Structure and dynamics of β-cyclodextrin in aqueous solution at the density-functional tight binding level

Structure and dynamics of beta-cyclodextrin (beta-CyD), a prototype host for inclusion compounds of biological interest, is investigated by means of density-functional based tight-binding molecular dynamics (MD) simulations. The computational protocol is benchmarked against available experimental data and first-principles calculations. Solvent-solute interactions, including the diffusion into and dwell time of the solvent in the cavity of beta-CyD, are studied with a hybrid QM/MM method. Comparison of MD simulations of beta-CyD in the gas phase and in water shows that the solvent reduces the flexibility of the structure framework, while the terminal hydroxyl groups become more flexible and are embedded in a network of hydrogen bonds. Our 160 ps MD simulations, provide enough sampling to discuss the dynamics of the water inside the cavity. The dwell time of the encapsulated water molecule has a wide distribution with a peak at 70 fs. Surprisingly, despite only the 17% difference between the "top" and "bottom" opening area of the beta-CyD cone, 64% of the water molecules enter the cavity through the slightly bigger "bottom" aperture.