Re: [Rdkit-discuss] Ligand conversion problem from 2D to 3D

[Greg L. <gre...@gm...>]

Hi Emre,

Both of those compounds look like they have conflicting stereochemistry
information in the ring systems, i.e. the stereo which is specified cannot
actually exist. There's something else going on as well (that looks like a
bug) but this is already a big enough problem.

The easiest thing to do with these compounds (or things which have this
kind of problem) is to just disable the stereochemistry entirely by
removing all instances of the @ symbol from the input strings:
In [26]: ps = rdDistGeom.ETKDGv3()

In [27]: m = Chem.AddHs(Chem.MolFromSmiles('COc1cc(Br)c(C[N+]2(CCOCC[C@H
]3CC[C@H]4C[C@H]3C4(C)C)CCO
    ...: CC2)cc1OC'.replace('@','')))

In [28]: rdDistGeom.EmbedMolecule(m,ps)
Out[28]: 0

In [29]: m = Chem.AddHs(Chem.MolFromSmiles('CC(C)(C)OC(=O)N[C@H
](C[Si](C)(C)C)C(=O)N1CCC[C@H]1C(=O)
    ...: N[C@@H](CCCCN)B1O[C@@H]2C[C@H]3C[C@@H](C3(C)C)[C@
]2(C)O1'.replace('@','')))

In [30]: rdDistGeom.EmbedMolecule(m,ps)
Out[30]: 0

-greg



On Tue, Feb 6, 2024 at 9:42 AM Emre Apaydın <emr...@gm...>
wrote:

> Thank you so much for your help. I managed to convert most of the
> molecules from 2D to 3D, but no matter which ETKDG version, which embedding
> parameter I try, I cannot convert these two molecules; ZINC000101210593,
> ZINC000196058327. Is there an alternative feature or method I can try? I
> would be grateful if you could help me. Thank you!
>
> He, Amy <he...@bu...>, 11 Oca 2024 Per, 01:58 tarihinde
> şunu yazdı:
>
>> Hi Emre!
>>
>>
>>
>> You can get more detailed info on failed conformer generations through
>> *rdDistGeom.EmbedFailureCauses*, see:
>>
>>
>> https://greglandrum.github.io/rdkit-blog/posts/2023-05-17-understanding-confgen-errors.html
>>
>>
>>
>> Bests,
>>
>>
>>
>>
>>
>> --
>>
>> Amy He
>>
>> Hadad Lab @ OSU
>>
>> He...@os...
>>
>>
>>
>> *From: *Emre Apaydın <emr...@gm...>
>> *Date: *Wednesday, January 10, 2024 at 8:47 AM
>> *To: *rdk...@li... <
>> rdk...@li...>
>> *Subject: *[Rdkit-discuss] Ligand conversion problem from 2D to 3D
>>
>> Hello, I want to convert the 2D ligands I downloaded as sdf format from
>> the ZINC library to 3D, but almost half of them are not converted to 3D.
>> Some of them are; ZINC000008214373, ZINC000001530666, ZINC000085545180. 208
>> ligands are not converted
>>
>> Hello,
>>
>>
>>
>> I want to convert the 2D ligands I downloaded as sdf format from the ZINC
>> library to 3D, but almost half of them are not converted to 3D. Some of
>> them are; ZINC000008214373, ZINC000001530666, ZINC000085545180. 208 ligands
>> are not converted to 3D in this way. When I run the script, I do not get
>> any warning or error in IDE. When I look at the output of my Try, Except
>> commands, I see "ZINC000008214373.sdf : rdDistGeom.EmbedMolecule(mol,
>> etkdgv3) = Failed
>> ZINC000008214373.sdf : rdForceFieldHelpers.UFFOptimizeMolecule(mol) =
>> Failed" It outputs like this for ligands that are not translated to 3D.
>> When I try different methods, the ligands are converted to 3D. I wonder if
>> there is something missing or wrong with my script. I would be grateful if
>> you can help me.
>>
>>
>>
>> Thank you!
>>
>>
>> ```
>> from rdkit import Chem
>> from rdkit.Chem import rdDistGeom
>> from rdkit.Chem import rdForceFieldHelpers
>> from rdkit.Chem import rdPartialCharges
>> import os
>>
>> ligands_dir = "ligands"
>> output_dir = "new_ligands"
>> status_file = "process_status.txt"
>>
>> if not os.path.exists(output_dir):
>>     os.makedirs(output_dir)
>>
>> sdf_files = [f for f in os.listdir(ligands_dir) if f.endswith(".sdf")]
>>
>> with open(status_file, 'w') as status:
>>     for sdf_file in sdf_files:
>>         input_path = os.path.join(ligands_dir, sdf_file)
>>         output_path = os.path.join(output_dir, sdf_file)
>>         mol = Chem.MolFromMolFile(input_path)
>>
>>         # Add hydrogens
>>         try:
>>             mol = Chem.AddHs(mol, addCoords=True)
>>         except:
>>             status.write(f"{sdf_file} : Chem.AddHs(mol) = Failed\\n")
>>             continue
>>
>>         # 3D embedding
>>         etkdgv3 = rdDistGeom.ETKDGv3()
>>         embed_status = rdDistGeom.EmbedMolecule(mol, etkdgv3)
>>         if embed_status == -1:
>>             status.write(f"{sdf_file} : rdDistGeom.EmbedMolecule(mol,
>> etkdgv3) = Failed\\n")
>>
>>         # Compute Gasteiger charges
>>         try:
>>             rdPartialCharges.ComputeGasteigerCharges(mol)
>>         except:
>>             status.write(f"{sdf_file} :
>> rdPartialCharges.ComputeGasteigerCharges(mol) = Failed\\n")
>>
>>         # UFF energy minimization
>>         try:
>>             rdForceFieldHelpers.UFFOptimizeMolecule(mol)
>>         except:
>>             status.write(f"{sdf_file} :
>> rdForceFieldHelpers.UFFOptimizeMolecule(mol) = Failed\\n")
>>
>>         Chem.MolToMolFile(mol, output_path)
>> ```
>>
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