Membrane fusion is a crucial mechanism in a wide variety of important events in cell biology from viral infection to exocytosis. However, despite many efforts and much progress, cell–cell fusion has remained elusive to our understanding. Along the life of the fusion pore, large conformational changes take place from the initial lipid bilayer bending, passing through the hemifusion intermediates, and ending with the formation of the first nascent fusion pore. In this sense, computer simulations are an ideal technique for describing such complex lipid remodeling at the molecular level. In this work, we studied the role played by the muscle-specific membrane protein Myomerger during the formation of the fusion pore. We have conducted μs length atomistic and coarse-grained molecular dynamics, together with free-energy calculations using ad hoc collective variables. Our results show that Myomerger favors the hemifusion diaphragm–stalk transition, reduces the nucleation–expansion energy difference, and promotes the formation of nonenlarging fusion pores.

中文翻译：

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Myomerger 诱导膜半融合并调节融合孔扩张

膜融合是细胞生物学中从病毒感染到胞吐作用等各种重要事件中的关键机制。然而，尽管做出了许多努力并取得了很大进展，但细胞与细胞的融合仍然难以为我们所理解。在融合孔的生命周期中，从最初的脂质双层弯曲，经过半融合中间体，并以第一个新生融合孔的形成结束，发生了巨大的构象变化。从这个意义上说，计算机模拟是在分子水平上描述这种复杂脂质重塑的理想技术。在这项工作中，我们研究了肌肉特异性膜蛋白 Myomerger 在融合孔形成过程中所发挥的作用。我们进行了μs长度的原子和粗粒度分子动力学，以及使用临时集体变量的自由能计算。我们的结果表明，Myomerger 有利于半融合隔膜-柄转变，减少成核-膨胀能量差，并促进非扩大融合孔的形成。