Accurate prediction of hydration free energies and solvation structures using molecular density functional theory with a simple bridge functional

Daniel Borgis (1, 2) , Sohvi Luukkonen (1) , Luc Belloni (3) , Guillaume Jeanmairet (4, 5)

1 MDLS - Maison de la Simulation
2 PASTEUR - Processus d'Activation Sélective par Transfert d'Energie Uni-électronique ou Radiatif (UMR 8640)
3 LIONS - Laboratoire Interdisciplinaire sur l'Organisation Nanométrique et Supramoléculaire
4 PHENIX - PHysicochimie des Electrolytes et Nanosystèmes InterfaciauX
5 RS2E - Réseau sur le stockage électrochimique de l'énergie

This paper assesses the ability of molecular density functional theory to predict efficiently and accurately the hydration free energies of molecular solutes and the surrounding microscopic water structure. A wide range of solutes were investigated, including hydrophobes, water as a solute, and the FreeSolv database containing 642 drug-like molecules having a variety of shapes and sizes. The usual second-order approximation of the theory is corrected by a third-order, angular-independent bridge functional. The overall functional is parameter-free in the sense that the only inputs are bulk water properties, independent of the solutes considered. These inputs are the direct correlation function, compressibility, liquid–gas surface tension, and excess chemical potential of the solvent. Compared to molecular simulations with the same force field and the same fixed solute geometries, the present theory is shown to describe accurately the solvation free energy and structure of both hydrophobic and hydrophilic solutes. Overall, the method yields a precision of order 0.5 kBT for the hydration free energies of the FreeSolv database, with a computer speedup of 3 orders of magnitude. The theory remains to be improved for a better description of the H-bonding structure and the hydration free energy of charged solutes.

Domaines: Chimie théorique et/ou physique

Daniel Borgis, Sohvi Luukkonen, Luc Belloni, Guillaume Jeanmairet. Accurate prediction of hydration free energies and solvation structures using molecular density functional theory with a simple bridge functional. Journal of Chemical Physics, 2021, 155 (2), pp.024117. ⟨10.1063/5.0057506⟩. ⟨hal-03454131⟩