Modified Glutamine residue (polyQ)

User discussions
1

GROMACS version:
GROMACS modification: Yesglu
Hello!

I’m trying to investigate a polyglutamilation effect in tubulins ( https://en.wikipedia.org/wiki/Polyglutamylation or https://www.nature.com/articles/s41594-020-0462-0#Sec25 ), which seems to be a slightly tricky task.

First of all I’ve to generate a non-terminal glutamine which is a part of the chain (for example, chain A), but its terminal gamma carboxyl group forms a peptide bond with glutmaine tag (in attachment). I think, that I can build such strange amino acid, forming three peptide bonds at once, with R.E.D.III or something else. Thus, it should look like a simple in-chain glutamine with a replaced gamma-carboxyl oxygen by amide group of the connected glutamine. This is already difficult manipulation, but the number of the added glutamines can vary.

Another way to generate a new topology based on GAFF force field parameters library. As we can replace carboxyl group with amide group of asparagine and calculate the difference in charges with gaussian/gamess. Is it real or not?

Then I thought about the possibility of binding together of two separate chains (like cys-cys) - namely, one chain contains a modified glutamine residue, and all substituted in gamma position glutamines belong to another chain. Is it possible or not? Of course charge distribution should be correctly tuned up to reflect natural behaviour of the construction.

Is it possible or not? Do You have any suggestions?

Thank You!

2

Hello!
Does anybody found any ways to solve the problem? Maybe this topic is outside the view of the users and admins?
Thank You!

3

Hi Rufus,

Sorry for getting back so late, sometimes questions get overlooked.

For your issue, I would guess that it’s indeed a number of challenging tasks you pose. I don’t have the experience to help you out on the parametrization. Once you have the parameters, you can include a newly parametrized amino acid in two ways :

  • modify the force-field files in share/gromacs/top (.rtp, .hdb, etc) - much effort, but then you can reuse the residue in all cases and you can use all the gromacs tools to generate your topolgy - find more information here: http://manual.gromacs.org/current/how-to/topology.html

  • modify the topology files to include your residue, by adding the residue manually. If you have a peek into .top files you will see all the different interactions defined, some explanation can be found here

and in the manual here

and here

4

well, thank You very much!