Molecular dynamics simulations of dihydro-β-erythroidine bound to the human α4β2 nicotinic acetylcholine receptor.

Our model suggests that the side chains of α4 L257 (9') and α4 L264 (16') are the main constrictions in the transmembrane pore. The involvement of position 9' in channel gating is well established, but position 16' was only previously identified as a gate for the bacterial channels, ELIC and GLIC. L257 but not L264 was found to influence the slow component of desensitisation. The structure of the antagonist-bound state proposed here should be valuable for the development of therapeutic or insecticide compounds.