Predicting hydration free energies of the FreeSolv database of druglike molecules with molecular density functional theory

Abstract

We assess the performance of molecular densityfunctional theory (MDFT) to predict hydration freeenergies of the small drug-like molecules benchmark,FreeSolv. MDFT in the hyper-netted chain approx-imation (HNC) coupled with a pressure correctionpredicts experimental hydration free energies of theFreeSolv database within 1 kcal/mol with an averagecomputation time of two cpu.min per molecule. Thisis the same accuracy as for simulation based free en-ergy calculations that typically require hundreds ofcpu.h or tens of gpu.h per molecule.