Self-assembled mechanism of hydrophobic amino acids and β-cyclodextrin based on experimental and computational methods

The beta-cyclodextrin (beta-CD) can be used to remove bitter taste of protein hydrolysates, which is attributed to its interaction with hydrophobic amino acids included within peptides. But the corresponding mechanism has not been fully clarified. Herein, we systematically investigate the interaction between beta-CD and three hydrophobic amino acids involving tryptophan (Trp), tyrosine (Tyr), and phenylalanine (Phe). We prove the formation of amino acid/beta-CD supermolecular complexes determined by FS, UV, IR, DSC and NMR, manifesting that no new chemical bond is formed in these complexes. The theoretical interaction conformations are given by molecule docking and further supported by ONIOM (our Own N-layer Integrated Orbital molecular Mechanics) calculations, with the consideration of structural assignments, binding orientations, solvent effects, interaction energies and main forces to form these complexes. Molecular docking results suggest that the hydrophobic amino acids prefer to interact with beta-CD by their aromatic ring, meaning hydrophobic interactions are main forces for them entering into the cavity of beta-CD. ONIOM-based calculations provide a number of quantum-chemical parameters to confirm our experimental results; meanwhile, to demonstrate that H-bonds play an important role in maintaining the stability of three amino acid/beta-CD complexes. This work is help for demonstrating the interaction mechanism of amino acid/beta-CD supermolecular system, and guiding how to remove bitterness or undesirable taste of bioactive peptides, even other interested molecules.