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,…

• NI
  National Institutes of Health

  Award: 1R01GM092802-04
• DT
  Defense Threat Reduction Agency

  Award: N00024-10-D-6318/0024-02