title: How broadly tuned olfactory receptors equally recognize their agonists. Human OR1G1 as a test case.
abstract: The molecular features that dominate the binding mode of agonists by a broadly tuned olfactory receptor are analyzed through a joint approach combining cell biology, calcium imaging, and molecular modeling. The odorant/receptor affinities, estimated through statistics accrued during molecular dynamics simulations, are in accordance with the experimental ranking. Although in many systems receptors recognize their target through a network of oriented interactions, such as H-bonding, the binding by broadly tuned olfactory receptors is dominated by non-polar terms. We show how such a feature allows chemicals belonging to different chemical families to similarly activate the receptors through compensations of interactions within the binding site.
authors.affiliation: Institut de Chimie de Nice, UMR CNRS, Université de Nice Sophia Antipolis 7272, 06108 Nice Cedex 2, France.
authors.forename: Landry
authors.initials: L
authors.lastname: Charlier
authors.forename: Jérémie
authors.initials: J
authors.lastname: Topin
authors.forename: Catherine
authors.initials: C
authors.lastname: Ronin
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Kim
authors.forename: William A
authors.initials: WA
authors.lastname: Goddard
authors.forename: Roman
authors.initials: R
authors.lastname: Efremov
authors.forename: Jérôme
authors.initials: J
authors.lastname: Golebiowski
mesh_terms: D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D018035:Receptors, Odorant / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D012903:Smell / Q000502:physiology
chemical_list: D008024:Ligands; C533784:OR1G1 protein, human; D018035:Receptors, Odorant; D002118:Calcium