Exploring ligand recognition and ion flow in comparative models of the human GABA type A receptor

Younes Mokrab, Vassiliy N. Bavro, Kenji Mizuguchi, N. P. Todorov, Ian L. Martin, Susan M.J. Dunn, S. L. Chan, P. L. Chau

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

We present two comparative models of the GABAA receptor. Model 1 is based on the 4-Å resolution structure of the nicotinic acetylcholine receptor from Torpedo marmorata and represents the unliganded receptor. Two agonists, GABA and muscimol, two benzodiazepines, flunitrazepam and alprazolam, together with the general anaesthetic halothane, have been docked to this model. The ion flow is also explored in model 1 by evaluating the interaction energy of a chloride ion as it traverses the extracellular, transmembrane and intracellular domains of the protein. Model 2 differs from model 1 only in the extracellular domain and represents the liganded receptor. Comparison between the two models not only allows us to explore commonalities and differences with comparative models of the nicotinic acetylcholine receptor, but also suggests possible protein sub-domain interactions with the GABAA receptor not previously addressed.

Original languageEnglish
Pages (from-to)760-774
Number of pages15
JournalJournal of Molecular Graphics and Modelling
Volume26
Issue number4
DOIs
Publication statusPublished - Nov 2007
Externally publishedYes

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Keywords

  • Alprazolam
  • Benzodiazepine
  • Comparative modelling
  • Docking
  • Flunitrazepam
  • GABA
  • GABA receptor
  • Halothane
  • Ligand-gated ion channels (LGIC)
  • Muscimol

ASJC Scopus subject areas

  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Computer Graphics and Computer-Aided Design
  • Materials Chemistry

Cite this

Mokrab, Y., Bavro, V. N., Mizuguchi, K., Todorov, N. P., Martin, I. L., Dunn, S. M. J., Chan, S. L., & Chau, P. L. (2007). Exploring ligand recognition and ion flow in comparative models of the human GABA type A receptor. Journal of Molecular Graphics and Modelling, 26(4), 760-774. https://doi.org/10.1016/j.jmgm.2007.04.012