Prediction of protein-protein interactions using distant conservation of sequence patterns and structure relationships

Jordi Espadaler, Oriol Romero-Isart, Richard M. Jackson, Baldo Oliva

    Research output: Contribution to journalArticleResearchpeer-review

    85 Citations (Scopus)


    Motivation: Given that association and dissociation of protein molecules is crucial in most biological processes several in silico methods have been recently developed to predict protein-protein interactions. Structural evidence has shown that usually interacting pairs of close homologs (interologs) physically interact in the same way. Moreover, conservation of an interaction depends on the conservation of the interface between interacting partners. In this article we make use of both, structural similarities among domains of known interacting proteins found in the Database of Interacting Proteins (DIP) and conservation of pairs of sequence patches involved in protein-protein interfaces to predict putative protein interaction pairs. Results: We have obtained a large amount of putative protein-protein interaction (∼130 000). The list is independent from other techniques both experimental and theoretical. We separated the list of predictions into three sets according to their relationship with known interacting proteins found in DIP. For each set, only a small fraction of the predicted protein pairs could be independently validated by cross checking with the Human Protein Reference Database (HPRD). The fraction of validated protein pairs was always larger than that expected by using random protein pairs. Furthermore, a correlation map of interacting protein pairs was calculated with respect to molecular function, as defined in the Gene Ontology database. It shows good consistency of the predicted interactions with data in the HPRD database. The intersection between the lists of interactions of other methods and ours produces a network of potentially high-confidence interactions. © The Author 2005. Published by Oxford University Press. All rights reserved.
    Original languageEnglish
    Pages (from-to)3360-3368
    Publication statusPublished - 15 Aug 2005


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