Ion Permeation through a Phospholipid Membrane: Transition State, Path Splitting, and Calculation of Permeability.

We investigate the thermodynamics and kinetics of the permeation of a potassium ion through a phospholipid membrane. We illustrate that the conventional reaction coordinate (the position of the ion along the normal to the membrane plane) is insufficient to capture essential elements of the process. It is necessary to add coarse variables that measure membrane distortion. New coarse variables are suggested, and a two-dimensional coarse-space is proposed to describe the permeation. We illustrate path splitting and two transition states of comparable barrier heights. The alternative pathways differ by the extent of water solvation of the ion-phosphate pairs. The permeation process cannot be described by a local one-dimensional reaction coordinate, and a network formulation is more appropriate. We use Milestoning with Voronoi tessellation in two dimensions to quantify the equilibrium and rate of the permeation of the positively charged ion. The permeation coefficient is computed and compared favorably to experiment.