Abstract: Cyclodextrin (CD) can form inclusion complexes with the guest molecule through supramolecular interaction, preserving or even enhancing the properties of the guest molecule. Molecular simulation is an important research tool to explore the interaction of CD with the guest molecule, which has been widely used in research on cyclodextrin inclusion reaction. In this paper, a brief overview of molecular simulations including quantum mechanics, molecular docking and molecular dynamics simulation was given, and the basic principles of and mainstream software and commonly used force fields for molecular docking and molecular dynamic simulation were summarized. Moreover, recent progresses on their application in cyclodextrin inclusion research were reviewed from four aspects: characterization of molecular structure changes, characterization of intermolecular interaction, solvent effects and synergistic stabilization. Research results show that the size of the hydrophobic cavity and the initial orientation of the guest within the cavity have very important effects on the structure of guest/cyclodextrin inclusion complexes; van der Waals interactions are the major driving force for the cyclodextrin inclusion reaction, and the formation of intermolecular hydrogen bonds is an important factor for the stability of the inclusion complex. The explicit solvent model is a powerful tool to study the solvent effect of the cyclodextrin inclusion reaction. Finally, the authors believe that molecular simulation will be useful for further investigations of the cyclodextrin inclusion process from the perspectives of multi-scale phenomena and machine learning.

Key words: cyclodextrin; encapsulation reaction; molecular docking; molecular dynamics simulation; interaction; multi-scale