Abstract

Molecular dynamics (MD) simulations using the Amber force field have been
applied to obtain detailed information on inclusion complex formation
between natural cyclodextrins (CDs) and organic molecules (1-alkanols,
substituted phenols, and substituted imidazoles). The obtained MD
trajectories were used to estimate the binding free energy of each guest/CD
complex using the molecular mechanics/Poisson Boltzmann surface area
(MM-PBSA) method. The calculated relative binding free energies of the
inclusion complexes of some organic compounds with α- and β-CDs were in
good agreement with the experimental data though the absolute values
were not. Inspection of the binding free energy components revealed the
dominant contribution of van der Waals interactions to inclusion complex
stability. Both guest-host electrostatic interactions and the hydrophobic
effect do also contribute to complex stability. It was also apparent from the
calculations that the flexibility of the guest molecule has a significant
contribution to complex stability.