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Toward an atomistic model for predicting transcription-factor binding sites

Authors

  • Robert G. Endres,

    Corresponding author
    1. Center for Computational Sciences and Computer Science & Mathematics Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee
    • Computer Science & Mathematics Division, Oak Ridge National Laboratory, P.O. Box 2008, Oak Ridge, TN 37831-6164
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  • Thomas C. Schulthess,

    1. Center for Computational Sciences and Computer Science & Mathematics Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee
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  • Ned S. Wingreen

    1. NEC Laboratories America, Inc., Princeton, New Jersey
    Current affiliation:
    1. Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014
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Abstract

Identifying the specific DNA-binding sites of transcription-factor proteins is essential to understanding the regulation of gene expression in the cell. Bioinformatics approaches are fast compared to experiments, but require prior knowledge of multiple binding sites for each protein. Here, we present an atomistic force-field method to predict binding sites based only on the X-ray structure of a related bound complex. Specific flexible contacts between the protein and DNA are modeled by a library of amino acid side-chain rotamers. Using the example of the mouse transcription factor, Zif268, a well-studied zinc-finger protein, we show that the protein sequence alone, without the detailed experimental structure, gives a strong bias toward the consensus binding site. Proteins 2004. © 2004 Wiley-Liss, Inc.

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