食品与发酵工业 >

2024 , Vol. 50 >Issue 10: 290 - 297

DOI: https://doi.org/10.13995/j.cnki.11-1802/ts.036602

分析与检测

三种描述符对食源性血管紧张素转化酶抑制二肽定量构效关系研究

  • 郭星晨 ,
  • 李华鑫 ,
  • 张钰璇 ,
  • 马金璞 ,
  • 杨具田 ,
  • 李贞子 ,
  • 高丹丹
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  • 1(西北民族大学,生物医学研究中心中国-马来西亚国家联合实验室,甘肃 兰州,730030)
    2(西北民族大学 生命科学与工程学院,甘肃 兰州,730124)
第一作者:硕士研究生(高丹丹教授为通信作者,E-mail:gaodan0322@163.com)

收稿日期: 2023-06-28

  修回日期: 2023-08-01

  网络出版日期: 2024-06-11

基金资助

兰州市城关区科技计划项目(2022JSCX0011);西北民族大学中央高校基本科研业务费资金资助项目(31920230153);国家自然科学基金项目(31960461);西北民族大学校地合作项目配套基金资助项目(BELTY201901,HLRP-KY—20210902);甘肃省研究生“创新之星”项目(2023CXZX-207)

收起

Quantitative structure-activity relationship of angiotensin converting enzyme inhibitor dipeptides based on three descriptors

  • GUO Xingchen ,
  • LI Huaxin ,
  • ZHANG Yuxuan ,
  • MA Jinpu ,
  • YANG Jutian ,
  • LI Zhenzi ,
  • GAO Dandan
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  • 1(China-Malaysia National Joint Laboratory, Biomedical Research Center, Northwest Minzu University, Lanzhou 730030, China)
    2(College of Life Science and Engineering, Northwest Minzu University, Lanzhou 730124, China)

Received date: 2023-06-28

  Revised date: 2023-08-01

  Online published: 2024-06-11

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摘要

为探究血管紧张素转化酶(angiotensin converting enzyme, ACE)抑制肽结构与功能的关系,阐明食源性ACE抑制肽作用机理,该文收集最近报道的血管紧张素转化酶抑制二肽的氨基酸序列及其IC50值,用Z-scales、VHSE和SVHEHS三种氨基酸描述符对ACE抑制二肽的结构进行表征,以氨基酸的疏水性质、立体性质以及电性性质参数作为自变量,ACE抑制二肽的lg(IC50)作为因变量,建立ACE抑制二肽的定量构效模型。结果显示基于Z-scales描述符建立的二肽定量构效模型R2为0.847 7,Q2为0.828 4,模型预测二肽Phe-Phe有较高的ACE抑制活性,预测IC50为1.049 9 μmol/L,实测IC50为(1.041 4±0.004 1) μmol/L,预测值与实测值误差为0.008 5 μmol/L。基于VHSE描述符构建的模型R2为0.856 8,Q2为0.805 2,模型预测二肽Asp-Trp有较高的ACE抑制能力,预测IC50为1.216 0 μmol/L,实测IC50为(1.110 0±0.005 3) μmol/L,误差为0.106 0 μmol/L。基于SVHEHS描述符构建的定量构效模型R2为0.858 1,Q2为0.745 3 μmol/L,模型预测二肽Ala-Trp有较高的ACE抑制活性,预测IC50为1.032 3 μmol/L,实测IC50为(1.129 0±0.008 2) μmol/L,误差为0.096 7 μmol/L。3种氨基酸描述符均能较为合适地对ACE抑制二肽进行定量构分析。通过模型分析发现ACE抑制肽C端氨基酸残基疏水特性和立体特征与其活性关系更为密切,其氨基酸残基的疏水特征和立体特征越强,ACE抑制肽的活性越强。通过3种ACE抑制二肽与ACE蛋白(2X8 J)进行分子对接发现,3种ACE抑制肽均可与ACE蛋白进行结合。表明通过偏最小二乘法对Z-scales、VHSE、SVHEHS三种描述符对ACE抑制二肽构建定量构效关系模型是可行的。这将对ACE抑制肽的检测、预测和筛选具有积极的意义。

关键词： 血管紧张素转化酶; 肽; 定量构效; 氨基酸描述符; 偏最小二乘法; 半抑制浓度

本文引用格式

郭星晨 , 李华鑫 , 张钰璇 , 马金璞 , 杨具田 , 李贞子 , 高丹丹 . 三种描述符对食源性血管紧张素转化酶抑制二肽定量构效关系研究[J]. 食品与发酵工业, 2024 , 50(10) : 290 -297 . DOI: 10.13995/j.cnki.11-1802/ts.036602

Abstract

This study aimed to investigate the relationship between structure and function of ACE(angiotensin converting enzyme, ACE) inhibitory peptide and to elucidate the mechanism of action of food-derived ACE inhibitory peptide.The amino acid sequences of recently reported ACE inhibitory dipeptides and their IC50 values were collected, and the structures of ACE inhibitory dipeptides were characterized using three amino acid descriptors, Z-scales, VHSE, and SVHEHS, with the hydrophobic properties, steric properties, and electrical properties of amino acids. The hydrophobic properties, steric properties, and electrical properties of the amino acids were used as independent variables and the lg(IC50) of the ACE inhibitory dipeptide was used as the dependent variable to establish the quantitative conformational model of the ACE inhibitory dipeptide.Results showed that the R2 and Q2 of quantitative structure-activity relationship model constructed based on Z-scales descriptor were 0.847 7 and 0.828 4, and the model predicted that the dipeptide sequence with higher activity of ACE inhibitory peptide was Phe-Phe, and the predicted IC50 was 1.049 9 μmol/L, and the measured IC50 was (1.041 4±0.004 1) μmol/L.The error between the predicted and measured values was 0.008 5 μmol/L.That the R2 and Q2 of QSAR model constructed based on VHSE descriptor were 0.856 8 and 0.805 2, and the model predicted a high ACE inhibition capacity for Asp-Trp, with a predicted IC50 of 1.216 0 μmol/L and a measured value of (1.110 0±0.005 3) μmol/L, with an error of 0.106 0 μmol/L.That the R2 and Q2 of model constructed based on SVHEHS descriptor were 0.858 1 μmol/L and 0.745 3 μmol/L.and the model predicts a high ACE inhibitory activity of dipeptide Ala-Trp with a predicted IC50 of 1.032 3 μmol/L and a measured value of (1.129 0±0.008 2) μmol/L, with an error of 0.096 7 μmol/L.All three amino acid descriptors were suitable for the quantitative conformational analysis of ACE inhibitory dipeptide.The model analysis revealed that the hydrophobic characteristics and steric characteristics of the C-terminal amino acid residues of the ACE inhibitory peptide were more closely related to its activity, and the stronger the hydrophobic characteristics and steric characteristics of its amino acid residues, the stronger the activity of the ACE inhibitory peptide.The molecular docking of the three ACE inhibitory dipeptides with ACE protein (2X8 J) revealed that all three ACE inhibitory peptides could bind to ACE protein.It showed that it was feasible to construct QSAR models for the three descriptors of ACE inhibitory dipeptides by partial least squares method for Z-scales, VHSE, and SVHEHS.This will have positive implications for the detection, prediction and screening of ACE inhibitory peptides.

Key words： angiotensin converting enzyme; peptides; quantitative structure-activity relationship; amino acid structure descriptor; partial Least-Squares Regression; semi-inhibitory concentration

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