PatchSearch: a web server for off-target protein identification.
Amino Acid Sequence
Animals
Bacteria
/ chemistry
Binding Sites
Databases, Chemical
Datasets as Topic
Drug Discovery
Drugs, Investigational
/ chemistry
Humans
Internet
Ligands
Protein Binding
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
Protein Interaction Domains and Motifs
Proteins
/ agonists
Sequence Alignment
Small Molecule Libraries
/ chemistry
Software
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
02 07 2019
02 07 2019
Historique:
accepted:
21
05
2019
revised:
26
04
2019
received:
22
02
2019
pubmed:
28
5
2019
medline:
19
5
2020
entrez:
28
5
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31131411
pii: 5498752
doi: 10.1093/nar/gkz478
pmc: PMC6602448
doi:
Substances chimiques
Drugs, Investigational
0
Ligands
0
Proteins
0
Small Molecule Libraries
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
W365-W372Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
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