The solutes were all modeled using the General AMBER Force Field version 2 (GAFF2) as implemented in the AMBER 20 simulation suite . Parameters were generated using antechamber and converted from AMBER to GROMACS format using ParmEd. To generate partial charges for each of the SAMPL7 solute molecules, we first took the Daylight SMILES provided by the challenge organizers and generated an initial 3-D structure with Open Babel 2.3.2 . Next, using Open Babel we performed a systematic conformation search to identify the lowest energy conformer followed by geometry optimization, all using the General Amber Force Field (GAFF) with Gasteiger partial charges as implemented in Open Babel. We then took the final structure for each compound from Open Babel and performed a geometry optimization in vacuum at the M06-2X/6-31+G** level of theory/basis set using Gaussian 16 . This was followed by a single point energy calculation at the HF/6-31G* level of theory/basis with Gaussian 16 to generate an electrostatic potential from which partial charges were obtained using the restrained electrostatic potential (RESP) method in antechamer (within the AMBER 20 simulation suite). The use of RESP with HF/6-31G* is based on the recommendations of the original GAFF work .