A Cavity Corrected 3D-RISM Functional for Accurate Solvation Free Energies

We show that an Ng
bridge function modified version of the three-dimensional
reference interaction site model (3D-RISM-NgB) solvation free energy
method can accurately predict the hydration free energy (HFE) of a
set of 504 organic molecules. To achieve this, a single unique constant
parameter was adjusted to the computed HFE of single atom Lennard-Jones
solutes. It is shown that 3D-RISM is relatively accurate at predicting
the electrostatic component of the HFE without correction but requires
a modification of the nonpolar contribution that originates in the
formation of the cavity created by the solute in water. We use a free
energy functional with the Ng scaling of the direct correlation function
[Ng, K. C. J. Chem. Phys. 1974, 61, 2680]. This produces a rapid, reliable small molecule
HFE calculation for applications in drug design.