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  • Oral presentation
  • Open Access

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

  • 1, 2Email author,
  • 3,
  • 1, 2,
  • 3,
  • 3, 4,
  • 1, 2 and
  • 1, 2
BMC Bioinformatics201011 (Suppl 10) :O1

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

  • Published:

Keywords

  • Peptide
  • Sequence Homology
  • Geometric Property
  • Combinatorial Library
  • Interaction Pattern

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].

Authors’ Affiliations

(1)
VIB SWITCH laboratory, Pleinlaan 2, 1050 Brussels, Belgium
(2)
Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium
(3)
EMBL-CRG Systems Biology Unit, CRG-Centre de Regulacio Genomica, Dr. Aiguader 88, 08003 Barcelona, Spain
(4)
ICREA. Institucio Catala de Recerca i Estudis Avancats. Passeig Lluís Companys, 23 08010 Barcelona, Spain

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

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