title: Molecular dynamics simulations for glutamate-binding and cleft-closing processes of the ligand-binding domain of GluR2.
abstract: The gating of ion channel of ionotropic glutamate receptors is controlled by the structural change of the ligand-binding domain of GluR2. We examined the roles of residues in the glutamate-binding and cleft-closing mechanisms by molecular dynamics (MD) simulations. A glutamate entered the cleft deeply within the order of nanoseconds and the cleft locked the glutamate completely at 15 ns in an MD run. TYR450 seemed to regulate the orientation of the glutamate upon binding by cation-π interaction. A semi-open state was identified in the free energy profile evaluated with the structures on the spontaneously glutamate-bound and cleft-closed pathway by the unbiased MD simulations for the first time to our knowledge. In the semi-open state, the two sub-domains were bridged by two hydrogen bonds of GLU705 in the sub-domain 2 with TYR732 in the sub-domain 1 and with the glutamate bound to the sub-domain 1 until the transition to the closed state.
authors.affiliation: ZoeGene Corporation, Yokohama, Kanagawa, Japan. Okada.Okimasa@mc.mt-pharma.co.jp
authors.forename: Okimasa
authors.initials: O
authors.lastname: Okada
authors.forename: Kei
authors.initials: K
authors.lastname: Odai
authors.forename: Tohru
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Etsuro
authors.initials: E
authors.lastname: Ito
mesh_terms: D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D018698:Glutamic Acid / Q000378:metabolism*; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D051381:Rats; D018091:Receptors, AMPA / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D018091:Receptors, AMPA; D018698:Glutamic Acid; C104722:glutamate receptor ionotropic, AMPA 2