SAM co-factor with CHARMM force field for GROMACS silmualtion

User discussions
1

Hello All,

Following the GROMACS tutotial on Protein-ligand complex, I am trying to simulate a protein having SAM as one of its ligands using the CHARMM force field. All my attempts to get the topology file for SAM failed. I would like to know if anyone has succeeded in writing the topology (itp file for SAM with CHARMM FF) of this well-known ligand to help me do so as well.

Best,
Bourgeois

2

For CHARMM compatible topologies, I think your choices are CHARMM-GUI, https://cgenff.com/ or Brooks Lab - Match - University of Michigan (possibly via STaGE, GROMACS / STaGE · GitLab). Have you tried all these alternatives?

3

I have tried CHARMM-GUI and CGenFF but could not figure it out.

4

Hi Gabbi,

I would like to obtain CHARMM ff for SAM molecule but couldn’t achieve it via CHARMM-GUI, and CGENFF. Then I tried to form it manually by collecting info from toppar_prot and toppar_na, however I still don’t have the full bonded terms list. The reference (Senn et al., 2005, 127, 13643-13655) list newly generated terms but some are missing or I couldn’t find. Have you obtained the parameter file?

5

Hello Gulshah,

Getting the CHARMM force field for SAM can look tricky at first, but it’s actually more straightforward than it seems. SAM is already defined in charmm36-jul2022.ff.

If you’re simulating SAM together with a protein, I recommend the following steps:

  1. Prepare your PDB file

    • Clean your protein PDB so that it contains the protein plus the SAM ligand.

    • If your original PDB has other ligands besides SAM, extract them into separate PDB files and treat them individually. Keep only the protein and SAM together in the same file.

  2. Generate topology with GROMACS

    • Run:

      gmx pdb2gmx -f protein_SAM.pdb -o processed.gro -p topol.top -ff charmm36-jul2022

    • Alternatively, if you just want SAM by itself, you can run:

      gmx pdb2gmx -f SAM.pdb -o SAM.gro -p topol.top -ff charmm36-jul2022

  3. Check the output

    • For the combined system, you’ll usually get two .itp files:

      • topol_Protein_chain_A.itp (protein)

      • topol_Other_chain_A2.itp (SAM)

    • Both are automatically included in the topol.top file.

This way, you don’t need to manually collect bonded terms–everything is handled within CHARMM36.

Best regards,
Gabbi

6

Thank you very much Gabbi, it worked!