食品与发酵工业2024，Vol.50Issue(11)：85-94,中插4-中插6,13.DOI:10.13995/j.cnki.11-1802/ts.036354
基于分子模拟技术的不同聚合度多酚与氧化三甲胺脱甲基酶的相互作用机制研究
Interaction mechanism between polyphenols with different degree of polymerization and trimethylamine-N-oxide demethylase based on molecular simulation study
摘要
Abstract
Endogenous formaldehyde is a common factor that affects the quality and safety of seafood.Trimethylamine N-oxide dem-ethylase(TMAOase)has been demonstrated to play a significant role in the formation of endogenous formaldehyde.Therefore,the forma-tion of endogenous formaldehyde in seafood can be effectively controlled by inhibiting the activity of TMAOase.The results of previous studies have shown that plant polyphenols can significantly inhibit the activity of TMAOase,while researchers mainly focused on the non-covalent interactions between polyphenols and TMAOase basing on inhibition kinetics and spectroscopic analysis.However,few teams at-tempted to elucidate their key binding sites and structure-activity relationships by molecular simulation techniques.Hence,the present study aims to investigate the interaction between polyphenols with different degrees of polymerization and TMAOase using molecular doc-king and molecular dynamics simulation studies.Also,the binding stability of the complexes and effects of polyphenols on the structure of TMAOase were analyzed.The data of molecular docking studies showed that four polyphenols with different degrees of polymerization were able to form complexes with TMAOase,which were mainly combined by hydrophobic interactions and hydrogen bonds.The binding capaci-ty of procyanidin B2 with TMAOase was the strongest,which could bind with TMAOase by hydrophobic residues(His-89,Phe-169,Gly-195,Gly-198,Gly-243,Phe-244)and hydrogen bonding sites(Thr-199 and Asn-438).The molecular dynamics simulation study indica-ted four polyphenols increased the surface hydrophobicity of TMAOase,while the number of intramolecular hydrogen bonds greatly de-creased.Nevertheless,no significant change in the secondary structure of enzyme was observed.The inhibitory effect of procyanidin B2 on TMAOase was non-competitive and the stability of complexes were the highest.In addition,the van der Waals force also played a role in the formation of the complexes.In a word,the interaction mechanism between polyphenols and TMAOase was explored at a molecular lev-el,which might provide a new idea for screening of TMAOase inhibitors in the future.关键词
氧化三甲胺脱甲基酶(TMAOase)/多酚/相互作用机制/分子对接/分子动力学Key words
trimethylamine N-oxide demethylase(TMAOase)/polyphenol/interaction mechanism/molecular docking/molecular dynam-ics引用本文复制引用
曾祥权,曹瑞,余美宏,赵劲灵,程洁仪,李健..基于分子模拟技术的不同聚合度多酚与氧化三甲胺脱甲基酶的相互作用机制研究[J].食品与发酵工业,2024,50(11):85-94,中插4-中插6,13.基金项目
国家重点研发计划项目(2022YFF1101500) （2022YFF1101500）
北京工商大学食品科学与工程"双一流"学科建设培育项目团队建设项目(BTBUYX-TD202203) （BTBUYX-TD202203）
北京市教委科技项目一般项目(KM202310011009) （KM202310011009）
