Given the importance of interactions between PET and enzymes, we evaluated the interactions between BHET and common protein functional groups to guarantee self-consistency between our parameters and the Drude force field. As shown in Figure and 2C, benzene (BENZ) stacking interactions with BHET are slightly underestimated, with maximum errors of ∼1.5 and ∼1.4 kcal/mol for sandwich and T-shape stacking interactions, respectively. Ethane (ETHA) interactions (Figure ) were also well captured, with a similar interaction energy minimum distance, and well depth difference of less than 0.5 kcal/mol. For methylguanidinium (MGUAN) interactions (Figure ), the minimum distance was shifted slightly outward in our Drude model, suggesting a slight repulsion in the MM model relative to the QM calculations for distances shorter than 3.5 Å. Nevertheless, the magnitude of the interaction energy minimum was well captured, suggesting that cation-π interactions with our PET model should be reasonably represented. In addition, we considered N-methylacetamide (NMA) interactions with the carbonyl oxygen as a model for the well-known σ-hole interactions observed in PET hydrolases. To do so, we scanned the interaction of NMA along both the carbonyl bond axis and at an angle similar to that observed for σ-hole interactions. In both cases, the energy profiles yielded by Drude were able to reproduce both the QM minimum distance and the well depth accurately (Figure and). Finally, we also scanned the interaction of a water molecule perpendicular to the BHET ring plane to assess whether solvent interactions would be correctly captured.