DYNAMIC PROPERTIES OF INDIVIDUAL WATER-MOLECULES IN A HYDROPHOBIC PORE LINED WITH ACYL CHAINS - A MOLECULAR-DYNAMICS STUDY

Recently, a certain class of synthetic molecules has been shown to for m ion channels, the pore of which is lined with hydrophobic acyl chain s [M. Sokabe, in: F. Oosawa, H. Hayashi, T. Yoshioka (Eds.), Transmemb rane Signaling and Sensation, JSSP/VNU Science Press BV, Tokyo, 1984, p. 119; F. Hayashi, M. Sokabe, M. Takagi, K. Hayashi, U. Kishimoto, Bi ochim. Biophys. Acta, 510 (1978) 305; M.J. Pregel, L. Jullien, J. Canc eill, L. Lacombe, J.M. Lehn, J. Chem. Sec. Perkin Trans., 2 (1995) 417 ; Y. Tanaka, Y. Kobuke, M. Sokabe, Angew. Chem. Int. Ed. Engl., 34 (19 95) 693; M. Sokabe, Z. Qi, K. Donowaki, H. Ishida, K. Okubo, Biophys. J., 70 (1996) A201; Ii. Ishida, K. Donowaki, Y. Inoue, Z. Qi, M. Sokab e, Chem. Lett. (1997) p. 953]. As an initial step towards understandin g the physical mechanisms of ion permeation across such a hydrophobic pore, systematic molecular dynamics simulations were performed to inve stigate dynamic and energetic properties of water molecules inside the pore using a dimer of alanine-N'-acylated cyclic peptide as a channel model. Dynamic energy profiles for water molecules indicated that the energy barrier at the middle region of the pore is approximately 2-3 kcal/mol higher than that in the cap water region which was defined as a vicinity region of the channel entrance. Energetics analyses demons trated that the mutual interactions among intrapore water molecules ar e the major factor to give favorable interaction (negative energy cont ribution) for themselves. The pore, despite being lined with acyl chai ns, has a favorable van der Waals interaction with intrapore water mol ecules. These results may help to explain why water-filled channels ca n be formed by the hydrophobic helices in natural channels. (C) 1998 E lsevier Science B.V.