Free-energy analysis of the binding into membrane with the method of energy representation

Nobuyuki Matubayasi, Wataru Shinoda, and Masaru Nakahara

J. Chem. Phys. 128, 195107 (2008).

A statistical-mechanical treatment of the binding into membrane is presented in combination with molecular simulation. The membrane solution is viewed as an inhomogeneous, mixed solvent system, and the method of energy representation is employed to calculate the free energy of solvation of a solute in the membrane with a realistic set of potential functions. Carbon monoxide, benzene, and ethylbenzene are adopted as model solutes to analyze the binding into 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) membrane. The solvation free energy is obtained in the hydrophobic, glycerol, and headgroup regions, and the membrane inside is shown to be more favorable than the bulk water. The distribution of the solute is found to be rather diffuse throughout the membrane inside. The membrane-water partition coefficient is then evaluated with the help of the Kirkwood-Buff theory, and the performance of the method is assessed. The partial contributions from DMPC and water to the solvation thermodynamics are formally identified within the approximate formulation, and the role of the repulsive and attractive interactions is discussed.