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Protein loop modeling by using fragment assembly and analytical loop closure

Authors

  • Julian Lee,

    Corresponding author
    1. Department of Bioinformatics and Life Science, Soongsil University, Seoul 156-743, Korea
    2. Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94158
    • Department of Bioinformatics and Life Science, Soongsil University, Seoul 156-743, Korea
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    • Julian Lee and Dongseon Lee contributed equally to this work.

  • Dongseon Lee,

    1. Department of Chemistry, Seoul National University, Seoul 151-747, Korea
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    • Julian Lee and Dongseon Lee contributed equally to this work.

  • Hahnbeom Park,

    1. Department of Chemistry, Seoul National University, Seoul 151-747, Korea
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  • Evangelos A. Coutsias,

    1. Department of Mathematics and Statistics, University of New Mexico, Albuquerque, New Mexico 87131
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  • Chaok Seok

    Corresponding author
    1. Department of Chemistry, Seoul National University, Seoul 151-747, Korea
    • Department of Chemistry, Seoul National University, Seoul 151-747, Korea
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Abstract

Protein loops are often involved in important biological functions such as molecular recognition, signal transduction, or enzymatic action. The three dimensional structures of loops can provide essential information for understanding molecular mechanisms behind protein functions. In this article, we develop a novel method for protein loop modeling, where the loop conformations are generated by fragment assembly and analytical loop closure. The fragment assembly method reduces the conformational space drastically, and the analytical loop closure method finds the geometrically consistent loop conformations efficiently. We also derive an analytic formula for the gradient of any analytical function of dihedral angles in the space of closed loops. The gradient can be used to optimize various restraints derived from experiments or databases, for example restraints for preferential interactions between specific residues or for preferred backbone angles. We demonstrate that the current loop modeling method outperforms previous methods that employ residue-based torsion angle maps or different loop closure strategies when tested on two sets of loop targets of lengths ranging from 4 to 12. Proteins 2010. © 2010 Wiley-Liss, Inc.

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