Identification of direct residue contacts in protein–protein interaction by message passing

Understanding the molecular determinants of specificity in protein-protein interaction is an outstanding challenge of postgenome biology. The availability of large protein databases generated from sequences of hundreds of bacterial genomes enables various statistical approaches to this problem. In this context covariance-based methods have been used to identify correlation between amino acid positions in interacting proteins. However, these methods have an important shortcoming, in that they cannot distinguish between directly and indirectly correlated residues. We developed a method that combines covariance analysis with global inference analysis, adopted from use in statistical physics. Applied to a set of…

• NS
  National Science Foundation

  Awards: PHY-0822283, 0532925, 0822283
• NI
  National Institutes of Health

  Award: GM019416
• CF
  Center for Theoretical Biological Physics

  Award: PHY-0822283