Skip to main content
  • Oral presentation
  • Open access
  • Published:

Modeling protein-peptide interactions using protein fragments: fitting the pieces?

An estimated 15-40% of all interactions in the cell are mediated through protein-peptide interactions [1, 2] meaning that, at the most extreme, nearly every protein is affected either directly or indirectly by peptide-binding events.

We compared the modes of interaction between protein-peptide interfaces and those observed within monomeric proteins and found surprisingly little differences [3]. Over 65% of 731 protein-peptide interfaces could be reconstructed within 1 Å RMSD using solely fragment interactions occurring in monomeric proteins, using our fragment database BriX containing over 1000 non-redundant protein structures [4]. 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 (see Figure 1), suggesting that our fragment interaction approach might provide an alternative to homology modelling.

Figure 1
figure 1

Relation between intermolecular protein-peptide interface architectures (blue for receptor, green for peptide ligand) and intramolecular protein architectures from our database of monomeric proteins, BriX (red) [4].

We show the usefulness of our method by redesigning the interaction scaffold of nine protein-peptide complexes, for which five of the peptides can be modelled to within 1 Å 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. In addition, we have made our dataset of 505 non-redundant protein-peptide complexes from 1431 entries in the PDB available at http://pepx.switchlab.org[5] and the BriX database at http://brix.crg.es[6].

References

  1. Neduva V, Linding R, Su-Angrand I, Stark A, de Masi F, Gibson TJ, Lewis J, Serrano L, Russell RB: Systematic discovery of new recognition peptides mediating protein interaction networks. PLoS Biol 2005, 3(12):e405. 10.1371/journal.pbio.0030405

    Article  PubMed Central  PubMed  Google Scholar 

  2. Petsalaki E, Russell RB: Peptide-mediated interactions in biological systems: new discoveries and applications. Curr Opin Biotechnol 2008, 19(4):344–350. 10.1016/j.copbio.2008.06.004

    Article  CAS  PubMed  Google Scholar 

  3. Vanhee P, Stricher F, Baeten L, Verschueren E, Lenaerts T, Serrano L, Rousseau F, Schymkowitz J: Protein-Peptide Interactions Adopt the Same Structural Motifs as Monomeric Protein Folds. Structure 2009, 17(8):1128–1136. 10.1016/j.str.2009.06.013

    Article  CAS  PubMed  Google Scholar 

  4. Baeten L, Reumers J, Tur V, Stricher F, Lenaerts T, Serrano L, Rousseau F, Schymkowitz J: Reconstruction of protein backbones from the BriX collection of canonical protein fragments. PLoS Comput Biol 2008, 4(5):e1000083. 10.1371/journal.pcbi.1000083

    Article  PubMed Central  PubMed  Google Scholar 

  5. Vanhee P, Reumers J, Stricher F, Baeten L, Serrano L, Schymkowitz J, Rousseau F: PepX: a structural database of non-redundant protein-peptide complexes. Nucleic Acids Research 2010, 38(Database issue):D545–551. 10.1093/nar/gkp893

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Vanhee P, Verschueren E, Stricher F, Baeten L, Serrano L, Schymkowitz J, Rousseau F: BriX: a database of protein building blocks for structural analysis, modeling and design. Nucleic Acids Research. Nucleic Acids Research 2010.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter Vanhee.

Rights and permissions

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and permissions

About this article

Cite this article

Vanhee, P., Stricher, F., Baeten, L. et al. Modeling protein-peptide interactions using protein fragments: fitting the pieces?. BMC Bioinformatics 11 (Suppl 10), O1 (2010). https://doi.org/10.1186/1471-2105-11-S10-O1

Download citation

  • Published:

  • DOI: https://doi.org/10.1186/1471-2105-11-S10-O1

Keywords