Pores Formed by the Nicotinic Receptor M2 δ Peptide: A Molecular Dynamics Simulation Study

Abstract

The M2 δ peptide self-assembles to form a pentameric bundle of transmembrane α-helices that is a model of the pore-lining region of the nicotinic acetylcholine receptor. Long (>15 ns) molecular dynamics simulations of a model of the M2 δ 5 bundle in a POPC bilayer have been used to explore the conformational dynamics of the channel assembly. On the timescale of the simulation, the bundle remains relatively stable, with the polar pore-lining side chains remaining exposed to the lumen of the channel. Fluctuations at the helix termini, and in the helix curvature, result in closing/opening transitions at both mouths of the channel, on a timescale of ∼10 ns. On average, water within the pore lumen diffuses ∼4× more slowly than water outside the channel. Examination of pore water trajectories reveals both single-file and path-crossing regimes to occur at different times within the simulation.