An alamethicin channel in a lipid bilayer: Molecular dynamics simulations

We present the results of 2-ns molecular dynamics (MD) simulations of a hexameric bundle of Aim helices in a 1-palmitoyl-2-oleoylphosphatidylcholine bilayer. These simulations explore the dynamic properties of a model of a helix bundle channel in a complete phospholipid bilayer in an aqueous environment. We explore the stability and conformational dynamics of the bundle in a phospholipid bilayer. We also investigate the effect on bundle stability of the ionization state of the ring of Glu(18) side chains. If all of the Glu(18) side chains are ionised, the bundle is unstable; if none of the Glu(18) side chains are ionized, the bundle is stable. pK(A) calculations suggest that either zero or one ionized Glu(18) is present at neutral pH, correlating with the stable form of the helix bundle. The structural and dynamic properties of water in this model channel were examined. As in earlier in vacuo simulations (Breed et al., 1996. Biophys. J. 70:1643-1661), the dipole moments of water molecules within the pore were aligned antiparallel to the helix dipoles. This contributes to the stability of the helix bundle.