The conformational change associated with membrane fusion for Influenza A Hemagglutinin is investigated with a model based upon pre- and post-fusion structures of the HA2 component. We employ computational methods based on the potential energy landscape framework to obtain an initial path connecting these two end points, which provides the starting point for refinement of a kinetic transition network. Here we employ discrete path sampling, which provides access to the experimental time and length scales via geometry optimization techniques to identify local minima and the transition states that connect them. We then analyse the distinct phases of the predicted pathway in terms of structure and energetics, and compare with available experimental data and previous simulations. Our results provide the foundations for future work, which will address the effect of mutations, changes in pH, and incorporation of additional components, especially the HA1 chain and the fusion peptide.

使用基于HA2组分融合前后结构的模型研究了与A型流感血凝素膜融合相关的构象变化。我们使用基于势能态势框架的计算方法来获得连接这两个端点的初始路径，这为完善动力学过渡网络提供了起点。在这里，我们采用离散路径采样，通过几何优化技术提供对实验时间和长度比例的访问，以识别局部最小值和将其连接的过渡状态。然后，我们根据结构和能量学分析预测路径的不同阶段，并与可用的实验数据和先前的模拟进行比较。我们的结果为将来的工作奠定了基础，