Small molecule hydration energy and entropy from 3D-RISM

Abstract

Implicit solvent models offer an attractive way to estimate the effects of a solvent environment on the properties of small or large solutes without the complications of explicit simulations. One common test of accuracy is to compute the free energy of transfer from gas to liquid for a variety of small molecules, since many of these values have been measured. Studies of he temperature dependence of these values (i.e. solvation enthalpies and entropies) can provide additional insights into the performance of implicit solvent models. Here, we show how to compute temperature derivatives of hydration free energies for the 3D-RISM integral equation approach. Results for 1123 small drug-like molecules (both neutral and charged) in water are compared to results from molecular dynamics simulations and to experiment. The uncorrected results are rather poor, but it is known that errors are strongly correlated with the partial molar volumes of the solutes. We examine several linear solvation Gibbs energy correction schemes and extend them to deal with solvation ethalpies and entropies.

Closure for the Ornstein-Zernike equation with pressure and free energy consistency

“…is not satisfied, then Eqs. (27) and (28) are not equivalent and may not agree with other expressions for the chemical potential. For example, HNC exhibits Gibbs-Duhem consistency when the viral pressure is used, Eq.…”

“…All closures display inconsistency between the virial and compressibility expressions for Gibbs-Duhem, Eqs. (27) and Eq. (28).…”

“…Some physical insight to can be gained by comparing our new closure to the various partial molar volume based corrections that have been proposed for 3D-RISM theory and molecular density functional theory (MDFT) [24][25][26][27]. These are modifications to the usual closure specific expressions for the chemical potential and are not bridge corrections.…”

“…From this interpretation, we have a ′ = P contact /ρ. Due to pressure inconsistencies in HNC, P contact is not equal to the virial or compressibility pressure but is the contact pressure between the solute and solvent [27,50,51]. Like the virial and compressibility pressures, the contact pressure for HNC is too high and corrections like UC are employed to compensate for this.…”

“…However, these closures do not display pressure consistency and both pressure and free energy estimates are inaccurate [23]. In fact, to compensate for the large errors, a number of partial molar volume (PMV) corrections have been developed that are applied to just the chemical potential [24][25][26][27].…”