Ligand topology (CGenFF) with high charge penalties

User discussions
1

GROMACS version: 2022.2
GROMACS modification: Yes

I am trying to use MD to evaluate a docking pose obtained with autodock vina. But I am having issues generating the ligand topology using the CGenFF server. I followed all the same steps shown in the tutorial (Protein-Ligand complex). I converted the ligand to mol2, and fixed the bonds’ order with the script “sort_mol2_bonds.pl” provided on the GROMACS page. The ligand_fix.mol2 file seems correct when opened in ChimeraX and contains all hydrogens. However, the .str file generated contains high charge penalties and the pdb resultant does not show the proper structure anymore. What is the possible reason and how could I fix this issue? Thanks!

2

Is your residue name 4 characters or shorter in the .str file (RESI XXXX)? If not, you’ll get a misformatted PDB file.

As for the high penalties, check the CGenFF papers (particularly the original 2010 JCC paper) for how to validate and refine a topology. It will require QM calculations and is most easily done in the CHARMM software (for some things, there are no equivalent functions in GROMACS).