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BMC Bioinformatics

Open Access

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

  • Peter Vanhee1, 2Email author,
  • Francois Stricher3,
  • Lies Baeten1, 2,
  • Erik Verschueren3,
  • Luis Serrano3, 4,
  • Frederic Rousseau1, 2 and
  • Joost Schymkowitz1, 2
BMC Bioinformatics201011(Suppl 10):O1

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

Published: 07 December 2010

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

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].

Authors’ Affiliations

(1)
VIB SWITCH laboratory
(2)
Vrije Universiteit Brussel
(3)
EMBL-CRG Systems Biology Unit, CRG-Centre de Regulacio Genomica
(4)
ICREA. Institucio Catala de Recerca i Estudis Avancats. Passeig Lluís Companys

References

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  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

Copyright

© Vanhee et al; licensee BioMed Central Ltd. 2010

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.

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