Exploring host-guest complexation mechanisms by a molecular dynamics/quantum mechanics/continuum solvent model approach

We introduce a molecular dynamics/quantum mechanics/continuum solvent model (MD/QM/6SM) approach to investigate binding mechanisms of host-guest systems. The representative conformations of host, guest, and their complex generated from MD simulations at the molecular-mechanics level are used for binding free energy calculations based on a QM/CSM model. We use this approach to explore the binding mechanisms of,8-cyclodextrin (beta-CD) and 2, 6-di-methyl-beta-CD (DM-beta-CD) with various guest molecules. Our results suggest that solvent effects play a more important role in determining the relative binding affinities of DM-beta-CD than those of beta-CD mainly because the former is more flexible than the latter. (C) 2016 Elsevier B.V. All rights reserved.