Molecular dynamics of synthetic leucine-serine ion channels in a phospholipid membrane

Molecular dynamics calculations were carried out on models of two synthetic leucine-serine ion channels: a tetrameric bundle with sequence (LSLLLSL)(3 )NH2 and a hexameric bundle with sequence (LSSLLSL)(3)NH2. Each protein bun dle is inserted in a palmitoyloleoylphosphatidylcholine bilayer membrane an d solvated by simple point charge water molecules inside the pore and at bo th mouths. Both systems appear to be stable in the absence of an electric f ield during the 4 ns of molecular dynamics simulation. The water motion in the narrow pore of the four-helix bundle is highly restricted and may provi de suitable conditions for proton transfer via a water wire mechanism. In t he wider hexameric pore, the water diffuses much more slowly than in bulk b ut is still mobile. This, along with the dimensions of the pore, supports t he observation that this peptide is selective for monovalent cations. Reaso nable agreement of predicted conductances with experimentally determined va lues lends support to the validity of the simulations.