A model for the GABAa receptor has been developed based on the recent  crystal structure of the Glutamate-gated ligand-gated ion channel from  C. Elegans. Interactions with lipophilic modulators, particularly the  anesthetic isoflurane and the neurosteroid pregnenolone, have been  investigated using a combination of atomistic molecular dynamics and  alchemical free energy perturbation. Affinities of these modulators for  several putative inter and intrasubunit sites will be presented. Details  of the molecular interactions with high affinity sites will be  discussed, including the significance of hydrogen bonding interactions  in stabilizing pregnenolone/neurosteroid contacts. Results are  consistent with multi-site mechanisms for both isoflurane and  pregnenolone.

Interactions of inhaled and endogenous anesthetics with the GABA<sub>A</sub> receptor

243rd National Meeting (2012)

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Interactions of inhaled and endogenous anesthetics with the GABAA receptor

Interactions of inhaled and endogenous anesthetics with the GABA_A receptor