Protocol for Simulations of PEGylated Proteins with Martini 3 (Tutorial Files)

This repository comprises all input files required to run our tutorial on simulating PEGylated proteins.

Abstract

Enhancement of proteins by PEGylation is an active area of research. However, the interactions between polymer and protein are far from fully understood. To gain a better insight into these interactions or even make predictions, molecular dynamics (MD) simulations can be applied to study specific protein-polymer systems at molecular level detail. Here we present instructions on how to simulate PEGylated proteins using the latest iteration of the Martini coarse-grained (CG) force-field. CG MD simulations offer near atomistic information and at the same time allow to study complex biological systems over longer time and length scales than fully atomistic-level simulations.

Usage Notes

• run the commands within the downloaded directory
• if you run on MacOS or Windows you need to adjust the shell commands
• the protocol is unfortunetly out of date with the current version of polyply.

PEGylating Proteins with polyply > v1.2

In order to PEGylate the protein as in the chapter example, we first need to generate the complete residue graph of the PEGylated protein. This is done by the following command:

polyply gen_seq -f molecule_0.itp -from_file protein:molecule_0\
                           -from_string linker:1:1:MEE-1.0 polymer:50:1:PEO-1.0 end:1:1:OHend-1.0\
                           -seq protein linker polymer end\
                           -connects 0:1:0-0 1:2:0-0 2:3:49-0\
                           -o sequence.json -name test\
                           -label 0:"from_itp":"molecule_0-1."

See an in depth explanation of this command here. However, it should work to simply use it for any protein that is generated with martinize2 provided the itp file has the name molecule_0.itp. Next we generate the itp file of the combined molecule in one go:

polyply gen_itp -f molecule_0.itp MEE.itp combined_links.ff PEO.martini.3b.itp .OH_end.itp -seqf sequence.json -o lysoPEG.itp -name lysoPEG

If you experience any problems, have questions, or need advice on your molecule simply create a new discussion thread here or post under the old one.

Citation

@incollection{grunewaldprotocol,
  title={Protocol for Simulations of PEGylated Proteins with Martini 3},
  author={Gr{\"u}newald, Fabian and Kroon, Peter C and Souza, Paulo CT and Marrink, Siewert J},
  booktitle={Structural Genomics},
  pages={315--335},
  publisher={Springer}
}