The Role of Ionizable Lipids in SARS-CoV-2 Vaccines As Revealed by Molecular Dynamics Simulations: From Membrane Structure to Interaction with mRNA Fragments

Paloncýová, M., Čechová, P., Šrejber M., Kuhrova P. and Otyepka, M. “The Role of Ionizable Lipids in SARS-CoV-2 Vaccines As Revealed by Molecular Dynamics Simulations: From Membrane Structure to Interaction with mRNA Fragments”

> Parameters > AMBER                                                 : AMBER parameters for lipid molecules (*.prepi) and input file for production run (*.in)

> Parameters > GROMACS                                               : GROMACS parameters for lipid molecules (*.itp)

> Trajectories > SL1_in_water                                        : topologies (*.prmtop), starting structures (*.pdb) and striped trajectories (*.trr) for SL1 in water (last 200 ns used for analysis; striped to the total of 1000 frames)

> Trajectories > Lipid systems > Bilayers                            : systems created as pre-assambled bilayers

> Trajectories > Lipid systems > Bilayers > Pure                     : topologies (*.prmtop), starting structures (*.pdb) and striped trajectories (*.trr) for single lipid component systems (last 200 ns used for analysis; striped to the total of 1000 frames)

> Trajectories > Lipid systems > Bilayers > Mixtures                 : topologies (*.prmtop), starting structures (*.pdb) and striped trajectories (*.trr) for lipid mixtures systems (last 200 ns used for analysis; striped to the total of 1000 frames)

> Trajectories > Lipid systems > Self-assembly                       : self-assembly systems

> Trajectories > Lipid systems > Self-assembly > Individual lipids   : topologies (*.prmtop), starting structures (*.pdb) and striped trajectories (*.trr) for single lipid component systems and binary mixture of DSPC:CHL ()

> Trajectories > Lipid systems > Self-assembly > Mixtures            : topologies (*.prmtop), starting structures (*.pdb) and striped trajectories (*.trr) for lipid mixtures systems (last 200 ns used for analysis; striped to the total of 1000 frames)

> Trajectories > SL1_lipid_mixtures                                  : topologies (*.prmtop), starting structures (*.pdb) and striped trajectories (*.trr) of SL1 in lipid mixtures (last 200 ns used for analysis; striped to the total of 1000 frames)

> Analysis > Bilayer_analysis.sh                                     : analysis structural parameters from bilayer simulations

> Analysis > voro_surfaces_calculation.sh                            : runs trjvoronoi; generates interaction surfaces

> Analysis > surfaces_hist_better_graph_culling_table_with_RNA.py    : reads data generated by voro_surfaces_calculation.sh and exports average interaction surfaces per group

NOMENCLATURE:

SL1                     … Stem Loop 1

P                       … lipid mixture used in the Pfizer&BioNTech vaccine

M                       … lipid mixture used in the Moderna vaccine

xL                      … x stands for number of lipids

xWpL                    … x stands for the level of hydration (# of Waters per Lipid)

LIPID_0                 … (zero) after lipid/mixture denotes neutral (uncharged, deprotonated) form of ionizable lipid

4CB                     … 4 Component Bilayer

in_water                … simulation in water (and ions) without lipids

NOTE: For mor details on simulation setup, please see original publications and Supporting Information.