کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5371266 | 1503945 | 2012 | 10 صفحه PDF | دانلود رایگان |

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 15Â ns in an MD run. TYR450 seemed to regulate the orientation of the glutamate upon binding by cation-Ï 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.
Highlights⺠Unbiased MD simulations reveal the spontaneous glutamate-binding and cleft-closing mechanisms. ⺠The glutamate is attracted by ARG485 to enter the cleft from a more flexible side without the SS bond. ⺠The orientation of the glutamate upon binding is regulated by TYR450 with the cation-Ï interaction. ⺠A semi-open state is identified in the free energy profile obtained by the unbiased MD simulations. ⺠The so-called linear response theory is verified in the inter-domain motion of the LBD of GluR2.
Journal: Biophysical Chemistry - Volume 162, March 2012, Pages 35-44