Issues with Modified CHARMM-GUI Generated System


Using CharmmGUI, I created a membrane-protein-solvent system and ran simulations on it. Now, I need to run the same simulation but with an anionic non-standard ligand in the protein. This brings up several issues!

Firstly, the membrane involves TLCL, which, astonishingly, is not included in the Charmm36 port for GROMACS that I downloaded from MacKerell Lab. Therefore, running
mpirun gmx_mpi_openmp pdb2gmx -f step5_input.pdb -o step5_input.gro -ter
yields the error
Residue 'TLCL' not found in residue topology database.
What should I do? In the input files Charmm generated for the previous simulation, there’s a toppardirectory that includes several residues, including the mentioned TLCL2.itp.

Another question I have is how can I simply add K+ ions to neutralize the system?

Maybe I overthink this: the point is just I need to rerun the computations with the docked anionic ligand. Maybe there’s an option to do that otherwise?

Thanks in advance.

The problem with CHARMM-GUi is that if you change anything about the system, the topology and force field files it gives you are no longer valid. The CHARMM36 port is a faithful translation of the exact CHARMM36 force field, for which there is indeed no TLCL residue. It does have TLCL1 and TLCL2, for the two ionization states of the lipid. 5-character residue codes are incompatible with PDB format, so there’s no way to specify them. CHARMM-GUI is doing some translating behind the scenes to give you a working topology. If you change anything, you’re out of luck.

Rebuild the system in CHARMM-GUI, and let it rebuild everything with the CGenFF topology for the ligand.

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Dear Prof. @jalemkul ,

I am going to equilibrate a protein in POPE lipids generated in Charmm-gui, take the protein, dock small molecules into it and perform MD simulations for ligand-protein complexes for the molecules chosen according to the docking results.

Is there any automated method to insert the molecule into the pre-equilibrated system using Gromacs, without generating the system again with Charmm-gui?
(I hope even I can remove the water molecules overlapping with the ligand by hand.)

Then, can I separately generate and use the CGenFF topologies for the ligand, add to the system topology and perform the simulation?

Thank you!

You can provide a fully composed system to CHARMM-GUI and have it generate a topology, including parametrizing the ligand.