One lesson is that careful system set-up is important, but not always straightforward even for systems thought to be simple. Part of the difficulty in this challenge was choosing microstate(s), and predicting and handling different potential binding poses when the binding mode(s) are not known. For example, there were questions on whether some of the WP6 carboxylate arms would remain protonated, thus reducing the WP6 formal charge from -12 to -10 or -8 or -6. The TFP guest had an additional nitrogen at its alkyl amine side chain, adding protonation states that may need to be considered. In addition, some guests had induced chirality at nitrogen centers, and unique enantiomers that may not interconvert at simulation timescales and perhaps needed to be considered. In these cases, methods varied in how they modeled the relevant protonation states of guests and hosts at experimental pH, and binding modes considered for calculations.