Parametrizing Protein with TPO Residue

[amarye]

I was trying to parametrize a protein with a TPO residue, but I encountered an error. Could you please help me?

protein_prep.txt

[jmichel80]

can you post more information about the error ? the posted text file is just a PDB

[amarye]

Thank you for your reply. This is an error I encountered when I wanted to parameterize the protein.

[akalpokas]

Hi @amarye, the reason the parametrization is failing is most likely due to the TPO residue being present in your protein. Amber FF14SB forcefield does not include parameters for it, so when you're trying to use the BSS.Parameters.ff14SB, tLEaP won't have the parameters for that residue. You can confirm this by adding a work_dir=tmp or something along those lines to BSS.Parameters.ff14SB, which will create a folder containing all of the tLEaP outputs and errors.

Luckily, ff14SB and ff19SB variants containing parameters for phosphorylated residues (including TPO) just got released: https://pubs.acs.org/doi/10.1021/acs.jctc.4c00732

I would recommend you manually parametrise your protein with tLEaP using these forcefields, and then you should be able to load in a fully parametrized system into BioSimSpace and continue as normal.

[jmichel80]

hi @amarye

there are a few issues highlighted by pdb4amber that needs attention before tLeap could work

-as @akalpokas mentionned you need to provide parameters for TPO. See the pre_mol_commands keyword argument described at the end of https://biosimspace.openbiosim.org/api/index_Parameters.html

• the gap between residues 163 and 165 suggests there are missing residues in 6c9j.pdb. This should be fixed to make sure you are simulating the correct structure.

[amarye]

Hi @akalpokas , @jmichel80

Thank you for your detailed explanation and guidance! I appreciate the information about the ff14SB and ff19SB force fields that support phosphorylated residues like TPO. I will definitely look into using tLEaP with the pre_mol_commands option to include the necessary parameters.

Also, I’ll make sure to address the missing residues issue in the 6c9j.pdb file before proceeding. Your help has been invaluable!

Thanks again!