The few obvious outliers observed in Figure can be explained by the host-guest complex not forming a proper 1:1 inclusion complex during the 10 ns simulation. Instead, those outliers represent simulations where guest molecules are observed to be outside, or only partly inside the CD cavity during large parts of the simulations. For example, the annotated outlier for ANS only forms a proper inclusion complex in the last 10 % of the simulation and a predicted ∆G bind = -2.9 ± 4.0 kcal/mol. The outlier observed for PLM is found to only be outside the cavity and has a predicted ∆G bind = +2.3 ± 3.6 kcal/mol.