Inter-residue, inter-protein and inter-family coevolution: bridging the scales

•Coevolutionary modeling has an immense potential in structural systems biology.•Interaction between two protein families can be detected.•Specific interaction partners inside families can be deduced.•Contact residues between interacting proteins can be predicted.•Predicted inter-protein contacts can guide in silico protein-complex assembly. Interacting proteins coevolve at multiple but interconnected scales, from the residue–residue over the protein–protein up to the family–family level. The recent accumulation of enormous amounts of sequence data allows for the development of novel, data-driven computational approaches. Notably, these approaches can bridge scales within a single statistical framework. Although being currently applied mostly to isolated problems on single scales, their immense potential for an evolutionary informed, structural systems biology is steadily emerging.