The free-energy landscape of interaction between a medium-sized peptide, endothelin 1 (ET1), and its receptor, human endothelin type B receptor (hETB), was computed using multidimensional virtual-system coupled molecular dynamics, which controls the system's motions by introducing multiple reaction coordinates. The hETB embedded in lipid bilayer was immersed in explicit solvent. All molecules were expressed as all-atom models. The resultant free-energy landscape had five ranges with decreasing ET1-hETB distance: completely dissociative, outside-gate, gate, binding pocket, and genuine-bound ranges. In the completely dissociative range, no ET1-hETB interaction appeared. In the outside-gate range, an ET1-hETB attractive interaction was the fly-casting mechanism. In the gate range, the ET1 orientational variety decreased rapidly. In the binding pocket range, ET1 was in a narrow pathway with a steep free-energy slope. In the genuine-bound range, ET1 was in a stable free-energy basin. A G-protein-coupled receptor (GPCR) might capture its ligand from a distant place.

中文翻译：

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内皮素 1 和人内皮素 B 型受体之间分子相互作用的自由能景观：飞投机制。

使用多维虚拟系统耦合分子动力学计算中型肽内皮素 1 (ET1) 与其受体人内皮素 B 型受体 (hETB) 之间相互作用的自由能景观，该系统通过以下方式控制系统的运动：引入多个反应坐标。将嵌入脂质双层的 hETB 浸入显性溶剂中。所有分子均表示为全原子模型。由此产生的自由能景观具有五个随着 ET1-hETB 距离减小的范围：完全解离、外门、门、结合口袋和真正结合的范围。在完全解离范围内，没有出现ET1-hETB相互作用。在门外范围内，ET1-hETB 吸引相互作用是飞投机制。在门范围内，ET1取向变化迅速下降。在结合口袋范围内，ET1 处于具有陡峭自由能斜率的狭窄路径中。在真实束缚范围内，ET1 处于稳定的自由能盆地。G 蛋白偶联受体 (GPCR) 可能会从远处捕获其配体。