Insights into the Interaction between Polyphenols and β-Lactoglobulin through Molecular Docking, MD Simulation, and QM/MM Approaches

Abstract

In this work, we have explored the interaction of three different polyphenols with the food protein β-lactoglobulin. Antioxidant activities of polyphenols are influenced by complexation with the protein. However, studies have shown that polyphenols after complexation with the protein can be more beneficial due to enhanced antioxidant activities. We have carried out molecular docking, molecular dynamics (MD) simulation, and quantum mechanics/molecular mechanics (QM/MM) studies on the three different protein–polyphenol complexes. We have found from molecular docking studies that apigenin binds in the internal cavity, luteolin binds at the mouth of the cavity, and eriodictyol binds outside the cavity of the protein. Docking studies have also provided binding free energy and inhibition constant values that showed that eriodictyol and apigenin exhibit better binding interactions with the protein than luteolin. For eriodictyol and luteolin, van der Waals, hydrophobic, and hydrogen bonding interactions are the main interacting forces, whereas for apigenin, hydrophobic and van der Waals interactions play major roles. We have calculated the root mean square deviation (RMSD), root mean square fluctuations (RMSF), solvent-accessible surface area (SASA), interaction energies, and hydrogen bonds of the protein–polyphenol complexes. Results show that the protein–eriodictyol complex is more stable than the other complexes. We have performed ONIOM calculations to study the antioxidant properties of the polyphenols. We have found that apigenin and luteolin act as better antioxidants than eriodictyol does on complexation with the protein, which is consistent with the results obtained from MD simulations.

Anti-Inflammatory Effects of Dietary Polyphenols through Inhibitory Activity against Metalloproteinases

“…Further advances in technology and research are expected to continue to unravel the detailed interaction between polyphenols and MMPs. The use of emerging computational technologies including quantum mechanical/molecular mechanical simulations [ 152 , 153 ], may enhance our understanding of precise binding modes and complexation between polyphenols and MMPs.…”

Freeze-dried persimmon peel: A potential ingredient for functional ice cream

“…Furthermore, a number of proteins interact with phenolic compounds and affect milk product properties [ 64 ]. Several studies have demonstrated that proteins can bind to phenolic compounds [ [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] ]. Protein structure can be altered by phenolic compounds binding to proteins, thus affecting availability of certain amino acids [ 75 ].…”

Food Antioxidants and Their Interaction with Human Proteins

“…Likewise, a protein can bind different antioxidants at different sites. For example, β-lactoglobulin (BLG) binds apigenin in the internal cavity, luteolin at the entrance of the cavity, and eriodictyol outside the cavity [ 29 ].…”