DOI: 10.5061/dryad.ns1rn8pw6
title: All-atom molecular dynamics simulations of synaptic vesicle fusion I: a glimpse at the primed Synaptotagmin-SNARE-complexin complex

description: Synaptic vesicles are primed into a state that is ready for fast
 neurotransmitter release upon Ca2+-binding to Syt1. This state likely
 includes trans-SNARE complexes between the vesicle and plasma membranes
 that are bound to Syt1 and complexins. However, the nature of this state
 and the steps leading to membrane fusion are unclear, in part because of
 the difficulty of studying this dynamic process experimentally. To shed
 light into these questions, we performed all-atom molecular dynamics
 simulations of systems containing trans-SNARE complexes between two flat
 bilayers or a vesicle and a flat bilayer with or without fragments of Syt1
 and/or complexin-1. Our results need to be interpreted with caution
 because of the limited simulation times and the absence of key components,
 but suggest mechanistic features that may control release and help
 visualize potential states of the primed Syt1-SNARE-complexin-1 complex.
 In particular, the simulations suggest that SNAREs alone induce formation
 of extended membrane-membrane contact interfaces that may fuse slowly, and
 that the primed state contains macromolecular assemblies of trans-SNARE
 complexes bound to the Syt1 C2B domain and complexin-1 in a spring-loaded
 configuration that prevents premature membrane merger and formation of
 extended interfaces but keeps the system ready for fast fusion upon
 Ca2+ influx.
description: After energy minimization, all systems were heated to 310 K over
 the course of a 1 ns MD simulation in the NVT ensemble and equilibrated
 for 1 ns in the NPT ensemble using isotropic Parrinello-Rahman pressure
 coupling. NPT production MD simulations were performed for the times
 indicated in Table 1 for each system using 2 fs steps, isotropic
 Parrinello-Rahman pressure coupling and a 1.1 nm cutoff for non-bonding
 interactions. All simulations were performed at 310 K except one
 simulation with the qscff system, which was performed at 325 K after a 310
 K simulation. Nose-Hoover temperature coupling was used separately for
 three groups: i) protein atoms plus Ca<sup>2+</sup> ions if
 present; ii) lipid atoms; and ii) water and KCL. Periodic boundary
 conditions were imposed with Particle Mesh Ewald (PME) summation for
 long-range electrostatics.
description: These data sets contain files associated with all-atom molecular
 dynamics simulations of the neurotransmitter release machinery between two
 flat bilayers or between a flat bilayer and a vesicle. Each directory
 corresponds to one simulation as described in the reference associated
 with this deposition and summarized in Table 1 of that reference. The
 simulations were performed with gromacs. Please refer to the gromacs
 manual (https://zenodo.org/record/6451567#.YoPaOJPMLOc) for more details. For each simulation, filenames have a common beginning (e.g. prsg for the simulation in the prsg directory) followed by a few letters that indicate the nature or order of the simulation: nvt for temperature equilibration runs; par for pressure equilibration runs and mdx for production simulations, where x is a number that denotes the order of a particular run within the chain of concatenated simulations. The filename extensions follow the common gromacs nomenclature. Here is a list of the types of files included in the deposition. Filenamea.sh or Filenameb.sh: text files with the SLURM instructions to run the simulation. These files show which files were used to run the particular simulation. Filename.top: topology file that includes calls to the force field and to other topology files and/or restraint files Filename.itp: topology or restraint file Filename.ndx: index file Filename.mdp: file containing the molecular dynamics parameters Filename.log: log file for the simulation Filename.gro: file with the coordinates and velocities at the end of the simulation Filename.cpt: checkpoint file containing the final coordinates and velocities with high precision to continue the simulation Filaname.edr: energy file Filenamecenterfit.pdb: selected frames that have been aligned with the initial configuration and converted to PDB format. In addition, each simulation directory contains force field, restraint and/or topology directories. The filename.xtc trajectory files that contain coordinates and velocities of frames saved during the simulations are not included because of their large size, which would render the deposition very expensive. These files are available from Josep Rizo upon reasonable request. This is the contact information: Name: Josep Rizo Institution: Department of Biophysics, UT Southwestern Medical Center Dallas Address: 6001 Forest Park Road, Dallas, TX 75390-8816 Email: Jose.Rizo-Rey@UTSouhtwestern.edu