Coarse-grain simulations of the R-SNARE fusion protein in its membrane environment detect long-lived conformational sub-states.

Coarse-grain molecular dynamics are used to look at conformational and dynamic aspects of an R-SNARE peptide inserted in a lipid bilayer. This approach allows carrying out microsecond-scale simulations which bring to light long-lived conformational sub-states potentially interesting in the context of the membrane fusion mechanism mediated by the SNARE proteins. We show that these coarse-grain models are in agreement with most experimental data on the SNARE system, but differ in some details that may have a functional interest, most notably in the orientation of the soluble part of R-SNARE that does not appear to be spontaneously accessible for SNARE complex formation. We also compare rat and yeast sequences of R-SNARE and find some minor differences in their behavior.

Alpha,beta-D-CNA induced rigidity within oligonucleotides.

Introduction of alpha,beta-D-CNA featuring canonical values of the torsional angles alpha and beta within oligonucleotides leads to an overall stabilization and improved rigidity of the duplex DNA as demonstrated by UV experiments, circular dichroism and corroborated by molecular dynamics simulations.

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.