Force Field Parameterization for the Description of the Interactions between Hydroxypropyl-β-Cyclodextrin and...

Area of Science:

• Computational Chemistry
• Biophysics
• Materials Science

Background:

• Cyclodextrins, particularly hydroxypropyl-β-cyclodextrin (HPβCD), are versatile excipients in pharmaceutical formulations.
• Understanding HPβCD's molecular behavior is crucial for optimizing its use as a drug carrier and solubilizer.

Purpose of the Study:

• To develop and validate accurate all-atom simulation parameters for HPβCD.
• To investigate HPβCD's interactions with water and amino acids at a molecular level.

Main Methods:

• Development of HPβCD simulation parameters based on the ADD force field.
• Comparison with the CHARMM36 force field using Kirkwood-Buff integrals for HPβCD-water mixtures.
• Molecular dynamics simulations to analyze HPβCD interactions with individual amino acids.

Main Results:

• The ADD-based force field significantly improves the prediction of HPβCD self-association and water interactions compared to CHARMM36.
• HPβCD exhibits strong interactions with both polar and nonpolar amino acid residues, especially aromatic ones.
• Simulations reveal a preferential orientation of HPβCD's cavity towards amino acid backbones.

Conclusions:

• The refined ADD-based parameters provide a more accurate molecular-level description of HPβCD.
• HPβCD's interactions with amino acids suggest a potential for protein denaturation.
• These findings can guide the development of HPβCD-based drug delivery systems and therapeutic strategies.