title: Retinal Flip in Rhodopsin Activation?
abstract: Rhodopsin is a well-characterized structural model of a G protein-coupled receptor. Photoisomerization of the covalently bound retinal triggers activation. Surprisingly, the x-ray crystal structure of the active Meta-II state has a 180° rotation about the long-axis of the retinal polyene chain. Unbiased microsecond-timescale all-atom molecular dynamics simulations show that the retinal cofactor can flip back to the orientation observed in the inactive state of rhodopsin under conditions favoring the Meta-I state. Our results provide, to our knowledge, the first evidence from molecular dynamics simulations showing how rotation of the retinal ligand within its binding pocket can occur in the activation mechanism of rhodopsin.
authors.affiliation: The C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, West Virginia.
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona; Department of Physics, University of Arizona, Tucson, Arizona.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Brown
authors.affiliation: The C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, West Virginia. Electronic address: blake.mertz@mail.wvu.edu.
authors.forename: Blake
authors.initials: B
authors.lastname: Mertz
mesh_terms: D000595:Amino Acid Sequence; D008051:Lipid Bilayers / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D012243:Rhodopsin / Q000737:chemistry*; D012399:Rotation
chemical_list: D008051:Lipid Bilayers; D012243:Rhodopsin