As discussed in the previous section, this work proposes to use ensembles with hundreds of molecular dynamics simulations to compute ∆G bind , but the apparent ability to predict the slopes in the linear model presented in eq 4 for HP-β-CD offers a considerably reduction in the computational cost. In fact, because we did not observe a clear connection between the free energy of binding of native β-CD and log(P ) (Figure in the supporting information) the computational cost of applying the linear model presented above are simulations on guest molecules in complex with native β-CD to obtain ∆G 0 bind from eq 4. We have tested this model on IBU and KET which have comparable log(P ) values to ANS. From the log(P ) values listed in Table we obtain slopes (in units of kcal/mol/DS) for IBU of -0.57 and -0.52 for up and down, respectively, and for KET we obtain -0.54 and -0.49, respectively.