Three-dimensional modeling of protein interactions and complexes is going ‘omics

High-throughput interaction discovery initiatives have revealed the existence of hundreds of multiprotein complexes whose functions are regulated through thousands of protein–protein interactions (PPIs). However, the structural details of these interactions, often necessary to understand their function, are only available for a tiny fraction, and the experimental difficulties surrounding complex structure determination make computational modeling techniques paramount. In this manuscript, we critically review some of the most recent developments in the field of structural bioinformatics applied to the modeling of protein interactions and complexes, from large macromolecular machines to domain–domain and peptide-mediated interactions. In particular, we place a special emphasis on those methods that can be applied in a proteome-wide manner, and discuss how they will help in the ultimate objective of building 3D interactome networks.