PepSite

A structural method to predict peptide/protein binding
Evangelia Petsalaki, Alexander Stark, Eduardo Garcia Urdiales, Rob Russell

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About PepSite

Protein-protein interactions are vital for all cellular mechanisms. A major class of such interactions are those where a globular domain in one protein binds to a short peptide stretch in another. Phosphorylation/ dephosphorylation events, other post-translational modifications, and dozens of signalling, targetting & trafficking procedures are known to occur by way of this kind of interaction. Often proteins sharing an interaction partner contain a common peptide pattern or linear motif known to mediate the interaction. For example, SH3 domains bind to a PxxP pattern, WW domains to PPxY, 14-3-3 domains to RxSxP, etc. The availability of hundreds of new peptides known or predicted to interact with a particular protein, in addition to the fact that structural genomics initiatives, and the general increased pace of structure determination, have provided representative structures for many if not most globular domains suggests the need for methods that specifically fit a peptide onto the surface of a 3D structure.

PepSite is just such an approach. We have constructed spatial position-specific scoring matrices (PSSMs) capturing the preferred environment for each amino acid when bound as a peptide from a database of protein/peptide structure. These matrices are then used to score the surface of target proteins in order to find candidate binding sites of each residue of a particular peptide, which are then combined to suggest the potential binding site and rough orientation of this peptide. The method performs well in a benchmark, and we have shown that it is capable of identifying the true binding site of peptides and roughly orienting them on protein surfaces.

When using PepSite please cite: Petsalaki E, Stark A, GarcĂ­a-Urdiales E, Russell RB, Accurate prediction of peptide binding sites on protein surfaces, PLoS Comput Biol., 2009 Mar;5(3):e1000335.