Because partial charge generation does not scale well with increasing numbers of atoms in a molecule, we sought to reduce the computational cost of this study by truncating uninteresting functional groups (and in particular, functional groups unlikely to impact the electrostatics of the remaining sca old) from our molecules to reduce molecular size and the number of possible conformations, at least if truncated molecules still maintained the same level of partial charge variation. We defined uninteresting functional groups as those which should have little conformational variation when charged, such as phenyl groups or symmetric aromatic rings. Because the HIF2a ligands were particularly large and flexible which led to slow conformer generation and time-consuming charge assignments, we sought to truncate these molecules (while checking to ensure that the same issues still persisted) to identify more minimal versions which could be treated more rapidly while preserving the same issues. Each of the molecules were visually inspected for a functional group that could easily be truncated across a single bond based on our criteria. We only truncated the HIF2a molecules. Using an rdkit v2024.03.2 EditableMolecule we removed the functional group at the specified bond and added hydrogens to complete the valence of the atoms on the remaining molecule. The truncated HIF2a molecules were used in place of the original HIF2a molecules for the remainder of our study (SI Figure , SI Figure ).