Fusion proteins can play a versatile and involved role during all stages of the fusion reaction. Their roles go far beyond forcing the opposing membranes into close proximity to drive stalk formation and fusion. Molecular simulations have played a central role in providing a molecular understanding of how fusion proteins actively overcome the free energy barriers of the fusion reaction up to the expansion of the fusion pore. Unexpectedly, molecular simulations have revealed a preference of the biological fusion reaction to proceed through asymmetric pathways resulting in the formation of, e.g., a stalk-hole complex, rim-pore, or vertex pore. Force-field based molecular simulations are now able to directly resolve the minimum free-energy path in protein-mediated fusion as well as quantifying the free energies of formed reaction intermediates. Ongoing developments in Graphics Processing Units (GPUs), free energy calculations, and coarse-grained force-fields will soon gain additional insights into the diverse roles of fusion proteins.

融合蛋白在融合反应的各个阶段都可以发挥多种作用。它们的作用远远超出了迫使相对的膜靠近以驱动茎的形成和融合。分子模拟在提供关于融合蛋白如何主动克服融合反应的自由能障碍直至融合孔扩张的分子理解方面发挥了核心作用。出乎意料的是，分子模拟揭示了生物融合反应偏好通过不对称途径进行，导致形成例如茎孔复合体、边缘孔或顶孔。基于力场的分子模拟现在能够直接解析蛋白质介导的融合中的最小自由能路径，并量化形成的反应中间体的自由能。图形处理单元 (GPU)、自由能计算和粗粒度力场的持续发展很快将获得对融合蛋白不同作用的更多见解。