The phenothiazine moiety of TFP, CPZ, and TDZ had functionalization, thus, these substituents would also occupy distinct primary and secondary face orientations giving rise to separate binding modes (see Figure ). In addition, the nitrogen on the phenothiazine moiety of TFP, CPZ, and TDZ undergoes induced chirality, so binding modes to account for these conformational enantiomers may also be necessary. Considering all primary and secondary face orientations due to the asymmetric nature of these host-guest systems, the number of binding modes that may not interconvert or sampled with some methods becomes 8. Indeed, the top performing ATM/FFENGINE/TIP3P/HREM method did exactly that (while also accommodating for guests with multiple protomer states) with success.