WATER-MEDIATED CONFORMATIONAL TRANSITIONS IN NICOTINIC RECEPTOR M2 HELIX BUNDLES - A MOLECULAR-DYNAMICS STUDY

The ion channel of the nicotinic acetylcholine receptor is a water-fil led pore formed by five M2 helix segments, one from each subunit. Mole cular dynamics simulations on bundles of five M2 alpha 7 helices surro unding a central column of water and with caps of water molecules at e ither end of the pore have been used to explore the effects of intrapo re water on helix packing, Interactions of water molecules with the N- terminal polar sidechains lead to a conformational transition from rig ht- to left-handed supercoils during these simulations, These studies reveal that the pore formed by the bundle of M2 helices is flexible, A structural role is proposed for water molecules in determining the ge ometry of bundles of isolated pore-forming helices.