PDB HETATM

[Anonymous]

I am working on relaxing two PDB structures to do Protein Protein docking using Rosetta 3

The PDB structure is a single chain followed by a TER record and then a collection of HETATM for the ligand. The PDB has a three letter ligand term in the amino acid field and running relax.linuxgccrelease throws an error unrecognized aa VD3. I edited the PDB file and replaced with spaces and relax didn’t like that either.

What do I need to do to allow HETATM?

Do I need to move the TER record to after the last HETATM?

Thanks

Scooter Willis

[Anonymous]

I found a related post in the rosetta++ forum that appears I need to pull the ligand out of the PDB file as if I was doing a Protein-ligand docking. The ligand in my particular example is required for the protein to dock with a different protein which also requires a different ligand.

If I have two PDB files that I want to do Protein-Protein docking where each has a ligand what steps do I need to go through to make sure the ligands are considered in the overall best docking model for the lowest score.

[Anonymous]

If you want Rosetta to consider arbitrary ligands, you need to supply a ligand parameter file so that Rosetta understands what its atoms are and how they connect. This is true even if you want the ligand left alone. Check the ligand docking documentation for how to generate these parameter files (look for “molfile_to_params.py”.

https://www.rosettacommons.org/manuals/rosetta3_user_guide/app_ligand_docking.html

Including the parameter file will hopefully allow relax to handle the existence of the ligand.

That said, it’s possible that docking will still refuse to recognize your ligand (it won’t crash, but it might ignore it). If the ligand is not at your interface, you’ll be okay; if the ligands are at the interface this might or might not cause problems. I suspect that the docking code will try to dock the first two chains in the PDB together and ignore the other chains, I’m not sure.

If docking does cause problems, you’ll have to go into the docking code and tweak its foldtree a bit – this is not hard but it’s scary if you don’t know C++. Basically you’d need to ensure that the rigid-body jump between the two proteins was modified, but that the rigid-body transformations between ligands and their proteins was not.

If you want to do docking between ligands AND proteins, you’d be better off waiting for the multi-ligand docking code to get released (hopefully soon).

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