CAJ | 학술논문

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。
내피소ET-1(Endothelin-1)여기수체ETA(Endothelin-A)화ETB(Endothelin-B)적상호작용공제혈관긴장도，유지혈압，여심혈관질병관계밀절。ET-1여혈관내피적ETB결합개도혈관서장，이여혈관평활기적ETA화ETB결합칙인기혈관수축。ET-1지유재존재정상혈류적체내실험재표현출명현적서장활성，차기결구구유유성，고추측혈류적전절응력가능공제료타적구상，진이조공타여ETB적결합。문장이용류동분자동역학계산궤모의방법，연구료균균류중질심수약속적내피소ET-1적구상。실험결과관찰도해분자적최기단왕안기단고근，정개분자변득긴주。저개발현대연구ET-1여ETB적상호작용화설계기우ET-1적심혈관약물장회유일정적지도의의。
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 lfow is present, we speculate that the shear stress of the blood lfow may control the conformation of ET-1 through its structural lfexibility, 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 ET-1 gets closer to the N-terminal in the simulation, resulting in a compact structure. This ifnding may provide guidance for the study on the interaction between ET-1 and ETB and the design of ET-1-based cardiovascular drugs.