Get access

Exploiting sequence and structure homologs to identify protein–protein binding sites

Authors

  • Jo-Lan Chung,

    1. Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California
    2. San Diego Supercomputer Center, University of California, San Diego, La Jolla, California
    Search for more papers by this author
  • Wei Wang,

    1. Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California
    Search for more papers by this author
  • Philip E. Bourne

    Corresponding author
    1. Department of Pharmacology, University of California, San Diego, La Jolla, California
    2. San Diego Supercomputer Center, University of California, San Diego, La Jolla, California
    • Department of Pharmacology, San Diego Supercomputer Center, University of California, San Diego, Gilman Drive, La Jolla, CA 92093-0537
    Search for more papers by this author

Abstract

A rapid increase in the number of experimentally derived three-dimensional structures provides an opportunity to better understand and subsequently predict protein–protein interactions. In this study, structurally conserved residues were derived from multiple structure alignments of the individual components of known complexes and the assigned conservation score was weighted based on the crystallographic B factor to account for the structural flexibility that will result in a poor alignment. Sequence profile and accessible surface area information was then combined with the conservation score to predict protein–protein binding sites using a Support Vector Machine (SVM). The incorporation of the conservation score significantly improved the performance of the SVM. About 52% of the binding sites were precisely predicted (greater than 70% of the residues in the site were identified); 77% of the binding sites were correctly predicted (greater than 50% of the residues in the site were identified), and 21% of the binding sites were partially covered by the predicted residues (some residues were identified). The results support the hypothesis that in many cases protein interfaces require some residues to provide rigidity to minimize the entropic cost upon complex formation. Proteins 2006. © 2005 Wiley-Liss, Inc.

Ancillary