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Structure‐based discovery of new chemotypes conferring new biology
Author(s) -
Shoichet Brian
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.524.1
Subject(s) - chemotype , computational biology , biology , degeneracy (biology) , binding site , small molecule , drug discovery , docking (animal) , chemistry , bioinformatics , biochemistry , medicine , food science , essential oil , nursing
Receptor binding sites are evolved to recognize a few endogenous ligands, but the degeneracy of molecular recognition ensures that multiple other ligands and chemotypes can bind to the same site. Sometimes these non‐biological molecules will confer activities that the native ligands do not. Structure‐based docking is a fruitful way to find such novel ligands, by screening large libraries of compounds for new chemotypes that physically complement a binding site, but do not resemble the endogenous ligands. If these searches are coupled to the right biological assays, they can find new molecules conferring unprecedented biology. This will be illustrated with a screen for novel agonists of the m‐opioid receptor. New opportunities arising from a great increase in the number of available, interesting molecules, now well‐over 10 8 of which are readily available and dockable, will be considered. Support or Funding Information Supported by GM71896 and GM106990