| Summary: | 碩士 === 國立中央大學 === 化學學系 === 101 === Membrane fusion plays a key role in intracellular trafficking, neurotransmitter release, and viral infection. The molecular mechanism as well as energy landscape is not well understood. We have employed all-atom molecular dynamics simulations to study the entire fusion process of two hydrated 1-palmitoyl-2-oleoyl-sn-3-phosphoethanolamine (POPE) micelles induced by Ca2+ in a spontaneous fashion. This simulation system mimics the small contact zone between two large vesicles at which fusion may be initiated. Simulations reveal the Ca2+ is capable to catalyze the fusion of POPE micelles, whereas similar simulation with longer simulation time performed with Na+ does not observe the occurrence of fusion or even close contact of two micelles. We characterized the underlying molecular mechanism of fusion in terms of free energy landscape. The fusion is induced by the formation of inter-micelle Ca2+-lipid cluster. A prestalk state with solvent-exposed lipid tails involving in the inter-micelle Ca2+-lipid cluster has a higher free energy than the following stalk and hemifused-like states. In turn, the formation of the prestalk state is the rate-limiting step of fusion. A dewetting transition occurring in between the formation of prestalk and stalk states is observed. The formation of stalk state is determined by the dewetting transition. Our study indicates, for high hydration, the dewetting transition is the critical step in the stalk formation.
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