Ab Initio Evaluation of Complexation Energies for Cyclodextrin-Drug Inclusion Complexes

[Image: see text] We investigated the reliability of ab initio methods to predict the binding energies of molecular encapsulation complexes. Vast possibilities for the docking conformations were screened down to a couple of geometries using a semiempirical docking simulation. For the candidates, we applied density functional theory (DFT) with several exchange–correlation (XC) functionals to evaluate the binding energy. We carefully selected and compared the functionals to elucidate the role of the characteristic factors in achieving the XC effects. It is clarified that the improper combination in XC with D3 dispersion force correction leads to overbinding. For achieving a proper combination, the exchange interaction over the longer range to avoid the overbinding was found to be important.