Molecular Recognition by beta-Cyclodextrin Derivatives: FEP vs MM / PBSA Study

The complexation of p-tert-butylphenyl p-tert-butylbenzoate, N- (p-tert-butylphenyl)-p-tert-butylbenzamide and a bisadamantyl-phosphate derivative with a beta-cyclodextrin derivative formed by two cyclodextrin units linked by a disulfide bridge on one of the C6 atoms have been studied by computational methods (free energy perturbation (FEP) and Molecular Mechanics / Poisson Bolzmann Surface Area (MM / PBSA)). The calculated relative free energies of the amide and ester are in good agreement with experiment only for MM / PBSA and not for FEP. Only MM / PBSA was applied to the bisadamantyl-phosphate complex and its calculated association free energy was calculated to be similar to that of the ester, which is consistent with the experimental tendencies.