Relating protein pharmacology by ligand chemistry
- PMID: 17287757
- DOI: 10.1038/nbt1284
Relating protein pharmacology by ligand chemistry
Abstract
The identification of protein function based on biological information is an area of intense research. Here we consider a complementary technique that quantitatively groups and relates proteins based on the chemical similarity of their ligands. We began with 65,000 ligands annotated into sets for hundreds of drug targets. The similarity score between each set was calculated using ligand topology. A statistical model was developed to rank the significance of the resulting similarity scores, which are expressed as a minimum spanning tree to map the sets together. Although these maps are connected solely by chemical similarity, biologically sensible clusters nevertheless emerged. Links among unexpected targets also emerged, among them that methadone, emetine and loperamide (Imodium) may antagonize muscarinic M3, alpha2 adrenergic and neurokinin NK2 receptors, respectively. These predictions were subsequently confirmed experimentally. Relating receptors by ligand chemistry organizes biology to reveal unexpected relationships that may be assayed using the ligands themselves.
Similar articles
-
Off-target networks derived from ligand set similarity.Methods Mol Biol. 2009;575:195-205. doi: 10.1007/978-1-60761-274-2_8. Methods Mol Biol. 2009. PMID: 19727616
-
Domain-based small molecule binding site annotation.BMC Bioinformatics. 2006 Mar 17;7:152. doi: 10.1186/1471-2105-7-152. BMC Bioinformatics. 2006. PMID: 16545112 Free PMC article.
-
Real spherical harmonic expansion coefficients as 3D shape descriptors for protein binding pocket and ligand comparisons.Bioinformatics. 2005 May 15;21(10):2347-55. doi: 10.1093/bioinformatics/bti337. Epub 2005 Feb 22. Bioinformatics. 2005. PMID: 15728116
-
Automatic annotation of protein function.Curr Opin Struct Biol. 2005 Jun;15(3):267-74. doi: 10.1016/j.sbi.2005.05.010. Curr Opin Struct Biol. 2005. PMID: 15922590 Review.
-
Computational chemistry approaches to drug discovery in signal transduction.Biotechnol J. 2008 Apr;3(4):452-70. doi: 10.1002/biot.200700259. Biotechnol J. 2008. PMID: 18412174 Review.
Cited by
-
Comparison of ultra-fast 2D and 3D ligand and target descriptors for side effect prediction and network analysis in polypharmacology.Br J Pharmacol. 2013 Oct;170(3):557-67. doi: 10.1111/bph.12294. Br J Pharmacol. 2013. PMID: 23826885 Free PMC article.
-
ChemProt-2.0: visual navigation in a disease chemical biology database.Nucleic Acids Res. 2013 Jan;41(Database issue):D464-9. doi: 10.1093/nar/gks1166. Epub 2012 Nov 26. Nucleic Acids Res. 2013. PMID: 23185041 Free PMC article.
-
Detection of drug-drug interactions by modeling interaction profile fingerprints.PLoS One. 2013;8(3):e58321. doi: 10.1371/journal.pone.0058321. Epub 2013 Mar 8. PLoS One. 2013. PMID: 23520498 Free PMC article.
-
N-1,2,3-Triazole-isatin derivatives: anti-proliferation effects and target identification in solid tumour cell lines.RSC Med Chem. 2022 Jun 10;13(8):970-977. doi: 10.1039/d2md00044j. eCollection 2022 Aug 17. RSC Med Chem. 2022. PMID: 36092141 Free PMC article.
-
EFMSDTI: Drug-target interaction prediction based on an efficient fusion of multi-source data.Front Pharmacol. 2022 Sep 23;13:1009996. doi: 10.3389/fphar.2022.1009996. eCollection 2022. Front Pharmacol. 2022. PMID: 36210804 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
