In Figure we present computed ∆G bind for the four molecules MCH, PLM, ANS and CHL in complex with HP-β-CD as a function of increasing degree of substitution. Generally, ∆G bind decreases by 10.4 kcal/mol from -0.9 kcal/mol to -11.3 kcal/mol as the degree of substitution is increased. We observe similar decreases in ∆G bind of 12.2 kcal/mol, 14.4 kcal/mol and 20.3 kcal/mol for PLM, ANS and CHL, respectively. We observe that the larger molecular log(P ) is, the more beneficial (lower ∆G bind ) it is for molecules to be encapsulated in the HP-β-CD cavity as expected. The standard deviations of the binding free energies are observed (Figure in the supporting information) to increase from around 2 kcal/mol to roughly 5 kcal/mol as the degree of substitution is increased. This is not unexpected because the structural flexibility is increased by adding more substituted 2hydroxypropyl side chains and thus additional sampling is required to keep the uncertainty in ∆G bind constant.