteins 2003;52:107–112. Published 2003 Wiley-Liss, Inc.

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