Simulation of the passive permeation of potassium ion through phospholipid membranes: Thermodynamics and kinetics

Here we revisit the problem of passive ion permeation through a phospholipid membrane and find new rich mechanisms that were not captured in earlier investigations by introducing new coarse variables. Numerous experimental and simulation studies have been performed on passive permeation through membranes. Most of simulation studies only consider one reaction coordinate that is the vertical position of the center of mass of the permeant with respect to the center of mass of the membrane. However, when the permeant is positively charged, it interacts stronlgy with the phosphate groups and permeation is accompanied by significant distortions of the membrane. To model ther distortion of the membrane, we introduce two new coarse variables: the minimal distances of the positively charged group from the phosphate groups of each leaflet. We illustrate the efficiency of this new set of coarse variables on permeation of a single potassium ion. Using Milestoning, we were able to calculate free energy landscape, mean first passage time, and the permeability of the ion in the space of the two new coarse variables. The results compared favorably to the available experimental data.