Robust and accurate prediction of residue-residue interactions across protein interfaces using evolutionary information.
Do the amino acid sequence identities of residues that make contact across protein interfaces covary during evolution? If so, such covariance could be used to predict contacts across interfaces and assemble models of biological complexes. We find that residue pairs identified using a pseudo-likelihood-based method to covary across protein-protein interfaces in the 50S ribosomal unit and 28 additional bacterial protein complexes with known structure are almost always in contact in the complex, provided that the number of aligned sequences is greater than the average length of the two proteins. We use this method to make subunit contact predictions for an additional 36 protein complexes with unknown structures, and present models based on these predictions for the tripartite ATP-independent periplasmic (TRAP) transporter, the tripartite efflux system, the pyruvate formate lyase-activating enzyme complex, and the methionine ABC transporter.DOI: http://dx.doi.org/10.7554/eLife.02030.001.
Department of Biochemistry, Howard Hughes Medical Institute, University of Washington, Seattle, United States Molecular and Cellular Biology Program, University of Washington, Seattle, United States.
Sergey
S
Ovchinnikov
Department of Biochemistry, Howard Hughes Medical Institute, University of Washington, Seattle, United States Facebook Inc., Seattle, United States.
Hetunandan
H
Kamisetty
Department of Biochemistry, Howard Hughes Medical Institute, University of Washington, Seattle, United States dabaker@u.washington.edu.
David
D
Baker
D005075:Biological Evolution; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
D011506:Proteins
protein coevolution; protein complexes; pseudo-likelihood