Protein-protein interactions are fundamental to many biological processes.
Experimental screens 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
identifies residues that are close in space with sufficient accuracy to
determine the three-dimensional structure of the protein complexes. We evaluate
prediction performance in blinded tests on 76 complexes of known 3D structure,
predict protein-protein contacts in 32 complexes of unknown structure, and
demonstrate how evolutionary couplings can be used to distinguish between
interacting and non-interacting protein pairs in a large complex. With the
current growth of sequence databases, we expect that the method can be
generalized to genome-wide elucidation of protein-protein interaction networks
and used for interaction predictions at residue resolution.

该研究表明，通过分析蛋白质序列之间的相关进化序列变化，可以准确识别与蛋白质配对的残基，从而确定蛋白质复合物的三维结构，可用于残基分辨率下的互作预测，并且随着序列数据库的增长，这种方法可以扩展到基因组范围内蛋白质相互作用网络的阐明和互作预测。