Before revision: High-throughput experiments in bacteria and eukaryotic cells have identified tens of thousands of interactions between proteins. This genome-wide view of the protein interaction universe is coarse-grained, whilst fine-grained detail of macro-molecular interactions critically depends on lower throughput, labor-intensive experiments. Computational approaches using measures of residue co-evolution across proteins show promise, but have been limited to specific interactions. Here we present a new generalized method showing that patterns of evolutionary sequence changes across proteins reflect residues that are close in space , with sufficient accuracy to determine the three-dimensional structure of the protein complexes.
After revision: High-throughput experiments in bacteria and eukaryotic cells have identified tens of thousands of interactions and structural biology has provided detailed functional insight for select 3D protein complexes. An alternative rich source of information about protein interactions is the evolutionary sequence record. Building on earlier work, we show that analysis of correlated evolutionary sequence changes across proteins reflect residues that are close in space , with sufficient accuracy to determine the three-dimensional structure of the protein complexes.