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Prediction of protein–protein binding free energies

Authors

  • Thom Vreven,

    1. Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605
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  • Howook Hwang,

    1. Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605
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  • Brian G. Pierce,

    1. Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605
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  • Zhiping Weng

    Corresponding author
    1. Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605
    • Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Room 1010, Lazare Research Building, 364 Plantation St., Worcester, MA 01605
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Abstract

We present an energy function for predicting binding free energies of protein–protein complexes, using the three-dimensional structures of the complex and unbound proteins as input. Our function is a linear combination of nine terms and achieves a correlation coefficient of 0.63 with experimental measurements when tested on a benchmark of 144 complexes using leave-one-out cross validation. Although we systematically tested both atomic and residue-based scoring functions, the selected function is dominated by residue-based terms. Our function is stable for subsets of the benchmark stratified by experimental pH and extent of conformational change upon complex formation, with correlation coefficients ranging from 0.61 to 0.66.

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