  The hydration or binding free energy of a drug-like molecule is a key data
for early stage drug discovery. Hundreds of thousands of evaluations are
needed, which rules out the exhaustive use of atomistic simulations and free
energy methods. Instead, the current docking and screening processes are today
relying on numerically efficient scoring functions that lose much of the atomic
scale information and hence remain error-prone. In this article, we show how a
probabilistic description of molecular liquids as implemented in the molecular
density functional theory predicts hydration free energies of a
state-of-the-art benchmark of small drug-like molecules within 0.5 kJ/mol (0.1
kcal/mol) of atomistic simulations, along with water and polarization maps, for
a computation time compatible with screening and docking.
