Simulating a metallo-protein with 2 ligands

[sadiogo]

Hi, I found in the closed issues a notebook to run simulation with two ligands. However, my protein also has a Mn ion. Is it currently possible to run this type of simulation? If so, I should keep the Mn ion with the protein PDB and apply AMBER force field?

[sadiogo]

I tried running the 2-ligand notebook with Mn in the protein pdb. First I got a minimization error which I overcame by not adding hydrogens and providing all files with correct protonation state. However, now I am getting the following error:

[19:51:12] Explicit valence for atom # 12 O, 3, is greater than permitted
---------------------------------------------------------------------------
ArgumentError                             Traceback (most recent call last)
[<ipython-input-6-955e71b4dc31>](https://localhost:8080/#) in <cell line: 98>()
     96 
     97 #fix ligands
---> 98 charge1 = minimize_ligand_charge(ligand1_pdb, ligand1_pdb2)
     99 charge2 = minimize_ligand_charge(ligand2_pdb, ligand2_pdb2)
    100 

[<ipython-input-6-955e71b4dc31>](https://localhost:8080/#) in minimize_ligand_charge(input, output)
     81     hmol = Chem.MolFromMolFile('temp.mol', removeHs=False)
     82     # hmol = Chem.AddHs(mol)
---> 83     mp = AllChem.MMFFGetMoleculeProperties(hmol)
     84     ff = AllChem.MMFFGetMoleculeForceField(hmol, mp)
     85     for a in hmol.GetAtoms():

ArgumentError: Python argument types in
    rdkit.Chem.rdForceFieldHelpers.MMFFGetMoleculeProperties(NoneType)
did not match C++ signature:
    MMFFGetMoleculeProperties(RDKit::ROMol {lvalue} mol, std::__cxx11::basic_string<char, std::char_traits<char>, std::allocator<char> > mmffVariant='MMFF94', unsigned int mmffVerbosity=0)

I looked in the Bonds Block of the connection table in temp.mol file and found that atom # 12 does perform 3 bonds, but when I look it up in the Atom Block of the table, the 12th line of the block is actually a Nitrogen, and not an Oxygen like has been stated in the error. Does this make sense? I have attached the temp.mol file.
temp.mol.txt

[pablo-arantes]

Hi Diogo,

Thank you for letting me know about the issue.
The notebook for 2-ligands has not been updated. I will take a look in your error and try to change and update the code.
Regarding Mn ion, I need to check the code as well to check if the notebook accepts ions in protein PDB.

I will back to you, as soon as possible.

Thank you.

Best,

Pablo

[sadiogo]

Hi Pablo!

I'm looking forward to the updated notebook for 2 ligands!

[pablo-arantes]

Hi @sadiogo,

I have a lot of things on my plate right now. So, I will try to fix the code in the end of this week.

I hope you understand.

Thank you.

Best,

Pablo

[sadiogo]

No worries! I totally understand.

All the best,
Diogo

[jochuan]

I don't know if this is related but i am trying to run a simulation with two ligands on the same pdb file but i am getting this error on the input cell:

OSError Traceback (most recent call last)
in <cell line: 71>()
70
71 if Add_ligand_hydrogens == "Yes":
---> 72 mol= [m for m in pybel.readfile(filename=ligand_pdb, format='pdb')][0]
73 out=pybel.Outputfile(filename="temp.mol",format='mol',overwrite=True)
74 out.write(mol)

/usr/local/lib/python3.10/site-packages/openbabel/pybel.py in readfile(format, filename, opt)
159 raise ValueError("%s is not a recognised Open Babel format" % format)
160 if not os.path.isfile(filename):
--> 161 raise IOError("No such file: '%s'" % filename)
162
163 def filereader():

Is there something that i need to do for it to work or it is a currently bug when trying to run simulations with more than one ligand ?
Forget about it i think that i figured out my error

[jochuan]

Yeah looks like i have the same problem trying to do a simulation with a heme ligand which contains a Fe atom:

[19:24:51] Explicit valence for atom # 9 N, 4, is greater than permitted

ArgumentError Traceback (most recent call last)
in <cell line: 71>()
76
77 mol = Chem.MolFromMolFile('temp.mol', removeHs=True)
---> 78 hmol = Chem.AddHs(mol)
79 mp = AllChem.MMFFGetMoleculeProperties(hmol)
80 ff = AllChem.MMFFGetMoleculeForceField(hmol, mp)

ArgumentError: Python argument types in
rdkit.Chem.rdmolops.AddHs(NoneType)
did not match C++ signature:
AddHs(RDKit::ROMol mol, bool explicitOnly=False, bool addCoords=False, boost::python::api::object onlyOnAtoms=None, bool addResidueInfo=False)

And this was on the main notebook for protein-ligand simulations