Investigate the binding of catechins to trypsin using docking and molecular dynamics simulation

Area of Science:

• Biochemistry
• Molecular Biology
• Nutraceutical Science

Background:

• Digestive enzymes, such as trypsin, are crucial for nutrient absorption.
• Catechins, polyphenolic compounds found in tea, are known for their various health benefits, including potential enzyme inhibitory effects.

Purpose of the Study:

• To elucidate the inhibitory mechanism of catechins on trypsin.
• To analyze the structure-activity relationship of different catechins and their binding interactions with trypsin.

Main Methods:

• Integration of molecular docking, molecular dynamics simulations, and binding free energy calculations.
• Analysis of trypsin-catechin complexes, focusing on binding site interactions and conformational changes.

Main Results:

• Catechins bind to the conserved S1 pocket of trypsin, involving residues Asp189 (hydrogen bonding) and Gln192, Trp215, Gly216 (hydrophobic interactions).
• Binding affinity is influenced by hydroxyl/aromatic groups, stereoisomer structure, and orientation; EGCG exhibits the highest affinity, with 2R-3R EGCG being the most potent stereoisomer.
• Synergic conformational changes between trypsin residues and catechins were observed.

Conclusions:

• The study provides a detailed understanding of catechin-trypsin interactions at a molecular level.
• Findings support the rational design of polyphenol-based functional foods and nutraceuticals for digestive health.