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. 2019 Jul 2;47(W1):W365-W372.
doi: 10.1093/nar/gkz478.

PatchSearch: a web server for off-target protein identification

Julien Rey  1   2 , Inès Rasolohery  1 , Pierre Tufféry  1   2 , Frédéric Guyon  1 , Gautier Moroy  1
Affiliations

PatchSearch: a web server for off-target protein identification

Julien Rey et al. Nucleic Acids Res. .

Abstract

The large number of proteins found in the human body implies that a drug may interact with many proteins, called off-target proteins, besides its intended target. The PatchSearch web server provides an automated workflow that allows users to identify structurally conserved binding sites at the protein surfaces in a set of user-supplied protein structures. Thus, this web server may help to detect potential off-target protein. It takes as input a protein complexed with a ligand and identifies within user-defined or predefined collections of protein structures, those having a binding site compatible with this ligand in terms of geometry and physicochemical properties. It is based on a non-sequential local alignment of the patch over the entire protein surface. Then the PatchSearch web server proposes a ligand binding mode for the potential off-target, as well as an estimated affinity calculated by the Vinardo scoring function. This novel tool is able to efficiently detects potential interactions of ligands with distant off-target proteins. Furthermore, by facilitating the discovery of unexpected off-targets, PatchSearch could contribute to the repurposing of existing drugs. The server is freely available at http://bioserv.rpbs.univ-paris-diderot.fr/services/PatchSearch.

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Figures

Figure 1.
Figure 1.
PatchSearch web server flowchart.
Figure 2.
Figure 2.
Visualization of hits in the PatchSearch web server. (A) results table of proteins with patches similar to a query patch. (B) NGL viewer displaying the retrieved patch for 1efp structure. The protein is in white cartoon, ligand in thick sticks with C atoms in cyan and the residues of the retrieved patch are represented in lines with C atoms in green.
Figure 3.
Figure 3.
The position of ADP, in sticks with C atoms in magenta, proposed by the PatchSearch web server and the experimental position of GNP, in sticks with C atoms in green, in the 4nym structure.
See this image and copyright information in PMC

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