First principles binding energy evaluation of host-guest inclusion complexes

Molecular capsulation is a key technique for biopharmaceuticals. The development of molecular capsules from the theory side requires a precise evaluation of binding energy between capsules and biopharmaceutical molecules. For this purpose, density functional theory (DFT) is a suitable evaluation method due to its good balance of calculation accuracy and cost. However, it is not straightforward to accurately evaluate van der Waals and exchange interactions using a pure exchange-correlation functional. Meanwhile, empirical corrections are known to significantly improve the accuracy. In this work, we benchmark CAM and D3 corrections applied to the B3LYP functional for the binding energy between plumbagin and cyclodextrins (β-cyclodextrin/methyl-β-cyclodextrin/2-O-hydroxypropyl-β-cyclodextrin). We calculate the reference binding energy by diffusion Monte Carlo (DMC) method. DMC accurately evaluates dispersion force without any practical approximations, unlike DFT. Both B3LYP and CAM-B3LYP give almost zero binding energies (i.e., do not reproduce binding). On the other hand, B3LYP-D3 and CAM-B3LYP-D3 give similar binding energies to DMC due to the D3 correction [1]. In this talk, we will also discuss the solvent effects on the binding energies.