Movement of Small Molecules in Lipid Bilayers: Molecular Dynamics Simulation Studies

Abstract

To assist in understanding the mechanism of membrane permeation, the movement of four different molecules within hydrated lipid bilayer membranes were studied via over 15 nanoseconds of atomic-level molecular dynamics simulation. In particular, the simulations were used to explain the anomolously high rate of permeation seen for small molecules. These simulations support the hypothesis that the rate of diffusion of small solutes is enhanced because they can move rapidly within and jump between spontaneously arising voids. The enhanced diffusion rate is greatest in the bilayer center where the voids are most frequently found and of the largest size. Molecules the volume of benzene or smaller experience this enhanced movement, however larger molecules, those the size of adamantane or larger, do not. The details of the diffusional mechanisms of these molecules are discussed. The role of hydrogen bonding for the interactions between drugs (a nifedipine analog) and membranes is discussed.