Posted by This study presents a comprehensive analysis of the cholesterol binding mechanism and conformational changes in cyclodextrin (CD) carriers, namely βCD, 2HPβCD, and MβCD. The results revealed that the binding of cholesterol to CDs was spontaneous and thermodynamically favorable, with van der Waals interactions playing a dominant role, while Coulombic interactions have a negligible contribution. The solubility of cholesterol/βCD and cholesterol/MβCD complexes was lower compared to cholesterol/2HPβCD complex due to stronger vdW and Coulombic repulsion between water and CDs. Hydrogen bonding was found to have a minor role in the binding process. The investigation of mechanisms and kinetics of binding demonstrated that cholesterol permeates into the CD cavities completely. Replicas consideration indicated that while the binding to 2HPβCD occurred perpendicularly and solely through positioning cholesterol’s oxygen toward the primary hydroxyl rim (PHR), the mechanism of cholesterol binding to βCD and MβCD could take place with the orientation of oxygen towards both rims. Functionalization resulted in decreased cavity polarity, increased constriction tendency, and altered solubility and configuration of the carrier. Upon cholesterol binding, the CDs expanded, increasing the cavity volume in cholesterol-containing systems.
Snapshots of the initial and final configurations of cholesterol toward βCD (a), MβCD (b), and 2HPβCD (c).
Ganjali Koli, M., Fogolari, F. Exploring the role of cyclodextrins as a cholesterol scavenger: a molecular dynamics investigation of conformational changes and thermodynamics. Sci Rep 13, 21765 (2023). https://doi.org/10.1038/s41598-023-49217-8