食品科学

• 基础研究 •    下一篇

血管紧张素转化酶抑制二肽抑制ACE作用的柔性分子对接

管 骁1,刘 静2,*,苏淅娜1,韩 飞3,王文高4,5,申瑞玲6,李景军7,廖丽丽8   

  1. 1.上海理工大学医疗器械与食品学院,上海 200093;2.上海海事大学信息工程学院,上海 200135;
    3.国家粮食局科学研究院,北京 100037;4.上海良友(集团)有限公司,上海 200333;5.上海市粮食科学研究所,
    上海 200333;6.郑州轻工业学院食品与生物工程学院,河南 郑州 450002;7.江苏长寿集团股份有限公司,
    江苏 如皋 226500;8.桂林西麦食品集团,广西 桂林 541004
  • 出版日期:2015-03-15 发布日期:2015-03-17

Flexible Molecular Docking of Interaction between Angiotensin Ⅰ-Converting Enzyme (ACE) Inhibitory Dipeptides and ACE

GUAN Xiao1, LIU Jing2,*, SU Xina1, HAN Fei3, WANG Wengao4,5, SHEN Ruiling6, LI Jingjun7, LIAO Lili8   

  1. 1. School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093,
    China; 2. College of Information Engineering, Shanghai Maritime University, Shanghai 200135, China;
    3. Academy of State Administration of Grain, Beijing 100037, China; 4. Shanghai Liangyou (Group) Co. Ltd., Shanghai 200333,
    China; 5. Shanghai Grain Science Research Institute, Shanghai 200333, China; 6. School of Food and Bioengineering,
    Zhengzhou University of Light Industry, Zhengzhou 450002, China; 7. Jiangsu Changshou (Group) Co. Ltd., Rugao 226500, China;
    8. Guilin Ximai Food Company, Guilin 541004, China
  • Online:2015-03-15 Published:2015-03-17

摘要:

食源性血管紧张素转化酶(angiotensin Ⅰ-converting enzyme,ACE)抑制肽可有效抑制生物体内ACE活性,进而起到降压疗效,且作用温和,无副作用,是高血压治疗的理想药物,但其分子作用机制一直未有明确解释。本实验选取4 个代表性食源ACE抑制二肽(Gly—Phe、Gly—Tyr、Val—Phe、Ile—Tyr)为研究对象,采用柔性分子对接的方法研究它们与ACE的相互作用模型与分子机理。分子对接结果表明:氢键、亲水、疏水、静电等作用力同时对二肽与ACE的结合有贡献,但以氢键作用为主;ACE分子中Ala354、Glu384、Arg522等氨基酸残基为二肽与其结合的重要活性位点;ACE抑制二肽中氮端氨基对其抑制活性影响显著。通过以上分子机理研究可为指导开发强活性ACE抑制肽提供理论指导。

关键词: 血管紧张素转化酶, 抑制二肽, 分子对接, 分子机理

Abstract:

AngiotensinⅠ-converting enzyme (ACE) inhibitory peptides are ideal anti-hypertension drugs because they
can inhibit ACE activity in vivo effectively, and have strong blood-reducing activity without side effects. However,
their molecular mechanism remains unclear so far. In this paper, four typical ACE inhibitory dipeptides including GF
(Gly-Phe), GY (Gly-Tyr), VF (Val-Phe) and IY (Ile-Tyr) were chosen as research targets, and their action modes and
molecular mechanisms on ACE were studied in detail by flexible molecular docking method. The results showed that
hydrogen bond, hydrophobic, hydrophilic and electrostatic interactions existed between peptides and ACE, in which hydrogen
bond interaction plays the dominant role. Moreover, Ala354, Glu384 and Arg522 in ACE were especially important binding site
with active peptides, and N-terminal amino groups were the key groups in dipeptides. This information will be helpful for the
molecule design of new ACE inhibitory peptides with strong activity.

Key words: angiotensin Ⅰ-converting enzyme, inhibitory dipeptides, molecular docking, molecular mechanism

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