PatchSearch: a web server for off-target protein identification

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


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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacteria / chemistry
  • Binding Sites
  • Databases, Chemical
  • Datasets as Topic
  • Drug Discovery
  • Drugs, Investigational / chemistry*
  • Drugs, Investigational / pharmacology
  • Humans
  • Internet
  • Ligands
  • Protein Binding
  • Protein Conformation, alpha-Helical
  • Protein Conformation, beta-Strand
  • Protein Interaction Domains and Motifs
  • Proteins / agonists
  • Proteins / antagonists & inhibitors
  • Proteins / chemistry*
  • Proteins / metabolism
  • Sequence Alignment
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / pharmacology
  • Software*


  • Drugs, Investigational
  • Ligands
  • Proteins
  • Small Molecule Libraries