Kasson Peter M, Zomorodian Afra, Park Sanghyun, Singhal Nina, Guibas Leonidas J, Pande Vijay S
Medical Scientist Training Program, Stanford University, Stanford, CA 94305, USA.
Bioinformatics. 2007 Jul 15;23(14):1753-9. doi: 10.1093/bioinformatics/btm250. Epub 2007 May 8.
Membrane fusion constitutes a key stage in cellular processes such as synaptic neurotransmission and infection by enveloped viruses. Current experimental assays for fusion have thus far been unable to resolve early fusion events in fine structural detail. We have previously used molecular dynamics simulations to develop mechanistic models of fusion by small lipid vesicles. Here, we introduce a novel structural measurement of vesicle topology and fusion geometry: persistent voids.
Persistent voids calculations enable systematic measurement of structural changes in vesicle fusion by assessing fusion stalk widths. They also constitute a generally applicable technique for assessing lipid topological change. We use persistent voids to compute dynamic relationships between hemifusion neck widening and formation of a full fusion pore in our simulation data. We predict that a tightly coordinated process of hemifusion neck expansion and pore formation is responsible for the rapid vesicle fusion mechanism, while isolated enlargement of the hemifusion diaphragm leads to the formation of a metastable hemifused intermediate. These findings suggest that rapid fusion between small vesicles proceeds via a small hemifusion diaphragm rather than a fully expanded one.
Software available upon request pending public release.
Supplementary data are available on Bioinformatics online.
膜融合是细胞过程中的关键阶段，如突触神经传递和包膜病毒感染。目前用于融合的实验检测方法迄今无法在精细结构细节上解析早期融合事件。我们之前使用分子动力学模拟来建立小脂质囊泡融合的机制模型。在此，我们引入了一种囊泡拓扑结构和融合几何结构的新型结构测量方法：持续空洞。
持续空洞计算通过评估融合柄宽度能够系统地测量囊泡融合中的结构变化。它们还构成了一种评估脂质拓扑变化的通用技术。我们使用持续空洞来计算模拟数据中半融合颈加宽与完全融合孔形成之间的动态关系。我们预测，半融合颈扩张和孔形成的紧密协调过程是快速囊泡融合机制的原因，而半融合隔膜的孤立扩大导致亚稳态半融合中间体的形成。这些发现表明，小囊泡之间的快速融合是通过小的半融合隔膜而非完全扩张的隔膜进行的。
软件可应要求提供，待公开发布。
补充数据可在《生物信息学》在线获取。
