RT Journal Article
SR Electronic
T1 Sequence co-evolution gives 3D contacts and structures of protein complexes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 004762
DO 10.1101/004762
A1 Thomas A. Hopf
A1 Charlotta P. I. Schärfe
A1 João P. G. L. M. Rodrigues
A1 Anna G. Green
A1 Chris Sander
A1 Alexandre M. J. J. Bonvin
A1 Debora S. Marks
YR 2014
UL http://biorxiv.org/content/early/2014/09/15/004762.abstract
AB 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.