分子动力学模拟法研究丹参酮II_A与胆固醇酯转运蛋白的相互作用模式  

Molecular dynamics simulation of interaction mode between tanshinone II_A and cholesteryl ester transfer protein

作　　者：张洁[1,2] 谭初兵[2] 徐为人[1,2] 李晓博[1] 汤立达[2] 

机构地区：[1]天津医科大学基础医学院,天津300070 [2]天津药物研究院天津市新药设计与发现重点实验室,天津300193

出　　处：《中草药》2013年第13期1793-1800,共8页Chinese Traditional and Herbal Drugs

基　　金：国家重大新药创制专项(2011ZX09401-009,2010ZX09401-307-1-1);天津科技支撑项目(10ZCKFSHO1300)

摘　　要：目的通过研究丹参酮IIA与胆固醇酯转运蛋白(CETP)的相互作用,探索其对CETP的影响模式。方法基于晶体结构构建丹参酮IIA与CETP多种形式的复合结构,并以此为起始结构进行分子动力学模拟,模拟软件为Gromacs 4.0,力场Gromos 96 53a6,温度300 K,模拟时间20 ns,记录轨迹,分析CETP整体形状和局部结构变化,考察丹参酮IIA与CETP的相互作用能量。结果磷酯酰胆碱出口区和空腔都装满后CETP结构比较刚性,单装空腔CETP结构容易变化。对应于CETP框架结构的形态变化,在与不同配体复合形式下CETP两侧的出口区和磷酯酰胆碱出口区以及空腔差异较大,丹参酮IIA与CETP相互作用较强的情况出现在2个磷酯酰胆碱出口位置和空腔左侧位置。结论 CETP是一个结构比较容易变化的载体蛋白,受装载配体结构和数量的影响容易发生相应变化,丹参酮IIA可能具有通过与磷酯酰胆碱或胆固醇酯共同作用影响CETP的形态,从而抑制其转运的能力。Objective To investigate the interaction between tanshinone ⅡA （TS ⅡA） and cholesteryl ester transfer protein （CETP）, and to explore the ways of impact on CETP. Methods The various structures of TS IIA and CETP were built based on the crystal structure and then performed molecular dynamics （MD）. The simulation software is Gromacs 4.0 with force field of Gromos 96 53a6. The temperature is 300 K and the simulation time is 20 ns. All trajectories were recorded to analyze the changes of overall shape and local structures of CETP, and the interaction energy between TS ⅡA and CETP. Results When the phosphatidyl choline zones of CETP were full, the structure was rigid. When only the cavity was loaded, CETP was easy to change. The out area of two side, phosphatidyl choline area and cavity change greatly corresponded to the frame changes of CETP. Stronger interaction between TS ⅡA and CETP occured in the two phosphatidyl choline area and the left side of cavity. Conclusion CETP is a carrier protein with easily changed structure which changes according to the differences in the number and structures of loading ligands. TS ⅡA might affect the morphology of the CETP and then inhibit its transportation ability under the help ofphosphatidyl choline or cholesterol ester.

关 键 词：丹参酮IIA 胆固醇酯转运蛋白 相互作用 转运 分子动力学 

分 类 号：R965.1[医药卫生—药理学] R977.15[医药卫生—药学]