文献类型：期刊文献

英文题名：Investigation on the characteristics and mechanisms of ACE inhibitory peptides by a thorough analysis of all 8000 tripeptides via binding free energy calculation

作者：Chen, Ruiyao[1];Miao, Yulu[2];Hao, Xuan[2];Gao, Bei[1];Ma, Mingzhe[2];Zhang, John Z. H.[2,3,4];Wang, Rui[5,6];Li, Sha[5,6];He, Xiao[2,3];Zhang, Lujia[2,3]

机构：[1]East China Univ Sci & Technol, Sch Biotechnol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[2]East China Normal Univ, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, Sch Chem & Mol Engn, Shanghai, Peoples R China;[3]NYU Shanghai, NYU ECNU Ctr Computat Chem, Shanghai, Peoples R China;[4]NYU, Dept Chem, New York, NY USA;[5]Nanjing Tech Univ, Coll Food Sci & Light Ind, Nanjing, Peoples R China;[6]Nanjing Tech Univ, State Key Lab Mat Oriented Chem Engn, Nanjing, Peoples R China

年份：2021

卷号：9

期号：6

起止页码：2943

外文期刊名：FOOD SCIENCE & NUTRITION

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000646286000001)】；

基金：National Key R&D Program of China, Grant/Award Number: 2020YFA0908400; National Natural Science Foundation of China, Grant/Award Number: 31571786 and U1805235; Innovation Program of Shanghai Municipal Education Commission, Grant/Award Number: 201701070005E00020; Shanghai Municipal Natural Science Foundation, Grant/Award Number: 18ZR1412600; Open Research Fund of State Key Laboratory of Materials--Oriented Chemical Engineering, Grant/Award Number: KL19-12; NYU-ECNU Center for Computational Chemistry at NYU Shanghai

语种：英文

外文关键词：ACE inhibitor; in silico experiment; inhibitory mechanism; tripeptides

摘要：Food-derived angiotensin I-converting enzyme (ACE) inhibitory peptides represent a potential source of new antihypertensive. However, their characteristics and binding mechanisms were not well understood. In this study, novel energy calculation and experimentation were combined to elucidate the characteristics and mechanisms of ACE inhibitory tripeptides. ACE inhibitory activity of all 8,000 tripeptides was investigated by in silico experiments. IC50 values of the five top-rated tripeptides ranged from 5.86 to 21.84 mu M. Five hundred top-ranked tripeptides were chosen for detailed structure-activity analysis, and a significant preference for aromatic amino acids at both C- and N-terminus was found. By binding free energy analysis of nine representative tripeptides via MM/GBSA, electrostatic energy was found to be the leading energy that contributed to the binding of ACE with its high affinity tripeptides. Besides, S355, V380, and V518, three residues positioned around the classical binding pockets of ACE, also played a key role in ACE's binding. Therefore, for tripeptides, their binding pockets in ACE were redefined. In conclusion, the characteristics of ACE inhibitory peptides were more deeply illustrated by the thorough analysis of all tripeptides. The energy analysis allows a better understanding of the binding mechanisms of ACE inhibitory peptides, which could be used to redesign the ACE inhibitors for stronger inhibitory activity.