Insights into Membrane Fusion from Molecular Dynamics Simulations of SNARE Proteins

Exocytosis involves the transport of molecules stored within lipid vesicles across the vesicle and cell boundaries. The final step of this process requires fusion of the vesicles with the cell membrane mediated by SNARE proteins. SNARE function requires specific protein properties possibly in order to actively pull and subsequently hold together two membranes. Previous work have demonstrated the stability of the SNARE soluble complex with the help of atomistic m olecular dynamics simulations [1]. We now want to investigate the molecular mechanisms that could drive fusion. We focus especially on the interaction of the SNARE complex with the membrane. 1 2 3 S During equilibration, the membranes move away from each other to compensate for expansion and pressure buildup, while the transmembrane domains (TMDs) remain firmly inserted within the bilayers. The core complex holds the TMDs which maintain some lipids in place leading to a deformation of the leaflets . From this starting structure , three simulations were performed for 100ns with the CHARMM 36 forcefield