Molecular dynamics simulations of ion channels formed by bundles of amphipathic α-helical peptides

Ion channels may be formed by self-assembly of amphipathic α-helical peptides into parallel helix bundles. The transbilayer pores formed by such peptides contain extended columns of water molecules, the properties of which may differ from those of water in its bulk state. The de novo designed peptides of DeGrado et al., which contain only leucine and serine residues, are considered as a simple example of such channels. Molecular dynamics simulations of peptide helix bundles with water molecules within and at the mouths of their pores are used to refine such models and to investigate the properties of intra-pore water. The translational and rotational mobility of water molecules within the pores are reduced relative to bulk water. Furthermore, intra-pore waters orient themselves with their dipoles anti-parallel to the helix dipoles, as do the hydroxyl groups of serine residues. Comparison of approximate predictions of ionic conductances with experimental values provides support for the validity of these models.