MOLECULAR-DYNAMICS SIMULATIONS OF WATER WITHIN MODELS OF ION CHANNELS

The transbilayer pores formed by ion channel proteins contain extended columns of water molecules. The dynamic properties of such waters hav e been suggested to differ from those of water in its bulk state. Mole cular dynamics simulations of ion channel models solvated within and a t the mouths of their pores are used to investigate the dynamics and s tructure of intra-pore water. Three classes of channel model are inves tigated: a) parallel bundles of hydrophobic (Ala(10)) alpha-helices; b ) eight-stranded hydrophobic (Ala(10)) antiparallel beta-barrels; and c) parallel bundles of amphipathic alpha-helices (namely, delta-toxin, alamethicin, and nicotinic acetylcholine receptor M2 helix). The self -diffusion coefficients of water molecules within the pores are reduce d significantly relative to bulk water in all of the models. Water rot ational reorientation rates are also reduced within the pores, particu larly in those pores formed by alpha-helix bundles. In the narrowest p ore (that of the Ala(20) pentameric helix bundle) self-diffusion coeff icients and reorientation rates of intra-pore waters are reduced by ap proximately an order of magnitude relative to bulk solvent. In Ala(20) helix bundles the water dipoles orient antiparallel to the helix dipo les. Such dipole/dipole interaction between water and pore may explain how water-filled ion channels may be formed by hydrophobic helices. I n the bundles of amphipathic helices the orientation of water dipoles is modulated by the presence of charged side chains. No preferential o rientation of water dipoles relative to the pore axis is observed in t he hydrophobic beta-barrel models.