Molecular dynamics simulations for glutamate-binding and cleft-closing processes of the ligand-binding domain of GluR2

Okimasa Okada, Kei Odai, Tohru Sugimoto, Etsuro Ito

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)35-44
Number of pages10
JournalBiophysical Chemistry
Volume162
DOIs
Publication statusPublished - 2012 Mar
Externally publishedYes

Fingerprint

Molecular Dynamics Simulation
Molecular dynamics
Glutamic Acid
Ligands
Computer simulation
Ion Channel Gating
Ionotropic Glutamate Receptors
Ion Channels
Free energy
Cations
Hydrogen
Hydrogen bonds

Keywords

  • Free energy profile
  • Glutamate binding pathway
  • Inter-domain conformational change
  • Semi-open state
  • Unbiased molecular dynamics simulation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Organic Chemistry

Cite this

Molecular dynamics simulations for glutamate-binding and cleft-closing processes of the ligand-binding domain of GluR2. / Okada, Okimasa; Odai, Kei; Sugimoto, Tohru; Ito, Etsuro.

In: Biophysical Chemistry, Vol. 162, 03.2012, p. 35-44.

Research output: Contribution to journalArticle

@article{07106368fd2c422da92dc17b9ac760fa,
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.",
keywords = "Free energy profile, Glutamate binding pathway, Inter-domain conformational change, Semi-open state, Unbiased molecular dynamics simulation",
author = "Okimasa Okada and Kei Odai and Tohru Sugimoto and Etsuro Ito",
year = "2012",
month = "3",
doi = "10.1016/j.bpc.2011.12.004",
language = "English",
volume = "162",
pages = "35--44",
journal = "Biophysical Chemistry",
issn = "0301-4622",
publisher = "Elsevier",

}

TY - JOUR

T1 - Molecular dynamics simulations for glutamate-binding and cleft-closing processes of the ligand-binding domain of GluR2

AU - Okada, Okimasa

AU - Odai, Kei

AU - Sugimoto, Tohru

AU - Ito, Etsuro

PY - 2012/3

Y1 - 2012/3

N2 - 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.

AB - 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.

KW - Free energy profile

KW - Glutamate binding pathway

KW - Inter-domain conformational change

KW - Semi-open state

KW - Unbiased molecular dynamics simulation

UR - http://www.scopus.com/inward/record.url?scp=84857372724&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84857372724&partnerID=8YFLogxK

U2 - 10.1016/j.bpc.2011.12.004

DO - 10.1016/j.bpc.2011.12.004

M3 - Article

C2 - 22284903

AN - SCOPUS:84857372724

VL - 162

SP - 35

EP - 44

JO - Biophysical Chemistry

JF - Biophysical Chemistry

SN - 0301-4622

ER -