title: Expanding the olfactory code by in silico decoding of odor-receptor chemical space.
abstract: Coding of information in the peripheral olfactory system depends on two fundamental : interaction of individual odors with subsets of the odorant receptor repertoire and mode of signaling that an individual receptor-odor interaction elicits, activation or inhibition. We develop a cheminformatics pipeline that predicts receptor-odorant interactions from a large collection of chemical structures (>240,000) for receptors that have been tested to a smaller panel of odorants (∼100). Using a computational approach, we first identify shared structural features from known ligands of individual receptors. We then use these features to screen in silico new candidate ligands from >240,000 potential volatiles for several Odorant receptors (Ors) in the Drosophila antenna. Functional experiments from 9 Ors support a high success rate (∼71%) for the screen, resulting in identification of numerous new activators and inhibitors. Such computational prediction of receptor-odor interactions has the potential to enable systems level analysis of olfactory receptor repertoires in organisms. DOI:http://dx.doi.org/10.7554/eLife.01120.001.
authors.affiliation: Genetics, Genomics, and Bioinformatics Program , University of California, Riverside , Riverside , United States.
authors.forename: Sean Michael
authors.initials: SM
authors.lastname: Boyle
authors.forename: Shane
authors.initials: S
authors.lastname: McInally
authors.forename: Anandasankar
authors.initials: A
authors.lastname: Ray
mesh_terms: D000818:Animals; D057506:Arthropod Antennae / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003198:Computer Simulation; D062126:Databases, Chemical; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation; D008024:Ligands; D008958:Models, Molecular; D009812:Odorants / Q000032:analysis*; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D018035:Receptors, Odorant / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D029721:Drosophila Proteins; D008024:Ligands; D018035:Receptors, Odorant; D054852:Small Molecule Libraries
keywords: D. melanogaster; antenna; cheminformatics; electrophysiology; odorant receptors