Molecular Dynamics Simulations of the SNARE Complex Interacting with Synaptotagmin, Complexin, and Lipid Bilayers.

Molecular dynamics (MD) simulations enable in silico investigation of the dynamic behavior of proteins and protein complexes. Here, we describe MD simulations of the SNARE bundle forming the complex with the neuronal proteins Synaptotagmin-1 (Syt1) and Complexin (Cpx). Syt1 is the synaptic vesicle (SV) protein that serves as the neuronal calcium sensor and triggers synaptic fusion upon calcium binding, and this process is promoted and accelerated by Cpx. The fusion depends on the Syt1 interactions with the SNARE-Cpx complex and with the lipid bilayer of the presynaptic membrane (PM). The MD simulations of the PM-Syt1-SNARE-Cpx-SV molecular system described here enabled us to investigate how this protein-lipid complex promotes the merging of SV and PM, triggering synaptic fusion.