Pdb2gmx fails: Residue 'MGP' not found in CHARMM36 force field

User discussions
, , ,
1

Hello everyone,

I am trying to set up a simulation for the eIF4E protein in complex with the 5’ cap analog, m⁷GTP, using the PDB entry 4TPW. In this PDB file, this molecule is assigned the residue name ‘MGP’.

My goal is to run a simulation using GROMACS with the CHARMM36 force field. However, pdb2gmx fails when processing the ligand.

System Details:

  • GROMACS Version: 2020.2

  • Force Field: CHARMM36 (Jul-2022 version, downloaded from the MacKerell lab website)

  • Operating System: macOS Sonoma

Command Used:

gmx pdb2gmx -f 4tpw_cleaned.pdb -o complex.gro -p topol.top -ignh

Error Message: The command terminates with the following fatal error:

Fatal error:
Residue 'MGP' not found in residue topology database

My Understanding: I understand this error occurs because the standard CHARMM36 force field does not include parameters for this non-standard molecule (MGP). I have confirmed that if I remove the MGP molecule from the PDB file, pdb2gmx processes the protein part without any issues.

My Question: I would be grateful for some guidance on the recommended workflow to parametrize the MGP ligand for use with CHARMM36 in GROMACS.

I am aware that I need to generate a topology (.itp file) and parameters for MGP. I have read about using the CGenFF server for similar tasks. Is the correct general procedure to:

  1. Isolate the MGP ligand into its own coordinate file.

  2. Submit it to the CGenFF server to obtain a stream (.str) file with its parameters.

  3. Use a conversion script (like cgenff_charmm2gmx.py) to convert the CGenFF output into a GROMACS-compatible format (.itp file and additions to ffnonbonded.itp).

Is this still the current best practice? If so, are there any updated tutorials or guides for this process? Any advice on how to correctly integrate the resulting files into my system topology would be greatly appreciated.

Thank you in advance for your help!

2

The residue you need is already in the CHARMM force field, although you will have to add it to the GROMACS port because it isn’t something we have converted. The residue is called 7MG in CHARMM and is in toppar/stream/na/toppar_all36_na_rna_modified.str. You can get this file from Alex MacKerell’s website. Simply create a new residue in the .rtp file by modifying the existing guanine nucleotide by updating the atom definitions and bonds.