食品科学2024，Vol.45Issue(13)：38-48,11.DOI:10.7506/spkx1002-6630-20230613-106
基于氨基酸描述符对血管紧张素转化酶抑制五肽定量构效关系分析
Quantitative Structure-Activity Relationship Analysis of Angiotensin-Converting Enzyme Inhibitory Pentapeptides Based on Amino Acid Descriptors
摘要
Abstract
This study aimed to investigate the structure-function relationship of angiotensin-converting enzyme(ACE)inhibitory peptides and to elucidate the action mechanism of food-derived ACE inhibitory peptides.Based on the amino acid sequences of recently reported ACE inhibitory pentapeptides and their half-maximal inhibitory concentration(IC50)values,a library of ACE inhibitory pentapeptides was generated and the structures of the ACE inhibitory pentapeptides were characterized using three amino acid descriptors,Z-scales,VHSE and SVHEHS.A partial least square(PLS)model for describing the quantitative structure-activity relationship(QSAR)of the ACE inhibitory peptides with the hydrophobic properties,steric properties,and electrical properties of amino acids as the independent variables and the lg IC50 of the ACE inhibitory pentapeptides as the dependent variable was established using Matlab software.The results showed that the R2 and Q2 of the QSAR model based on Z-scales descriptor were 0.641 1 and 0.536 9,respectively,and Gln-Arg-Pro-Asn-Met showed higher ACE inhibitory activity as predicted by this model.The predicted and measured IC50 were 0.051 7 and(0.040 0±0.008 3)μmol/L,respectively,and the error between them was 0.011 7 μmol/L.The R2 and Q2 of the QSAR model based on VHSE descriptor were 0.763 6 and 0.508 1,respectively,and Leu-Arg-Ala-Phe-Gln exhibited better ACE inhibitory activity as predicted by this model.The predicted and measured IC50 were 0.043 8 and(0.027 3±0.005 3)μmol/L,respectively,and the error between them was 0.016 5 μmol/L.The R2 and Q2 of the QSAR model based on SVHEHS descriptor were 0.840 5 and 0.400 5,respectively,and Leu-Arg-Ala-Phe-Gln displayed better ACE inhibitory activity as predicted by this model.The predicted and measured IC50 were 0.005 5 and(0.031 2±0.004 2)μmol/L,and the error between them was 0.025 7 μmol/L.Among the three QSAR models,the one based on SVHEHS descriptor had the strongest fitting capability but weak predictive capacity,while the models based on Z-scales and VHSE descriptors could allow good QSAR analysis of the pentapeptides.Our modeling analysis showed that the activity of the ACE inhibitory peptides was negatively correlated with the hydrophobic characteristics of amino acids and positively correlated with the steric characteristics of amino acids.Molecular docking of three ACE inhibitory peptides to ACE protein(2X8J)showed that all the ACE inhibitory peptides could bind to ACE protein.This study provides a new tool for developing ACE inhibitory peptides and a theoretical basis for the development and application of food-derived ACE inhibitory peptides.关键词
血管紧张素转化酶/肽/偏最小二乘/定量构效关系/氨基酸描述符Key words
angiotensin-converting enzyme/peptides/partial least squares/quantitative structure-activity relationship/amino acid structure descriptors分类
轻工业引用本文复制引用
郭星晨,李玉豪,马金璞,张钰璇,李华鑫,杨具田,樊佩如,高丹丹..基于氨基酸描述符对血管紧张素转化酶抑制五肽定量构效关系分析[J].食品科学,2024,45(13):38-48,11.基金项目
西北民族大学中央高校基本科研业务费资金资助项目(31920230153) （31920230153）
兰州市城关区科技计划项目(2022JSCX0011) （2022JSCX0011）
甘肃省教育厅青年博士基金项目(2023QB-001) （2023QB-001）
甘肃省科技厅技术创新引导计划-科技专员专项(23CXGA0078) （23CXGA0078）
甘肃省科技厅技术创新引导计划-科技型中小企业创新基金项目(23CXGP0002) （23CXGP0002）
甘肃省重点人才项目 （）
西北民族大学校地合作项目配套基金资助项目(BELTY201901 （）
HLRP-KY-20210902) （）
国家自然科学基金地区科学基金项目(31960461) （31960461）
西北民族大学校级大学生创新创业训练计划项目(X202310742278) （X202310742278）
甘肃省高等教育教学培育项目(2022GSJXCGI09) （2022GSJXCGI09）
西北民族大学校级创新创业教育示范专业项目(2022XJCXCYSFZY01) （2022XJCXCYSFZY01）
