Hi Alexis and Oli,
I have a workaround for these kinds of cases, getting modified residues that are part of a chain to run in Isolde.
Step 1: Fetch P1L from the CCD in chimera (don’t use the Isolde add ligand command)
Step 2: After adding hydrogens, use the Isolde interface to parametrize P1L but DO NOT use the available MD template. Instead, parametrize the selected residue, having ‘Override existing’ enabled. Maybe copy
and save the .xml file that’s created in the working directory for next time.
Step 3: Go to your cysteine that needs the palmitoylation and manually rebuild the residue to add the lipid. For that, use the ChimeraX structure modification tools. It takes a few minutes to manually rebuild
the cysteine atom by atom into the P1L residue. Don’t forget hydrogens.
Step 4: Now you can run Isolde directly on the model – if Isolde complains about the residue, you should be able to supply and rebuild the residue with the custom .xml file it created in step 2.
I got it to run on my end, and I have attached the .xml file for P1L and a little movie that shows that within a random ACG tripeptide the palmitoylation seems to run well in Isolde (though I don’t have a
map, but fingers crossed that doesn’t change much).
I got this method to work with modified protein and also modified nucleic acid. Sometimes, this method rebuilds residues to have an atom or two too many where the modified residues connect with the rest of
the chain (for example an extra oxygen in a phosphate diester link in an RNA chain). In that case, just manually delete the extra atoms before real space refinement and let phenix take care of the exact geometry and bond lengths.
Would be curious if this works for other people as well and if Tristan approves,
Cheers
Paul