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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。
Endothelin-1 (Endothelin-1) and its receptor ETA (Endothelin-A) and ETB (Endothelin-B) interaction control of vascular tone, maintain blood pressure, and cardiovascular disease are closely related. ET-1 mediates vasodilation by binding to ETB of the vascular endothelium, whereas vasoconstriction is induced by binding of ET-1 to ETB of vascular smooth muscle. ET-1 only shows obvious diastolic activity in in vivo experiments with normal blood flow, and its structure is flexible. Therefore, it is speculated that the shear stress of blood flow may control its conformation and regulate its binding with ETB. In this paper, the conformation of endothelin ET-1, which is constrained by the centroid in a uniform flow, was studied by means of flow cytokinetic computer simulation. The experimental results observed that the carboxyl terminal of the molecule is close to the amino terminal, and the whole molecule becomes compact. This finding will be instructive in studying the interaction between ET-1 and ETB and in designing cardiovascular drugs based on ET-1.