Is it allowed to use Charmm36 ff on protein and GAFF on ligand?

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1

GROMACS version: 2021.7
GROMACS modification: Yes/No
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I want to use Charmm36 ff on protein and GAFF on ligand, as one of my ligands has Se and Charmm GUI or CGenFF are not able to generate the .itp file for that ligand. What should I do?

2

This is from a different context, but still valid: “If you are trying to mix two force fields, then you are asking for trouble.” (Common errors when using GROMACS - GROMACS 2024.3 documentation)

While it can be possible to make it work with a lot of effort, all your results will be questionable at best (probably outright wrong). You should make sure that the force fields you are using are compatible. Charmm36 and GAFF (Amber FF) are not compatible.

3

Thank You for the advice.

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When CGenFF fails to parametrize a molecule, as in this case, how can one generate parameters that are compatible with CHARMM36m?

For instance, formaldehyde is not supported by CGenFF, while acetaldehyde is parametrized without issue.

5

There are a few alternatives, as I see it:

  • Have you tried both http://charmm-gui.org/ and https://cgenff.com? (I don’t know if they generate exactly the same parameters and cover exactly the same chemical space.)
  • You could see if other CGenFF parametrisation methods work. Have a look at MATCH: Brooks Lab - Match - University of Michigan.
  • You could parametrise the molecule yourself according to the CGenFF instructions. I’m quite sure you’ll need Gaussian for this.
  • You could switch the protein force field to Amber and use GAFF for the ligand. If there are other components, such as lipids, they would of course also have to switch to an Amber compatible force field.
  • You could contact the CGenFF developers to see if you can help them (and whether they would like such help) developing parameters and automatic parametrisation for such a ligand.
  • You could wait and hope that CGenFF will be able to parametrise your ligand in the future.