High-potency olfactory receptor agonists discovered by virtual high-throughput screening: molecular probes for receptor structure and olfactory function.

ABSTRACT: The detection of diverse chemical structures by the vertebrate olfactory system is accomplished by the recognition of odorous ligands by their cognate receptors. In the present study, we used computational screening to discover novel high-affinity agonists of an olfactory G protein-coupled receptor that recognizes amino acid ligands. Functional testing of the top candidates validated several agonists with potencies higher than any of the receptor's known natural ligands. Computational modeling revealed molecular interactions involved in ligand binding and further highlighted interactions that have been conserved in evolutionarily divergent amino acid receptors. Significantly, the top compounds display robust activities as odorants in vivo and include a natural product that may be used to s

SUBMITTER: Triballeau N 

PROVIDER: S-EPMC2652502 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature