A generalized G-SFED continuum solvation free energy calculation model

Significance This paper deals with a long-standing problem in biophysics, which is resolved here. The model has a strong physical background and will have a wide range of applications to physical and biological problems. The model proposed in this article, GSFED model, can be used for the solvation free energy calculation of most organic solutes in most organic solvents. Since the computing time depends linearly on the size of the molecule, the model can be applied easily to large molecules, for example proteins. The model can provide reliable salvation free energies of experimentally unavailable solute-solvent pairs. An empirical continuum solvation model, solvation free energy density (SFED), has been developed to calculate solvation free energies of a molecule in the most frequently used solvents. A generalized version of the SFED model, generalized-SFED (G-SFED), is proposed here to calculate molecular solvation free energies in virtually any solvent. G-SFED provides an accurate and fast generalized framework without a complicated description of a solution. In the model, the solvation free energy of a solute is represented as a linear combination of empirical functions of the solute properties representing the effects of solute on various solute–solvent interactions, and the complementary solvent effects on these interactions were reflected in the linear expansion coefficients with a few solvent properties. G-SFED works well for a wide range of sizes and polarities of solute molecules in various solvents as shown by a set of 5,753 solvation free energies of diverse combinations of 103 solvents and 890 solutes. Octanol-water partition coefficients of small organic compounds and peptides were calculated with G-SFED with accuracy within 0.4 log unit for each group. The G-SFED computation time depends linearly on the number of nonhydrogen atoms (n) in a molecule, O(n).

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