A comparative analysis of models for hydration free energy calculations using the RISM theory of integral equations

Rigorous calculations and a detailed analysis of the free energies of hydration were performed using the RISM (reference interaction site model) approach for 96 compounds of various chemical natures. A comparison of all the existing models for calculation of hydration free energy, including models that use corrections and semiempirical parameters, was performed for the first time. The applicability ranges of all the models under consideration were determined. It was shown that the PWC model based on jointly using the RISM and chemoinformatics approaches gave most accurate hydration free energy values. This model allows the free energy of hydration to be predicted with high accuracy and, at the same time, does not require the use of substantial computer resources.