Fast Computation of Solvation Free Energies with Molecular Density Functional Theory: Thermodynamic-Ensemble Partial Molar Volume Corrections.

Molecular density functional theory (MDFT) offers an efficient implicit-solvent method to estimate molecule solvation free-energies, whereas conserving a fully molecular representation of the solvent. Even within a second-order approximation for the free-energy functional, the so-called homogeneous reference fluid approximation, we show that the hydration free-energies computed for a data set of 500 organic compounds are of similar quality as those obtained from molecular dynamics free-energy perturbation simulations, with a computer cost reduced by 2-3 orders of magnitude. This requires to introduce the proper partial volume correction to transform the results from the grand canonical to the isobaric-isotherm ensemble that is pertinent to experiments.

3DRISM Multigrid Algorithm for Fast Solvation Free Energy Calculations.

In this paper we present a fast and accurate method for modeling solvation properties of organic molecules in water with a main focus on predicting solvation (hydration) free energies of small organic compounds. The method is based on a combination of (i) a molecular theory, three-dimensional reference interaction sites model (3DRISM); (ii) a fast multigrid algorithm for solving the high-dimensional 3DRISM integral equations; and (iii) a recently introduced universal correction (UC) for the 3DRISM solvation free energies by properly scaled molecular partial volume (3DRISM-UC, Palmer et al., J.

Multigrid solver for the reference interaction site model of molecular liquids theory.

In this article, we propose a new multigrid-based algorithm for solving integral equations of the reference interactions site model (RISM). We also investigate the relationship between the parameters of the algorithm and the numerical accuracy of the hydration free energy calculations by RISM. For this purpose, we analyzed the performance of the method for several numerical tests with polar and nonpolar compounds.

An accurate prediction of hydration free energies by combination of molecular integral equations theory with structural descriptors.

In this work, we report a novel method for the estimation of the hydration free energy of organic molecules, the structural descriptors correction (SDC) model. The method is based on a combination of the reference interaction site model (RISM) with several empirical corrections. The model requires only a small number of chemical descriptors associated with the main features of the chemical structure of solutes: excluded volume, branch, double bond, benzene ring, hydroxyl group, halogen atom, aldehyde group, ketone group, ether group, and phenol fragment.

Accurate calculations of the hydration free energies of druglike molecules using the reference interaction site model.

We report on the results of testing the reference interaction site model (RISM) for the estimation of the hydration free energy of druglike molecules. The optimum model was selected after testing of different RISM free energy expressions combined with different quantum mechanics and empirical force-field methods of structure optimization and atomic partial charge calculation. The final model gave a systematic error with a standard deviation of 2.