Molecular simulation of nonfacilitated membrane permeation.

This is a review. Non-electrolytic compounds typically cross cell membranes by passive diffusion. The rate of permeation is dependent on the chemical properties of the solute and the composition of the lipid bilayer membrane. Predicting the permeability coefficient of a solute is important in pharmaceutical chemistry and toxicology. Molecular simulation has proven to be a valuable tool for modeling permeation of solutes through a lipid bilayer. In particular, the solubility-diffusion model has allowed for the quantitative calculation of permeability coefficients. The underlying theory and computational methods used to calculate membrane permeability are reviewed. We also discuss applications of these methods to examine the permeability of solutes and the effect of membrane composition on permeability. The application of coarse grain and polarizable models is discussed. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov.