Disassembling solvation free energies into local contributions-Toward a microscopic understanding of solvation processes

Solvation free energies contribute to the driving force of molecular processes in solution and play a significant role for the relative stability of biomolecular conformations or the formation of complexes. Changes in solvation free energy are the origin of solvent-mediated interactions such as the hydrophobic effect in water. However, an accurate description of solvation free energies, specifically in aqueous solution, without explicit representation of the solvent is a challenging task in computer simulations. To improve existing models detailed microscopic information on solute-solvent interactions is required, which is not directly accessible from experiments. Explicit solvent simulations include solvent-mediated effects, however, at a considerable computational cost. Computational tools have been proposed in recent years to extract information on solvation free energies and solute-solvent interactions from explicit solvent simulations. The latter includes spatial decompositions of the solvation enthalpy and entropy, which may eventually lead to an improved theoretical understanding of solvation thermodynamics.