Correlations from structure and phylogeny combine constructively in the inference of protein partners from sequences.

Inferring protein-protein interactions from sequences is an important task in computational biology. Recent methods based on Direct Coupling Analysis (DCA) or Mutual Information (MI) allow to find interaction partners among paralogs of two protein families. Does successful inference mainly rely on correlations from structural contacts or from phylogeny, or both? Do these two types of signal combine constructively or hinder each other? To address these questions, we generate and analyze synthetic data produced using a minimal model that allows us to control the amounts of structural constraints and phylogeny.