Peptide binding to β-cyclodextrins: structure, dynamics, energetics, and electronic effects

Area of Science:

• Computational Chemistry
• Supramolecular Chemistry
• Biophysics

Background:

• Peptide-cyclodextrin complexes are vital in pharmaceutical and food industries.
• Understanding structure-property relationships in these complexes is crucial but challenging.
• Experimental studies are abundant, yet molecular-level insights into structural changes remain limited.

Purpose of the Study:

• To investigate the structural and electronic modifications of peptides upon complexation with cyclodextrins.
• To elucidate the key interactions, preferred orientations, and energetic landscapes of peptide-cyclodextrin complexes.
• To analyze the impact of complex formation on peptide flexibility and local dipole moments.

Main Methods:

• Molecular dynamics (MD) simulations.
• Combined quantum mechanics-molecular mechanics (QM/MM) calculations.
• Analysis of backbone torsion angles, hydrogen bonding, and relative orientations.

Main Results:

• The most stable configuration places the peptide backbone near the narrow rim of beta-cyclodextrin (β-CD).
• Strong hydrogen bonds form between peptide NH groups and β-CD hydroxyl groups, reducing peptide flexibility.
• Complex formation increases the local dipole moment of the peptide by favoring specific C=O bond orientations.

Conclusions:

• Cyclodextrin complexation significantly alters peptide structure and dynamics.
• Observed changes in flexibility and dipole moment may influence peptide secondary structure.
• Theoretical calculations provide valuable insights into host-guest interactions at the molecular level.