atomic-resolution simulations predict a transition state for vesicle fusion defined by contact of a few lipid tails原子水平模拟预测过渡态一些脂质囊泡融合定义为接触反面.pdfVIP

Atomic-Resolution Simulations Predict a Transition State for Vesicle Fusion Defined by Contact of a Few Lipid Tails 1,2 2 1 Peter M. Kasson , Erik Lindahl , Vijay S. Pande * 1 Department of Chemistry, Stanford University, Stanford, California, United States of America, 2 Center for Biomembrane Research, Stockholm University, Stockholm, Sweden Abstract Membrane fusion is essential to both cellular vesicle trafficking and infection by enveloped viruses. While the fusion protein assemblies that catalyze fusion are readily identifiable, the specific activities of the proteins involved and nature of the membrane changes they induce remain unknown. Here, we use many atomic-resolution simulations of vesicle fusion to examine the molecular mechanisms for fusion in detail. We employ committor analysis for these million-atom vesicle fusion simulations to identify a transition state for fusion stalk formation. In our simulations, this transition state occurs when the bulk properties of each lipid bilayer remain in a lamellar state but a few hydrophobic tails bulge into the hydrophilic interface layer and make contact to nucleate a stalk. Additional simulations of influenza fusion peptides in lipid bilayers show that the peptides promote similar local protrusion of lipid tails. Comparing these two sets of simulations, we obtain a common set of structural changes between the transition state for stalk formation and the local environment of peptides known to catalyze fusion. Our results thus suggest that the specific molecular properties of individual lipids are highly important to vesicle fusion and yield an explicit structural model that could help explain the mechanism of catalysis by fusion proteins. Citation: Kasson PM, Lindahl E, Pande VS (2010) At