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

• Published in: PloS one 2015-05, Vol.10 (5), p.e0125848-e0125848
• Main Authors: Cui, Fengchao, Yang, Kecheng, Li, Yunqi
• Format: Article
• Language: English
• Subjects: Affinity; Alzheimer's disease; Alzheimers disease; Amino Acids - chemistry; Analysis; Artificial rubber; Binding; Biological activity; Bonding; Bonding strength; Cancer; Catechin; Catechin - chemistry; Catechin - metabolism; Chemical properties; Chemistry; Digestive enzymes; Drug resistance; Electrocardiography; Epicatechin; Epigallocatechin gallate; Epigallocatechin-3-gallate; Food; Free energy; Free radicals; Hydrogen; Hydrogen bonding; Hydrophobicity; Investigations; Laboratories; Mechanics; Molecular chains; Molecular Conformation; Molecular docking; Molecular Docking Simulation; Molecular dynamics; Molecular Dynamics Simulation; Monte Carlo simulation; Protein Binding; Proteins; Residues; Simulation; Stereoisomers; Structure-Activity Relationship; Tea - chemistry; Trypsin; Trypsin - chemistry; Trypsin - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0125848

To explore the inhibitory mechanism of catechins for digestive enzymes, we investigated the binding mode of catechins to a typical digestive enzyme-trypsin and analyzed the structure-activity relationship of catechins, using an integration of molecular docking, molecular dynamics simulation and binding free energy calculation. We found that catechins with different structures bound to a conservative pocket S1 of trypsin, which is comprised of residues 189-195, 214-220 and 225-228. In the trypsin-catechin complexes, Asp189 by forming strong hydrogen bonding, and Gln192, Trp215 and Gly216 through hydrophobic interactions, all significantly contribute to the binding of catechins. The number and the position of hydroxyl and aromatic groups, the structure of stereoisomers, and the orientation of catechins in the binding pocket S1 of trypsin all affect the binding affinity. The binding affinity is in the order of Epigallocatechin gallate (EGCG) > Epicatechin gallate (ECG) > Epicatechin (EC) > Epigallocatechin (EGC), and 2R-3R EGCG shows the strongest binding affinity out of other stereoisomers. Meanwhile, the synergic conformational changes of residues and catechins were also analyzed. These findings will be helpful in understanding the knowledge of interactions between catechins and trypsin and referable for the design of novel polyphenol based functional food and nutriceutical formulas.