β-Cyclodextrin/propiconazole Complexes Probed by Constraint Free and Biased Molecular Dynamics Simulations

Cyclodextrins are widely used nowadays in many fields, including therapeutic systems, due to their ability to form inclusion complexes with a wide variety of compounds. In this study we present a series of molecular dynamics (MD) simulations on beta-cydodextrin/propiconazole inclusion complexes in order to gain insights on the inclusion process. The data obtained from constraint-free molecular dynamics simulations revealed spontaneous complexation processes resulting in several geometries with small differences in the free energy of binding, which are predicted to co-exist in aqueous solution. Semiempirical quantum mechanical computations (PM3) were also performed in gas phase on the MD obtained complexes and the results could be at least qualitatively correlated with the MD findings. However, the lack of explicit solvent representation in PM3 calculations can constitute a major drawback in evaluating the relative energies of complexation of different inclusion modes.