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Deciphering the Binding Mode of Zolpidem to GABAA α1 Receptor – Insights from Molecular Dynamics Simulation

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Title Deciphering the Binding Mode of Zolpidem to GABAA α1
Receptor – Insights from Molecular Dynamics Simulation
 
Creator .Vijayan, R.S K
Bhattacharyya, Dhananjay
Ghoshal, Nanda
 
Subject Structural Biology & Bioinformatics
 
Description To investigate the binding mode of Zolpidem to
GABAA and to delineate the conformational changes
induced upon agonist binding, we carried out atomistic
molecular dynamics simulation using the ligand binding
domain of GABAA α1 receptor. Comparative molecular
dynamics simulation of the apo and the holo form of
GABAA receptor revealed that γ2/α1 interface housing the
benzodiazepine binding site undergoes distinct conformational
changes upon Zolpidem binding. We notice that C
loop of the α1 subunit experiences an inward motion
toward the vestibule and the F loop of γ2 sways away from
the vestibule, an observation that rationalizes Zolpidem as
an alpha1 selective agonist. Energy decomposition analysis
carried out was able to highlight the important residues
implicated in Zolpidem binding, which were largely in
congruence with the experimental data. The simulation
study disclosed herein provides a meaningful insight into
Zolpidem-GABAAR interactions and helps to arrive at a
binding mode hypothesis with implications for drug design.
 
Publisher Springer Verlag
 
Date 2012
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1486/1/APPLIED_BIOCHEMISTRY_AND_BIOTECHNOLOGY___166(_8_)1991%2D2006;2012[26].pdf
.Vijayan, R.S K and Bhattacharyya, Dhananjay and Ghoshal, Nanda (2012) Deciphering the Binding Mode of Zolpidem to GABAA α1 Receptor – Insights from Molecular Dynamics Simulation. Journal of Molecular Modeling, 28 (4). pp. 1345-1354.
 
Relation http://dx.doi.org/10.1007/s00894-011-1142-0
http://www.eprints.iicb.res.in/1486/