Constrained geometric simulation of the nicotinic acetylcholine receptor

•Used first/froda to simulate dynamics of the nicotinic acetylcholine receptor.•Studied links between acetylcholine binding pocket and the transmembrane gate.•Lateral communication mediated by a “conformational wave”.•Key residues for inter-subunit communication identified.

Constrained geometric simulations have been performed for the recently published closed-channel state of the nicotinic acetylcholine receptor. These simulations support the theory that correlated motion in the flexible β-sheet structure of the extracellular domain helps to communicate a “conformational wave”, spreading from the acetylcholine binding pocket. Furthermore, we have identified key residues that act at the interface between subunits and between domains that could potentially facilitate rapid communication between the binding site and the transmembrane gate.

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