Blind predictions of protein interfaces by docking calculations in CAPRI

Authors

  • Marc F. Lensink,

    1. Genome and Network Bioinformatics, CP 263, BC6, Université Libre de Bruxelles, 1050 Brussels, Belgium
    2. Structure and Function of Biological Membranes, Université Libre de Bruxelles, Brussels, Belgium
    Search for more papers by this author
  • Shoshana J. Wodak

    Corresponding author
    1. Molecular Structure and Function Program, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
    2. Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    3. Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    • Molecular Structure and Function Program, Hospital for Sick Children, 555 University Av., Toronto, ON M5G 1X8, Canada
    Search for more papers by this author

  • The authors state no conflict of interest.

Abstract

Reliable prediction of the amino acid residues involved in protein–protein interfaces can provide valuable insight into protein function, and inform mutagenesis studies, and drug design applications. A fast-growing number of methods are being proposed for predicting protein interfaces, using structural information, energetic criteria, or sequence conservation or by integrating multiple criteria and approaches. Overall however, their performance remains limited, especially when applied to nonobligate protein complexes, where the individual components are also stable on their own. Here, we evaluate interface predictions derived from protein–protein docking calculations. To this end we measure the overlap between the interfaces in models of protein complexes submitted by 76 participants in CAPRI (Critical Assessment of Predicted Interactions) and those of 46 observed interfaces in 20 CAPRI targets corresponding to nonobligate complexes. Our evaluation considers multiple models for each target interface, submitted by different participants, using a variety of docking methods. Although this results in a substantial variability in the prediction performance across participants and targets, clear trends emerge. Docking methods that perform best in our evaluation predict interfaces with average recall and precision levels of about 60%, for a small majority (60%) of the analyzed interfaces. These levels are significantly higher than those obtained for nonobligate complexes by most extant interface prediction methods. We find furthermore that a sizable fraction (24%) of the interfaces in models ranked as incorrect in the CAPRI assessment are actually correctly predicted (recall and precision ≥50%), and that these models contribute to 70% of the correct docking-based interface predictions overall. Our analysis proves that docking methods are much more successful in identifying interfaces than in predicting complexes, and suggests that these methods have an excellent potential of addressing the interface prediction challenge. Proteins 2010. © 2010 Wiley-Liss, Inc.

Ancillary