Abstract
Solvation free energy is a fundamental thermodynamic quantity that should be determined to estimate various physicochemical properties of a molecule and the desolvation cost for its binding to macromolecular receptors. Here, we propose a new solvation free energy function through the improvement of the solvent-contact model, and test its applicability in estimating the solvation free energies of organic molecules with varying sizes and shapes. This new solvation free energy function is constructed by combining the existing solute-solvent interaction term with the self-solvation term that reflects the effects of intramolecular interactions on solvation. Four kinds of atomic parameters should be determined in this solvation model: atomic fragmental volume, maximum atomic occupancy, atomic solvation, and atomic self-solvation parameters. All of these parameters for total 37 atom types are optimized by the operation of a standard genetic algorithm in such a way to minimize the difference between the experimental solvation free energies and those calculated by the solvation free energy function for 362 organic molecules. The solvation free energies estimated from the new solvation model compare well with the experimental results with the associated squared correlation coefficients of 0.88 and 0.85 for training and test sets, respectively. The present solvation model is thus expected to be useful for estimating the solvation free energies of organic molecules.
Highlights
Solvation free energy serves as a characteristic property of various molecules in material, biological, and pharmaceutical sciences
Prior to the calculation of solvation free energies of 404 organic molecules, their geometries were fully optimized at B3LYP/6-31G* level of theory from the initial structures generated with the CORINA program
The improvement in the accuracy could be attributed to the inclusion of the self-solvation term in the solvation free energy function and to the extension of the atom types to cope with a variety of chemical environments
Summary
Solvation free energy serves as a characteristic property of various molecules in material, biological, and pharmaceutical sciences. More precise methods for predicting molecular solvation free energies than the dielectric continuum models were suggested on the basis of the Poisson-Boltzmann equation to calculate the electrostatic potentials around the solute molecule [7]. These implicit solvation models were incapable of reflecting the solute-solvent interactions on atomic scale, which has an effect of limiting the reliabilities of the calculated molecular solvation free energies. As a compromise between the computational cost and the accuracy, a variety of efficient computational methods with reasonable accuracy have been proposed based on various theoretical frameworks such as solvent-accessible surface area model [20,21], 3-D reference interaction site model [22], cellular automata based algorithm [23], quantitative structure– property relationship (QSPR) model [24], linear interaction energy method [25], and quantum mechanical continuum solvation models [26]
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