A multi-scale coevolutionary approach to predict interactions between protein domains

by Giancarlo Croce, Thomas Gueudr é, Maria Virginia Ruiz Cuevas, Victoria Keidel, Matteo Figliuzzi, Hendrik Szurmant, Martin Weigt Interacting proteins and protein domains coevolve on multiple scales, from their correlated presence across species, to correlations in amino-acid usage. Genomic databases provide rapidly growing data for variability in genomic protein content and in protein sequences, calling for computational pr edictions of unknown interactions. We first introduce the concept ofdirect phyletic couplings, based on global statistical models of phylogenetic profiles. They strongly increase the accuracy of predicting pairs of related protein domains beyond simpler correlation-based approaches like phylogenetic profiling (80% vs. 30 –50% positives out of the 1000 highest-scoring pairs). Combined with the direct coupling analysis of inter-protein residue-residue coevolution, we provide multi-scale evidence for direct but unknown interaction between protein families. An in-depth discussion shows these to be biologically sensibl e and directly experimentally testable. Negative phyletic couplings highlight alternative solutions for the same functionality, including documented cases of convergent evolution. Thereby our work proves the strong potential of global statistical modeling approaches to genome-wide coevolutionary ana lysis, far beyond the established use for individual protein complexes and domain-domain interactions.
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research