Partial Charges for Rare Atoms

Hi,

I'm working with a dataset containing SMILES strings of various ligands, and I want to calculate partial charges for each of them using either the Gasteiger or AM1BCC method.

Here is the Python code I'm using:

import rdkit
from rdkit import Chem
from rdkit.Chem import rdDistGeom
from openff.toolkit import Molecule

smiles = 'C[AsH]C' #  example SMILES

charge_method = 'gasteiget' #  or 'am1bcc'

try:
    rdkit_mol = Chem.MolFromSmiles(smiles)
    # Generate Conformer
    rdkit_mol.RemoveAllConformers()
    rdkit_mol = Chem.AddHs(rdkit_mol)
    params = rdDistGeom.ETKDGv3()
    params.randomSeed = 0xd06f00d
    params.numThreads = 4
    params.maxAttempts = 100
    rdDistGeom.EmbedMultipleConfs(rdkit_mol, 1, params)
    # Load to OpenFF
    openff_mol = Molecule.from_rdkit(rdkit_mol,allow_undefined_stereo=True)
except:
    openff_mol = Molecule.from_smiles(smiles,allow_undefined_stereo=True)
    openff_mol.generate_conformers(n_conformers=1)

openff_mol.assign_partial_charges(partial_charge_method='gasteiger')
print(openff_mol.partial_charges)

However, I've encountered a couple of issues:

1. Ligands with Radicals (?):

Example SMILES: [S]12[Fe]3[S]4[Fe]1[S]1[Fe]2[S]3[Fe]41
Ligand ID: SF4

Error:

[15:20:31] unrecognized bond type[15:20:31] unrecognized bond type[15:22:38] UFFTYPER: Unrecognized charge state for atom: 0
[15:22:38] UFFTYPER: Unrecognized atom type: Fe5+2 (1)
[15:22:38] UFFTYPER: Unrecognized charge state for atom: 2
[15:22:38] UFFTYPER: Unrecognized atom type: Fe5+2 (3)
[15:22:38] UFFTYPER: Unrecognized charge state for atom: 4
[15:22:38] UFFTYPER: Unrecognized atom type: Fe5+2 (5)
[15:22:38] UFFTYPER: Unrecognized charge state for atom: 6
[15:22:38] UFFTYPER: Unrecognized atom type: Fe5+2 (7)

RadicalsNotSupportedError: The OpenFF Toolkit does not currently support parsing molecules with S- and P-block radicals. Found 1 radical electrons on molecule [S]12[Fe]3[S]4[Fe]1[S]1[Fe]2[S]3[Fe]41.

Do you have any ideas how to omit that error?

2. Ligands with Atoms Lacking Parameters in Charge Calculation Methods:

List of Not Working Atoms in my DataSet

bad_atoms = ['Se','Fe','Ca','W','V','Co','As','Be','Mo','Te','Sb','Hg','Cr','Cu','Pd','Tb','Pr','Pb','Ir','Rh','Pt','Sn','Ni','Au','Zn','U','Ru','Cu']

Example SMILES: CCC1=C(C)C2=Cc3c(CC)c(C)c4n3[Rh@SP3]35n6c(c(C)c(CCC(=O)O)c6=CC6=[N+]3C(=C4)C(C)=C6CCC(=O)O)=CC1=[N+]25
Ligand ID: SF4

Error for Gasteigert:

[15:29:24] UFFTYPER: Unrecognized atom type: Rh3 (15)

Error for am1-bcc:


ValueError: No registered toolkits can provide the capability "assign_partial_charges" for args "()" and kwargs "{'molecule': Molecule with name '' and SMILES '[H][O][C](=[O])[C]([H])([H])[C]([H])([H])[C]1=[C]([C]([H])([H])[H])[C]2=[C]([H])[C]3=[N+]4[C](=[C]([H])[C]5=[C]([C]([H])([H])[C]([H])([H])[H])[C]([C]([H])([H])[H])=[C]6[C]([H])=[C]7[C]([C]([H])([H])[H])=[C]([C]([H])([H])[C]([H])([H])[C](=[O])[O][H])[C]8=[N+]7[Rh@@]4([N]2[C]1=[C]8[H])[N]65)[C]([C]([H])([H])[H])=[C]3[C]([H])([H])[C]([H])([H])[H]', 'partial_charge_method': 'am1bcc', 'use_conformers': None, 'strict_n_conformers': False, 'normalize_partial_charges': True, '_cls': <class 'openff.toolkit.topology.molecule.Molecule'>}"
Available toolkits are: [ToolkitWrapper around The RDKit version 2024.03.4, ToolkitWrapper around AmberTools version 22.0, ToolkitWrapper around Built-in Toolkit version None]
ToolkitWrapper around The RDKit version 2024.03.4 <class 'openff.toolkit.utils.exceptions.ChargeMethodUnavailableError'> : partial_charge_method 'am1bcc' is not available from RDKitToolkitWrapper. Available charge methods are {'mmff94': {}, 'gasteiger': {}}
ToolkitWrapper around AmberTools version 22.0 <class 'openff.toolkit.utils.exceptions.ConformerGenerationError'> : RDKit conformer generation failed.
ToolkitWrapper around Built-in Toolkit version None <class 'openff.toolkit.utils.exceptions.ChargeMethodUnavailableError'> : Partial charge method "am1bcc"" is not supported by the Built-in toolkit. Available charge methods are {'zeros': {'rec_confs': 0, 'min_confs': 0, 'max_confs': 0}, 'formal_charge': {'rec_confs': 0, 'min_confs': 0, 'max_confs': 0}}```

Output:

array([nan, nan, nan, nan, nan, nan, nan, nan, nan, nan, nan, nan, nan,
   nan, nan, nan, nan, nan, nan, nan, nan, nan, nan, nan, nan, nan,
   nan, nan, nan, nan, nan, nan, nan, nan, nan, nan, nan, nan, nan,
   nan, nan, nan, nan, nan, nan, nan, nan, nan, nan, nan, nan, nan,
   nan, nan, nan, nan, nan, nan, nan, nan, nan, nan, nan, nan, nan,
   nan, nan, nan, nan, nan, nan, nan, nan, nan, nan, nan, nan, nan,
   nan]) <Unit('elementary_charge')>

Is there any chance to obtain charges for ligands with these specific atoms?

Maciek

openforcefield / openff-toolkit

Partial Charges for Rare Atoms #1903

1. Ligands with Radicals (?):

2. Ligands with Atoms Lacking Parameters in Charge Calculation Methods: