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The nicotinic acetylcholine receptor is an integral membrane protein and a ligand-gated cation channel. It has stoichiometry alpha 2 beta gamma delta, the subunits arranged symmetrically around an approximate five-fold axis. Five M2 helices, one from each subunit, form a parallel helix bundle surrounding a central pore. Simulated annealing via restrained molecular dynamics (SA/MD) has been employed to generate ensembles of isolated M2 transmembrane helices. Four ensembles of two different M2 helix sequences, M2 delta and M2 gamma, have been generated by SA/MD. The ensembles differed in their treatment of electrostatic interactions. Analysis of the simulated structures showed that intra-helical H-bonds were more strongly conserved in the C-terminal (and more hydrophobic) segment of M2 helices. Conformations of polar sidechains have been analyzed, placing particular emphasis on EK (and QK) pairs at the N-termini of M2 delta (and M2 gamma) helices. Conformations of EK sidechain pairs were obtained for the high resolution structures in the protein database in order to guide our analysis of simulated structures. Serine and threonine sidechain conformations in the M2 models also have been determined. Implications of studies of isolated M2 helices for models of the intact pore region of the nicotinic receptor are discussed.


Journal article


Biophys Chem

Publication Date





215 - 230


Amino Acid Sequence, Animals, Computer Simulation, Enzymes, Macromolecular Substances, Models, Molecular, Molecular Sequence Data, Protein Structure, Secondary, Proteins, Receptors, Nicotinic, Torpedo