PEP-SiteFinder: a tool for the blind identification of peptide binding sites on protein surfaces

Abstract

Peptide-protein interactions are important to many processes of life, particularly for signal transmission or regulatory mechanisms. When no information is known about the interaction between a protein and a peptide, it is of interest to propose candidate sites of interaction at the protein surface, to assist the design of biological experiments to probe the interaction, or to serve as a starting point for more focused in silico approaches. PEP-SiteFinder is a tool that will, given the structure of a protein and the sequence of a peptide, identify protein residues predicted to be at peptide-protein interface. PEP-SiteFinder relies on the 3D de novo generation of peptide conformations given its sequence. These conformations then undergo a fast blind rigid docking on the complete protein surface, and we have found, as the result of a benchmark over 41 complexes, that the best poses overlap to some extent the experimental patch of interaction for close to 90% complexes. In addition, PEP-SiteFinder also returns a propensity index we have found informative about the confidence of the prediction. The PEP-SiteFinder web server is available at http://bioserv.rpbs.univ-paris-diderot.fr/PEP-SiteFinder.

Figure 1.

PEP-SiteFinder flowchart.

Figure 2.

PEP-SiteFinder interactive page for the exploration of the best poses for the PriA helicase—SSB peptide complex (PDB code: 4NL8). Protein residues are colored according to their predicted propensities, from blue (0) to red (100).

Figure 3.

PEP-SiteFinder (A) and PepSite (B) performance over the PeptiDB core subset. Fraction of residues of the binding site contacted by the 10 best poses. (C) Probability that a residue is in the binding site (correct prediction) as a function of the propensity. The error bars correspond to the standard deviation estimated over five independent runs.