Theory of solutions in the energy representation. III. Treatment of the molecular flexibility

The method of energy representation for evaluating the solvation free energy is extended to a solute molecule with structural flexibility. When the intramolecular structure of the solute molecule exhibits a strong response to the solute–solvent interaction, the approximate functional for the solvation free energy needs to be modified from the original form presented previously [J. Chem. Phys. 117, 3605 (2002); 118, 2446 (2003)]. In the modification of the functional, the solvation-induced change in the distribution function of the solute structure is taken into account with respect to the intramolecular energy of the solute. It is then demonstrated over a wide range of thermodynamic conditions that the modified form of functional provides an accurate and efficient route to the solvation free energy of a flexible solute molecule even when the structural distribution function of the solute in solution overlaps barely with that of the solute at isolation.