Hydration and flexibility of α-, β-, γ- and δ-cyclodextrin: A molecular dynamics study

The conformational behaviour in vacuo and in explicit water, and the hydration of the macrocyclic oligosaccharides cyclodextrins (CDs) containing from six up to nine sugar rings have been studied by atomistic molecular dynamics simulations. CDs are relatively soluble in water, but show a hydrophobic cavity wherein they may host appropriate guests, thus acting as a carrier of lipophilic molecules in an aqueous environment. In this paper, we discuss the size and conformation of cyclodextrins, including in particular their flexibility in solution, and their hydration pattern through the description of clusters of water molecules included within the cavity, as observed experimentally in the crystalline state. The resulting picture allows a better understanding of the efficiency of these molecules to form host-guest adducts.