Implicit Solvation - Accessible Surface Area-based Method

Accessible Surface Area-based Method

The free energy of solvation of a solute molecule in the simplest ASA-based method is given by:

where is accessible surface area of atom i, and is solvation parameter of atom i, i.e. a contribution to the free energy of solvation of the particular atom i per surface unit area. The required solvation parameters for different types of atoms (C, N, O, S, etc.) are usually determined by least squares fit of the calculated and experimental transfer free energies for a series of organic compounds. The experimental energies are determined from partition coefficients of these compounds between different solutions or media using standard mole concentrations of the solutes.

It is noteworthy that solvation energy is free energy required to transfer a solute molecule from a solvent to “vacuum” (gas phase). This solvation energy can supplement the intramolecular energy in vacuum calculated in molecular mechanics. Therefore, the required atomic solvation parameters were initially derived from water-gas partition data. However, the dielectric properties of proteins and lipid bilayers are much more similar to those of nonpolar solvents than to vacuum. Newer parameters have therefore been derived from water-octanol partition coefficients or other similar data. Such parameters actually describe transfer energy between two condensed media or the difference of two solvation energies.