Interactions between neuronal fusion proteins explored by molecular dynamics

In this report, we present features of the neuronal SNARE complex determined by atomistic molecular dynamics simulations. The results are robust for three models, varying force fields (AMBER and GROMOS) and solvent environment (explicit and implicit). An excellent agreement with experimental findings is observed. The SNARE core complex behaves like a stiff rod, with limited conformational dynamics. An accurate picture of the interactions within the complex emerges with a characteristic pattern of atomic contacts, hydrogen bonds, and salt bridges reinforcing the underlying layer structure. This supports the metaphor of a molecular Velcro strip that has been used by others to describe the neuronal fusion complex. No evidence for directionality in the formation of these interactions was found. Electrostatics largely dominates all interactions, with an acidic surface patch structuring the hydration layers surrounding the complex. The interactions within the four-helix bundle are asymmetric, with the synaptobrevin R-SNARE notably exhibiting an increased rigidity with respect to the three Q-SNARE helices. The interaction patterns we observe provide a new tool for interpreting the impact of mutations on the complex.