Free-energy analysis of binding functions of soft molecular aggregates on the basis of the extended concept of solvation

Abstract

The free-energy analysis is essential to understand and control a chemical process in condensed phase. The current status of theoretical/computation chemistry is, however, that the free energy remains a most difficult quantity to compute. For fast and accurate computation of the free energy with its molecular understanding, a new theory of solutions has been combined with molecular simulation. This theory is called the method of energy representation, and constructs the solvation free energy as a functional of distribution functions of the solute-solvent pair interaction energy. The method of energy representation greatly expands the scope of solution theory, and is amenable to such frontline topics of physical chemistry and biophysics as supercritical fluid, flexible molecules with intramolecular degrees of freedom, inhomogeneous system, and quantum-mechanical/molecular-mechanical (QM/MM) system. In fact, the binding of a molecule into such molecular-aggregate systems as solution, lipid membrane, and micelle can be viewed as solvation in an extended sense, and the method of energy representation can provide the free energy of solvation in the extended sense; the strength and site of binding are determined from calculations of the solvation free energy. We present a brief introduction to the free-energy calculation in solution, and introduce an application to a lipid-membrane system. The membrane is treated as an inhomogeneous, mixed solvent system consisting of water and an amphiphilic molecule, and the binding of a hydrophobic solute into it is analyzed with the combination of the molecular simulation and the energy-representation method. The solvation free energy is determined as a function of the binding depth, and the common role of water is pointed out under densityvariable conditions such as the membrane/water interface, air/water interface, and supercritical water.