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

TL;DR

This paper demonstrates that analyzing correlated evolutionary sequence changes can accurately predict 3D contacts and structures of protein complexes, offering a powerful alternative to experimental methods.

Contribution

The study introduces a method leveraging sequence co-evolution to determine protein complex structures and interactions with high accuracy, expanding structural biology tools.

Findings

Successfully predicted 3D contacts in 76 known complexes

Identified interactions in 32 complexes of unknown structure

Distinguished interacting from non-interacting protein pairs

Abstract

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.