摘要
本研究收集近些年报道的血管紧张素转化酶(angiotensin converting enzyme,ACE)抑制五肽的氨基酸序列及抑制活性(半抑制浓度(half maximal inhibitory concentration,IC_(50))),建立ACE抑制五肽肽库,并将其氨基酸残基用Z-scales、VHSE和SVHEHS氨基酸描述符分别进行表述,以氨基酸残基的疏水性、立体性以及电性参数作为自变量,ACE抑制五肽的lg IC_(50)作为因变量,利用Matlab软件用偏最小二乘法建立ACE抑制肽定量构效关系(quantitative structure-activity relationship,QSAR)模型,结果发现基于Z-scales描述符构建的ACE抑制五肽QSAR模型R2为0.6411,Q^(2)为0.5369,模型预测五肽Gln-Arg-Pro-Asn-Met具有较高的ACE抑制活性,预测IC_(50)为0.0517μmol/L,实测IC_(50)为(0.0400±0.0083)μmol/L,预测值与实测值误差为0.0117μmol/L;基于VHSE描述符构建的QSAR模型R2为0.7636,Q^(2)为0.5081,模型预测五肽Leu-Arg-Ala-Phe-Gln具有较高的ACE抑制活性,预测IC_(50)为0.0438μmol/L,实测值为(0.0273±0.0053)μmol/L,误差为0.0165μmol/L;基于SVHEHS描述符构建的QSAR模型R2为0.8405,Q^(2)为0.4005μmol/L,模型预测五肽Tyr-Phe-Pro-Phe-Gln具有较高的ACE抑制活性,预测值为0.0055μmol/L,实测值为(0.0312±0.0042)μmol/L,误差为0.0257μmol/L。3种建模方法对比发现,基于SVHEHS描述符构建的模型拟合能力最强,但是其预测能力较弱,而Z-scales和VHSE描述符所建模型能很好地对五肽进行QSAR分析,通过模型分析发现ACE抑制肽活性与其氨基酸的疏水特征呈负相关,与立体特征呈正相关。将3种ACE抑制肽与ACE蛋白(2X8J)进行分子对接,结果表明3种ACE抑制肽均可与ACE蛋白进行结合。本研究可为开发ACE抑制肽药物提供新手段,为开发和利用食源性ACE抑制肽提供理论基础。
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(IC_(50))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 IC_(50)of the ACE inhibitory pentapeptides as the dependent variable was established using Matlab software.The results showed that the R2 and Q^(2)of the QSAR model based on Z-scales descriptor were 0.6411 and 0.5369,respectively,and Gln-Arg-Pro-Asn-Met showed higher ACE inhibitory activity as predicted by this model.The predicted and measured IC_(50)were 0.0517 and(0.0400±0.0083)μmol/L,respectively,and the error between them was 0.0117μmol/L.The R2 and Q^(2)of the QSAR model based on VHSE descriptor were 0.7636 and 0.5081,respectively,and Leu-Arg-Ala-Phe-Gln exhibited better ACE inhibitory activity as predicted by this model.The predicted and measured IC_(50)were 0.0438 and(0.0273±0.0053)μmol/L,respectively,and the error between them was 0.0165μmol/L.The R2 and Q^(2)of the QSAR model based on SVHEHS descriptor were 0.8405 and 0.4005,respectively,and Leu-Arg-Ala-Phe-Gln displayed better ACE inhibitory activity as predicted by this model.The predicted and measured IC_(50)were 0.0055 and(0.0312±0.0042)μmol/L,and the error between them was 0.0257μmol/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 V
作者
郭星晨
李玉豪
马金璞
张钰璇
李华鑫
杨具田
樊佩如
高丹丹
GUO Xingchen;LI Yuhao;MA Jinpu;ZHANG Yuxuan;LI Huaxin;YANG Jutian;FAN Peiru;GAO Dandan(China-Malaysia National Joint Laboratory,Biomedical Research Center,Northwest Minzu University,Lanzhou 730030,China;Life Science and Engineering College of Northwest Minzu University,Lanzhou 730124,China;College of Chemistry,Sichuan University,Chengdu 610207,China)
出处
《食品科学》
EI
CAS
CSCD
北大核心
2024年第13期38-48,共11页
Food Science
基金
西北民族大学中央高校基本科研业务费资金资助项目(31920230153)
兰州市城关区科技计划项目(2022JSCX0011)
甘肃省教育厅青年博士基金项目(2023QB-001)
甘肃省科技厅技术创新引导计划-科技专员专项(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)
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)
西北民族大学校级大学生创新创业训练计划项目(X202310742278)
甘肃省高等教育教学培育项目(2022GSJXCGI09)
西北民族大学校级创新创业教育示范专业项目(2022XJCXCYSFZY01)。
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
angiotensin-converting enzyme
peptides
partial least squares
quantitative structure-activity relationship
amino acid structure descriptors
