Get access

Predicting permanent and transient protein–protein interfaces

Authors

  • David La,

    1. Department of Biological Sciences, College of Science, Purdue University, West Lafayette, Indiana 47907
    2. Markey Center for Structural Biology, Purdue University, West Lafayette, Indiana 47907
    Search for more papers by this author
  • Misun Kong,

    1. Department of Biological Sciences, College of Science, Purdue University, West Lafayette, Indiana 47907
    Search for more papers by this author
  • William Hoffman,

    1. Department of Biological Sciences, College of Science, Purdue University, West Lafayette, Indiana 47907
    Search for more papers by this author
  • Youn Im Choi,

    1. Department of Biological Sciences, College of Science, Purdue University, West Lafayette, Indiana 47907
    2. Markey Center for Structural Biology, Purdue University, West Lafayette, Indiana 47907
    Search for more papers by this author
  • Daisuke Kihara

    Corresponding author
    1. Department of Biological Sciences, College of Science, Purdue University, West Lafayette, Indiana 47907
    2. Markey Center for Structural Biology, Purdue University, West Lafayette, Indiana 47907
    3. Department of Computer Science, College of Science, Purdue University, West Lafayette, Indiana 47907
    • Department of Biological Sciences, College of Science, Purdue University, West Lafayette, IN 47907
    Search for more papers by this author

Abstract

Protein–protein interactions (PPIs) are involved in diverse functions in a cell. To optimize functional roles of interactions, proteins interact with a spectrum of binding affinities. Interactions are conventionally classified into permanent and transient, where the former denotes tight binding between proteins that result in strong complexes, whereas the latter compose of relatively weak interactions that can dissociate after binding to regulate functional activity at specific time point. Knowing the type of interactions has significant implications for understanding the nature and function of PPIs. In this study, we constructed amino acid substitution models that capture mutation patterns at permanent and transient type of protein interfaces, which were found to be different with statistical significance. Using the substitution models, we developed a novel computational method that predicts permanent and transient protein binding interfaces (PBIs) in protein surfaces. Without knowledge of the interacting partner, the method uses a single query protein structure and a multiple sequence alignment of the sequence family. Using a large dataset of permanent and transient proteins, we show that our method, BindML+, performs very well in protein interface classification. A very high area under the curve (AUC) value of 0.957 was observed when predicted protein binding sites were classified. Remarkably, near prefect accuracy was achieved with an AUC of 0.991 when actual binding sites were classified. The developed method will be also useful for protein design of permanent and transient PBIs. © Proteins 2013. © 2012 Wiley Periodicals, Inc.

Get access to the full text of this article

Ancillary