Molecular interactions of flavonoids to pepsin: Insights from spectroscopic and molecular docking studies

• The inhibitory effects of 10 flavonoids on pepsin were measured in vitro.
• Binding mechanisms were investigated by spectroscopic and docking methods.
• Pepsin fluorescence was quenched via static quenching with r less than 7 nm.
• The interaction of Pepsin with flavonoids occurred in the hydrophobic cavity.
• The common residues lining the flavonoids in the catalytic site were investigated.

In the work described on this paper, the inhibitory effect of 10 flavonoids on pepsin and the interactions between them were investigated by a combination of spectroscopic and molecular docking methods. The results indicated that all flavonoids could bind with pepsin to form flavonoid–pepsin complexes. The binding parameters obtained from the data at different temperatures revealed that flavonoids could spontaneously interact with pepsin mainly through electrostatic forces and hydrophobic interactions with one binding site. According to synchronous and three-dimensional fluorescence spectra and molecular docking results, all flavonoids bound directly into the enzyme cavity site and the binding influenced the microenvironment and conformation of the pepsin activity site which resulted in the reduced enzyme activity. The present study provides direct evidence at a molecular level to understand the mechanism of digestion caused by flavonoids.

The complex was formed by non-covalent reactions between flavonoids (baicalein here) and pepsin, which resulted in the significant decrease in the fluorescence intensity of pepsin. The molecular docking study shows that flavonoids are located in the hydrophobic cavity of pepsin. Since the binding of flavonoids affected the microenvironment of the pepsin activity site, flavonoids caused the inhibition of pepsin activity.Figure optionsDownload as PowerPoint slide