Simulation Parameters. All molecular dynamics (MD) production runs were done using GROMACS 2021.2. The TIP4P force field was used for water with a 3 nm cubic box since there is no dependence on the box size when simulating the solvation free energy. The density of toluene in toluene was calculated and yielded approximately 150 toluene molecules for the size of the box; the appropriate toluene force field was found via the CHARMM-GUI when generating simulation boxes. Force fields for the challenge molecules were generated using the CHARMM General Force Field (CGenFF) with the DFT-optimized structures as input structures. All simulations were set to an equilibrium temperature of 300 K and a pressure of 1 atm.