Neuronal SNARE (Soluble N-ethylmaleimide sensitive factor protein receptor) protein complexes are responsible for mediating the fusion of vesicles with the cellular membrane, a key step in neurotransmission. Many details of this process are known but a quantitative mechanistic description is still lacking.
Here, we study the process of zipping and unzipping of neuronal SNARE by means of coarse-grained molecular dynamics simulations. We show how a simple structure-based model is able to reproduce the results of single-molecule pulling experiments, characterizing a biologically relevant partially unzipped intermediate.
We observe that, in agreement with previous experimental results, the unzipped region in this intermediate starts at the central ionic layer of the bundle. This ionic layer is a highly conserved region containing only charged and polar side chains, located halfway down the length of the complex. We analyze the role of electrostatic interactions in stabilizing the intermediate, and the effect of possible mutations on the transition rates.
We also investigate possible different pathways followed during the unzipping process and analyze their dependence on the coarse-grained model employed.
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