Data from: Sequence co-evolution gives 3D contacts and structures of protein complexes

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 sequences, 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.

蛋白质-蛋白质相互作用（Protein-protein interactions）是诸多生物过程的核心基础。实验筛选已鉴定出数万种此类相互作用，结构生物学亦为部分已表征的三维蛋白质复合物提供了详尽的功能解析。关于蛋白质相互作用的另一重要信息来源，便是进化序列记录。基于此前的研究基础，我们证实，对跨蛋白质的协同进化序列变化开展分析，可精准识别空间上邻近的氨基酸残基，其精度足以解析蛋白质复合物的三维结构。我们针对76个已知三维结构的复合物开展盲法测试以评估预测性能，同时对32个未知结构的复合物预测其蛋白质-蛋白质接触位点，并展示了如何利用进化耦合（evolutionary couplings）在大型复合物中区分相互作用与非相互作用的蛋白质对。随着当前序列数据的快速增长，我们预期该方法可推广至全基因组范围内的蛋白质-蛋白质相互作用网络解析，并可用于氨基酸残基分辨率级别的相互作用预测。