MOLECULAR-DYNAMICS SIMULATIONS OF ION CHANNELS FORMED BY BUNDLES OF AMPHIPATHIC ALPHA-HELICAL PEPTIDES

Ion channels may be formed by self-assembly of amphipathic alpha-helic al peptides into parallel helix bundles. The transbilayer pores formed by such peptides contain extended columns of water molecules, the pro perties of which may differ from those of water in its bulk state. The de novo designed peptides of DeGrado et al., which contain only leuci ne and serine residues, are considered as a simple example of such cha nnels. Molecular dynamics simulations of peptide helix bundles with wa ter molecules within and at the mouths of their pores are used to refi ne such models and to investigate the properties of intra-pore water. The translational and rotational mobility of water molecules within th e pores are reduced relative to bulk water. Furthermore, intra-pore wa ters orient themselves with their dipoles anti-parallel to the helix d ipoles, as do the hydroxyl groups of serine residues. Comparison of ap proximate predictions of ionic conductances with experimental values p rovides support for the validity of these models.