@article {662, title = {Mechanisms of Passive Ion Permeation through Lipid Bilayers: Insights from Simulations}, journal = {J Phys Chem B}, volume = {110}, number = {42}, year = {2006}, note = {Tepper, Harald L Voth, Gregory A 1 S10 RR17214-01/RR/NCRR NIH HHS/United States R01 GM053148/GM/NIGMS NIH HHS/United States R01 GM053148-05/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov{\textquoteright}t Research Support, U.S. Gov{\textquoteright}t, Non-P.H.S. United States The journal of physical chemistry. B J Phys Chem B. 2006 Oct 26;110(42):21327-37.}, pages = {21327-37}, abstract = {

Multistate empirical valence bond and classical molecular dynamics simulations were used to explore mechanisms for passive ion leakage through a dimyristoyl phosphatidylcholine lipid bilayer. In accordance with a previous study on proton leakage (Biophys. J. 2005, 88, 3095), it was found that the permeation mechanism must be a highly concerted one, in which ion, solvent, and membrane coordinates are coupled. The presence of the ion itself significantly alters the response of those coordinates, suggesting that simulations of transmembrane water structures without explicit inclusion of the ionic solute are insufficient for elucidating transition mechanisms. The properties of H(+), Na(+), OH(-), and bare water molecules in the membrane interior were compared, both by biased sampling techniques and by constructing complete and unbiased transition paths. It was found that the anomalous difference in leakage rates between protons and other cations can be largely explained by charge delocalization effects rather than the usual kinetic picture (Grotthuss hopping of the proton). Permeability differences between anions and cations through phosphatidylcholine bilayers are correlated with suppression of favorable membrane breathing modes by cations.

}, keywords = {Computer Simulation Dimyristoylphosphatidylcholine Ions/*pharmacokinetics Kinetics Lipid Bilayers/*metabolism Permeability Solvents}, doi = {10.1021/jp064192h}, author = {H. L. Tepper and G. A. Voth} }