The use of non-viral vectors for in vivo gene therapy could drastically increase safety, whilst reducing the cost of preparing the vectors. A promising approach to non-viral vectors makes use of DNA/cationic liposome complexes (lipoplexes) to deliver the genetic material. Here we use coarse-grained molecular dynamics simulations to investigate the molecular mechanism underlying efficient DNA transfer from lipoplexes. Our computational fusion experiments of lipoplexes with endosomal membrane models show two distinct modes of transfection: parallel and perpendicular. In the parallel fusion pathway, DNA aligns with the membrane surface, showing very quick release of genetic material shortly after the initial fusion pore is formed. The perpendicular pathway also leads to transfection, but release is slower. We further show that the composition and size of the lipoplex, as well as the lipid composition of the endosomal membrane, have a significant impact on fusion efficiency in our models.

This dataset contains all initial set-up files as well as PDBs and GRO files. Trajectories have been left out but are available on requests within reason (this was too much to upload here ~1TB). There is a readme which explains the internal folder system.

Included filetypes:
.ndx
.gro
.xtc (not included but available on request)
.tpr
.mdp

The basic set up of all simuations is as follows:
1) initial; not always completely used and often copied for ease of scripting,
therefore names could deviate from what was really used in specific cases. In
general the initial folder is the /scratch folder for generating the intial
configurations. It also contains a toppar folder which contains the used .itp
files. However, the .tpr file in de specific simulation folder is the actual
input file used, the same holds for the mdout.mdp wich contains the actual
settings used for the run. However, it has been included for it sometimes
contains useful pre-structures.
2) em; basic initial energy minimization
3) eq; basic numerical equilibration
4) md; initial testing of md settings, this hardly ever contains the real simulation data, this is more pre-run to see if there are any issues.
5) md_peregrine/md_cartesius; the actual production runs performed on the
corresponding super computer.

I you have any question feel free to send an email to:
bartbruininks@gmail.com and I will try to help you out.

Cheers and all the best,

Bart M H Bruininks
University of Groningen (2020)