Protein-peptide interactions adopt the same structural motifs as monomeric protein folds

Structure. 2009 Aug 12;17(8):1128-36. doi: 10.1016/j.str.2009.06.013.


We compared the modes of interaction between protein-peptide interfaces and those observed within monomeric proteins and found surprisingly few differences. Over 65% of 731 protein-peptide interfaces could be reconstructed within 1 A RMSD using solely fragment interactions occurring in monomeric proteins. Interestingly, more than 80% of interacting fragments used in reconstructing a protein-peptide binding site were obtained from monomeric proteins of an entirely different structural classification, with an average sequence identity below 15%. Nevertheless, geometric properties perfectly match the interaction patterns observed within monomeric proteins. We show the usefulness of our approach by redesigning the interaction scaffold of nine protein-peptide complexes, for which five of the peptides can be modeled within 1 A RMSD of the original peptide position. These data suggest that the wealth of structural data on monomeric proteins could be harvested to model protein-peptide interactions and, more importantly, that sequence homology is no prerequisite.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Binding Sites
  • Databases, Protein
  • Models, Molecular
  • Peptides / chemistry*
  • Protein Binding
  • Protein Folding*
  • Protein Interaction Mapping / methods*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Proteins / chemistry*
  • Structure-Activity Relationship


  • Peptides
  • Proteins