To apply SMIRNOFF99Frosst parameters, we followed a multistep process, beginning with the AMBERformat .prmtop and .inpcrd GAFF v1.7 files. The host and guest molecules were parameterized with version 0.0.3 of the Open Force Field Toolkit which uses the OpenEye OEChem Toolkit version 2.0.2 , which reads molecular coordinates and topologies and creates a serialized representation of the molecular system; version 1.0.5 of the SMIRNOFF99Frosst force field; specified in version 1.0 of the SMIRNOFF format. Once parameterized with SMIRNOFF99Frosst, the topology and coordinates for the host-guest complex were combined with the solvent and ions, which retained their TIP3P water parameters and Joung-Cheatham ion parameters, respectively. This was accomplished by the ParmEd program , which enables saving the OpenMM system created by the Open Force Field Toolkit in AMBER-format .prmtop and .inpcrd files. Ongoing updates to the Open Force Field Toolkit may result in changes to how this procedure is carried out in the future.