Gromacs Wizard Protein-Ligand MD preparation error

Patricio

Hello everyone,

I am trying to run a MD simulation of my protein-ligand complex. Given the situation with the incorrectly parametrized Gromos forcefields, I've been trying to run the simulation using Chramm36. I parametrized my ligand using the CGenFF website, and downloaded the Gromacs-converted files. These files include the following:

a copy of the charmm36.ff, with the files LIG.rtp and LIG_ffbonded.itp files within the forcefield directory;
LIG.pdb;
and LIG.top.

When trying to prepare the system, I get the following error from the Gromacs Wizard:
Fatal error:There were 19 missing atoms in molecule Other_chain_B, if you want to use thisincomplete topology anyhow, use the option -missing

With the actual Gromacs Error being:
Making bonds...
atom H26 is missing in residue GK2 1 in the pdb file
You might need to add atom H26 to the hydrogen database of building block GK2 in the file GK2.hdb (see the manual)
atom H27 is missing in residue GK2 1 in the pdb file...

I understand this is an issue of a missing file from CGenFF, given that there is no GK2.hdb provided in the charmm36.ff directory, but how should I go about solving this?

Thanks for your help.

DmitriyMarin

Hi @Patricio ,

Did the ligand structure that you submitted to CGenFF have all the necessary hydrogens?

For now, unfortunately, we don't yet have a GROMACS Wizard tutorial dedicated to the protein-ligand complex simulation with ligands parametrized using CGenFF. You can try to follow the corresponding steps from Justin Lemkul's Protein-ligand complex tutorial to obtain the ligand structure file and .itp file. You can add hydrogens in SAMSON, but the ligand needs to have charges and aromatic rings specified (it depends on the input file format).
Then you can combine the protein with the ligand structure directly in SAMSON. If needed, you can use Move editors to place the ligand, or the AutoDock Vina Extended to dock the ligand into a pocket. After that, you can follow the GROMACS Wizard tutorial with providing the generated .itp file and force field.

If you'd like, you can send us (via contact@samson-connect.net) an archive of your system (excluding the protein, if desired) to test and identify the issue.