物理化学学报 >> 2014, Vol. 30 >> Issue (10): 1947-1956.doi: 10.3866/PKU.WHXB201408271

生物物理化学 上一篇    下一篇

甲基多巴透过POPC磷脂双层膜过程的分子动力学模拟

卞富永1,2, 张继伟1, 王丹1, 徐四川1   

  1. 1. 云南大学化学科学与工程学院, 自然资源药物化学教育部重点实验室, 昆明 650091;
    2. 楚雄医药高等专科学校, 云南楚雄 675005
  • 收稿日期:2014-05-13 修回日期:2014-08-25 发布日期:2014-09-30
  • 通讯作者: 徐四川 E-mail:sichuan@ynu.edu.cn
  • 基金资助:

    国家自然科学基金(21163024)和云南省教育厅科学研究基金(2013Y529)资助

Molecular Dynamics Simulation of the Permeation of Methyldopa through POPC Phospholipid Bilayer Membrane

BIAN Fu-Yong1,2, ZHANG Ji-Wei1, WANG Dan1, XU Si-Chuan1   

  1. 1. Key Laboratory of Education Ministry for Medicinal Chemistry of Natural Resource, College of Chemical Science and Technology, Yunnan University, Kunming 650091, P. R. China;
    2. Chuxiong Medical College, Chuxiong 675005, Yunnan Province, P. R. China
  • Received:2014-05-13 Revised:2014-08-25 Published:2014-09-30
  • Contact: XU Si-Chuan E-mail:sichuan@ynu.edu.cn
  • Supported by:

    The project was supported by the National Natural Science Foundation of China (21163024) and Education Science Foundation of Yunnan Province, China (2013Y529).

摘要:

采用分子动力学模拟研究甲基多巴分子透过磷脂双层膜的动力学机制. 研究所采用的磷脂双层膜是一种卵磷脂脂质分子双层膜,即1-棕榈酰-2-油酰-卵磷脂(POPC)双层膜,分子动力学模拟基于Gromacs程序. 通过分子动力学模拟获得甲基多巴透过POPC双层膜的自由能垒是99.9 kJ·mol-1(310 K),显示甲基多巴分子可以透过细胞生物膜. 模拟获得甲基多巴在POPC双层膜中间层扩散运动的自由能垒是16.9-27.7 kJ·mol-1(310 K),证明甲基多巴分子在细胞膜中间层容易扩散. 研究工作加深了对甲基多巴治疗高血压病机制的理解,促进研发治疗高血压病的新药物.

关键词: 甲基多巴, 高血压, 细胞膜, POPC, 分子模拟, 分子动力学

Abstract:

The molecular dynamics mechanism for methyldopa permeation through the phospholipid bilayer membrane has been studied by molecular dynamics simulation. The phospholipid bilayer membrane used in the work was one type of lecithin phospholipid bilayer membrane called the 1-palmitoyl-2-oleoyl-glycero-3- phosphate dylcholine (POPC) bilayer membrane, and the molecular dynamics simulation was performed with the Gromacs program. The free energy barrier for methyldopa to permeate through the POPC bilayer membrane was 99.9 kJ·mol-1 (310 K) from the molecular dynamics simulation, suggesting that methyldopa is capable of permeating through the cell membrane. The free energy barrier for methyldopa to diffuse through the POPC bilayer membrane was 16.9-27.7 kJ·mol-1 (310 K), which indicates that it is easy for methyldopa to diffuse through the cell membrane. Therefore, the results of the free energy barrier give information of the mechanism for methyldopa to metabolize in the human body. Furthermore, the results help to understand the mechanism for methyldopa in treating hypertension disease, and have significance for developing new drugs to control hypertension.

Key words: Methyldopa, Hypertension, Cell membrane, POPC, Molecular simulation, Molecular dynamics

MSC2000: 

  • O641