Interolog interfaces in protein-protein docking

James D. Alsop, Julie C. Mitchell

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Proteins are essential elements of biological systems, and their function typically relies on their ability to successfully bind to specific partners. Recently, an emphasis of study into protein interactions has been on hot spots, or residues in the binding interface that make a significant contribution to the binding energetics. In this study, we investigate how conservation of hot spots can be used to guide docking prediction. We show that the use of evolutionary data combined with hot spot prediction highlights near-native structures across a range of benchmark examples. Our approach explores various strategies for using hot spots and evolutionary data to score protein complexes, using both absolute and chemical definitions of conservation along with refinements to these strategies that look at windowed conservation and filtering to ensure a minimum number of hot spots in each binding partner. Finally, structure-based models of orthologs were generated for comparison with sequence-based scoring. Using two data sets of 22 and 85 examples, a high rate of top 10 and top 1 predictions are observed, with up to 82% of examples returning a top 10 hit and 35% returning top 1 hit depending on the data set and strategy applied; upon inclusion of the native structure among the decoys, up to 55% of examples yielded a top 1 hit. The 20 common examples between data sets show that more carefully curated interolog data yields better predictions, particularly in achieving top 1 hits.

Original languageEnglish
Pages (from-to)1940-1946
Number of pages7
JournalProteins: Structure, Function and Genetics
Volume83
Issue number11
DOIs
StatePublished - Nov 2015
Externally publishedYes

Funding

FundersFunder number
National Science Foundation
Directorate for Mathematical and Physical Sciences1160360

    Keywords

    • Hot spot
    • Interolog
    • Molecular evolution
    • Mutagenesis
    • Ortholog
    • Protein-protein docking

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