Even if we know that two families of homologous proteins interact, we do not necessarily know, which specific proteins interact inside each species. The reason is that most families contain paralogs, i.e., more than one homologous sequence per species. We have developed a tool to predict interacting paralogs between the two protein families, which is based on the idea of inter-protein coevolution: our algorithm matches those members of the two protein families, which belong to the same species and collectively maximize the detectable coevolutionary signal. It is applicable even in cases, where simpler methods based, e.g., on genomic co-localization of genes coding for interacting proteins or orthology-based methods fail. In this method paper, we present an efficient implementation of this idea based on freely available software.
Keywords: Coevolution; Direct coupling analysis; Paralog matching; Predicting interacting paralogs; Protein–protein interaction.