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Prediction of protein stability changes for single-site mutations using support vector machines

Authors

  • Jianlin Cheng,

    1. Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California, Irvine, California
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  • Arlo Randall,

    1. Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California, Irvine, California
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  • Pierre Baldi

    Corresponding author
    1. Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California, Irvine, California
    2. Department of Biological Chemistry, College of Medicine, University of California, Irvine, California
    • Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California, Irvine, Irvine, CA 92697-3425
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Abstract

Accurate prediction of protein stability changes resulting from single amino acid mutations is important for understanding protein structures and designing new proteins. We use support vector machines to predict protein stability changes for single amino acid mutations leveraging both sequence and structural information. We evaluate our approach using cross-validation methods on a large dataset of single amino acid mutations. When only the sign of the stability changes is considered, the predictive method achieves 84% accuracy—a significant improvement over previously published results. Moreover, the experimental results show that the prediction accuracy obtained using sequence alone is close to the accuracy obtained using tertiary structure information. Because our method can accurately predict protein stability changes using primary sequence information only, it is applicable to many situations where the tertiary structure is unknown, overcoming a major limitation of previous methods which require tertiary information. The web server for predictions of protein stability changes upon mutations (MUpro), software, and datasets are available at http://www.igb.uci.edu/servers/servers.html. Proteins 2006. © 2005 Wiley-Liss, Inc.

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