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.
- Comparative modelling
- GABA receptor
- Ligand-gated ion channels (LGIC)
ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Computer Graphics and Computer-Aided Design
- Materials Chemistry