Multiple Go models

Note

At time of writing, the -name flag of martinize2 necessary for this tutorial is not available in the version of vermouth installed directly via pip. Make sure that Vermouth has been installed using:

$ pip install git+https://github.com/marrink-lab/vermouth-martinize/

If you have a system containing several proteins, each of which has been coarse grained with their own Go model, then extra care needs to be taken during simulation and visualisation. The exact nature and behaviour of the Go model is outside the scope of this tool, but interested readers are referred to the excellent work of Korshunova et al. should they be interested in further details of pitfalls of multiple Go models in a single system.

Simulation set up

Martinizing two proteins

If multiple proteins are martinized with Go models and intended for the same simulation setup, then care must be taken in the preparation of input files. When the -go flag is used in Martinize2, two additional files are written if the Go model is generated successfully: go_atomtypes.itp and go_nbparams.itp.

For multiple go models, these should first be renamed to indicate which system they’re associated with (otherwise, running martinize2 twice in the same directory will overwrite the files made for the first protein):

# martinize the first protein
$ martinize2 -f prot0_clean.pdb -x prot0_cg.pdb -o prot0_topol.top -go prot0_contact_map.out -name prot0
$ mv go_nbparams.itp prot0_go_nbparams.itp
$ mv go_atomtypes.itp prot0_go_atomtypes.itp

# martinize the second protein
$ martinize2 -f prot1_clean.pdb -x prot1_cg.pdb -o prot1_topol.top -go prot1_contact_map.out -name prot1
$ mv go_atomtypes.itp prot1_go_atomtypes.itp
$ mv go_nbparams.itp prot1_go_nbparams.itp

Once the files are all generated, the ones relevant to the go model should be concatenated together:

# concatenate the files together
$ cat prot0_go_nbparams.itp prot1_go_nbparams.itp > go_nbparams.itp
$ cat prot0_go_atomtypes.itp prot1_go_atomtypes.itp > go_atomtypes.itp

Generating a structure file

After the proteins have been coarse-grained individually and the Go files treated accordingly, an initial simulation cell can be assembled using the program of choice. In the tutorial script, gmx insert-molecules is used twice over to insert several copies of each into a single simulation cell called vis.gro:

# make the box with multiple copies of each molecule using gromacs
$ gmx insert-molecules -ci prot0_cg.pdb -nmol 5 -box 20 20 20 -o newbox.gro
$ gmx insert-molecules -ci prot1_cg.pdb -nmol 3 -f newbox.gro  -o vis.gro
$ rm newbox.gro

Visualisation

Running MartiniGlass

With the input files treated appropriately, MartiniGlass can in fact be run as with any other system. In the case of the tutorial files, the following command will generate all the visualisation topologies from the input files as described above:

$ martiniglass -p topol.top -go -gf go_nbparams.itp -vf -f vis.gro

As usual, this can then be opened in vmd:

$ vmd vis.gro -e vis.vmd

In the case of the files found in the output folder of the tutorial, the VMD scene looks as the following:

Where the five copies of prot0 have been coloured in yellow, and the three copies of prot1 in distinct colours. In this case, the visualisation of the Go network has been particularly useful for prot1, because the large likely disordered loops generated by AlphaFold have been attached with Go bonds, which will almost certainly result in unphysical behaviour.