Accelerated diffusion of Na+ in a hydrophobic region revealed by moleculardynamics simulations of a synthetic ion channel

To get insight into the significance of the hydrophobic lining on the ion p ermeation, we performed molecular dynamics simulations on a Na+ permeation through a de novo synthetic hydrophobic channel. Electrophysiological study has suggested that the channel is formed from a tail-to-tail associated di mer of a cyclic octa-peptide coupled with hydrophobic acyl chains. The acyl chains line the channel pore while the cyclic peptide forms the channel en trance [Z. Qi, M. Sokabe, K. Donowaki, H. Ishida, Biophys. J. 76 (1999) 631 ]. Molecular dynamics simulation of water in the channel indicated that the inferred structure is physically reasonable [Z. Qi, M. Sokabe, Biophys. Ch em. 71 (1998) 35]. In the present study, the potential energy profile of th e Na+ and the energy contributions from each component of the system at dif ferent positions along the channel axis were calculated. An energy well ins tead of a peak is located at the central hydrophobic cavity of the channel, due to its ability of accommodating at least five water molecules to hydra te the ion. Interestingly, the ion diffuses much faster in the hydrophobic acyl chain region, particularly in the central hydrophobic cavity, than it does in the peptide ring region and even surprisingly faster than that in t he bulk phase. These results provide a physical basis for an idea that the hydrophobic lining of the K+ channel [D.A. Doyle, J.M. Cabral, R.A. Pfuetzn er, A. Kuo, J.M. Gulbis, S.L. Cohen, B.T. Chait, R. MacKinnon, Science 280 (1998) 69] plays an active role to facilitate the ion permeation through th e channel pore. (C) 1999 Elsevier Science B.V. All rights reserved.