内皮素-1在均匀流中构象改变的分子动力学模拟  

Molecular Dynamics Simulation of Endothelin-1 Conformational Changes within Uniform Flow

作　　者：黄庆生[1] 肖天霞[1] 张键[1] 魏彦杰[1] 

机构地区：[1]中国科学院深圳先进技术研究院,深圳518055

出　　处：《集成技术》2014年第2期17-26,共10页Journal of Integration Technology

基　　金：国家自然科学基金项目(31100850);国家自然科学基金项目(11204342);深圳杰出青年基金项目(SW201110059);深圳市科技创新委员会项目(JCYJ20120615140912201);深圳市孔雀计划项目(KQCX20130628112914299)

摘　　要：内皮素ET-1(Endothelin-1)与其受体ETA(Endothelin-A)和ETB(Endothelin-B)的相互作用控制血管紧张度,维持血压,与心血管疾病关系密切。ET-1与血管内皮的ETB结合介导血管舒张,而与血管平滑肌的ETA和ETB结合则引起血管收缩。ET-1只有在存在正常血流的体内实验才表现出明显的舒张活性,且其结构具有柔性,故推测血流的剪切应力可能控制了它的构象,进而调控它与ETB的结合。文章利用流动分子动力学计算机模拟方法,研究了均匀流中质心受约束的内皮素ET-1的构象。实验结果观察到该分子的羧基端往氨基端靠近,整个分子变得紧凑。这个发现对研究ET-1与ETB的相互作用和设计基于ET-1的心血管药物将会有一定的指导意义。Interactions of ET-1 （Endothelin-1） with its receptors ETA （Endothelin-A） and ETB （Endothelin-B） regulate the vascular tone, maintain the blood pressure, and are closely related to cardiovascular diseases. Binding of ET-1 with ETB in the vascular endothelium induces vasodilation, while binding with ETA and ETB in vascular smooth muscle results in vasoconstriction. Because ET-1 only induces vasodilation in vivo when the blood flow is present, we speculate that the shear stress of the blood flow may control the conformation of ET-1 through its structural flexibility, thus regulate its binding with ETB. By flow molecular dynamics simulation, the conformational changes of ET-1 in uniform flow were studied with its center of mass constrained. It is found that the C-terminal of ETol gets closer to the N-terminal in the simulation, resulting in a compact structure. This finding may provide guidance for the study on the interaction between ET-1 and ETB and the design of ET-1-based cardiovascular drugs.

关 键 词：内皮素-1 内皮素B受体 均匀流 分子动力学模拟 

分 类 号：R312[医药卫生—基础医学]