rdkit-discuss — Mailing list for discussion, questions and answers.

[Rdkit-discuss] [MSc] [PhD] [Post-Doc] Computational Chemistry Research Group.

[Eduardo M. <edu...@gm...>]

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[Rdkit-discuss] Reaction SMILES to MRV or RXN format

[Santiago F. <san...@me...>]

Good morning
      I am trying to convert some reactions in SMILES format to RXN and MRV format, but I am not able to obtain
      a good representation. The reaction components are really messed up in the final output.

      For example, using this reaction SMILES, these are the steps I am following:

     string reaction = "C.CO>cno.NN>coc.[H][H]";

     RDKit::ChemicalReaction* result = RDKit::RxnSmartsToChemicalReaction(reaction, nullptr, true, true);
     RDDepict::compute2DCoordsForReaction(*result);

     string mrvReaction = RDKit::ChemicalReactionToMrvBlock(*result, false);
     or
     string rxnReaction = RDKit::ChemicalReactionToRxnBlock(*result, true, true);

     I am attaching both results.

 Best regards
 Santiago

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

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

Hi Amy,

On Tue, Feb 6, 2024 at 8:20 PM He, Amy <he...@bu...> wrote:

>
>
> Emre, great to hear from you. I also just wanted to say that not all
> entries in ZINC can be transformed into 3D structures. We encountered a
> couple of instances where the annotated stereo is nonphysical, especially
> at closely-spaced stereo centers in small cycles. I had thought to design a
> check to capture these instances, but eventually I just gave up and
> discarded the entries because no other available methods (including ETKDG)
> or software can build 3D structures for 3D calculations. It would still be
> helpful to consider a check even for 2D calculations.
>
>
Yeah, this is a difficult one. It would be nice to have a check to catch at
least the "simple" cases like these cage structures where there's only one
possible relative stereo possible, but I haven't managed to find it yet.

-greg

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

[He, A. <he...@bu...>]

Hi Greg,

Thanks so much for your kind suggestions. That also helped with our projects!

Emre, great to hear from you. I also just wanted to say that not all entries in ZINC can be transformed into 3D structures. We encountered a couple of instances where the annotated stereo is nonphysical, especially at closely-spaced stereo centers in small cycles. I had thought to design a check to capture these instances, but eventually I just gave up and discarded the entries because no other available methods (including ETKDG) or software can build 3D structures for 3D calculations. It would still be helpful to consider a check even for 2D calculations.

Best regards,
Amy


From: Greg Landrum <gre...@gm...>
Date: Tuesday, February 6, 2024 at 6:44 AM
To: Emre Apaydın <emr...@gm...>
Cc: He, Amy <he...@bu...>, rdk...@li... <rdk...@li...>
Subject: Re: [Rdkit-discuss] Ligand conversion problem from 2D to 3D
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)

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...<mailto: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...<mailto: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<https://urldefense.com/v3/__https:/greglandrum.github.io/rdkit-blog/posts/2023-05-17-understanding-confgen-errors.html__;!!KGKeukY!zC3dbTgBTpt6IY3K9mQhnSMqzjaX5IpXP3eSNuuiYvDoiIL42h3Xzv5cqkiPUC-E9jJku-W-Wyl54FstHYVR9uYkJGCMiB5D0Q$>

Bests,


--
Amy He
Hadad Lab @ OSU
He...@os...<mailto:He...@os...>

From: Emre Apaydın <emr...@gm...<mailto:emr...@gm...>>
Date: Wednesday, January 10, 2024 at 8:47 AM
To: rdk...@li...<mailto:rdk...@li...> <rdk...@li...<mailto: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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https://lists.sourceforge.net/lists/listinfo/rdkit-discuss<https://urldefense.com/v3/__https:/lists.sourceforge.net/lists/listinfo/rdkit-discuss__;!!KGKeukY!zC3dbTgBTpt6IY3K9mQhnSMqzjaX5IpXP3eSNuuiYvDoiIL42h3Xzv5cqkiPUC-E9jJku-W-Wyl54FstHYVR9uYkJGBfYAHZhw$>

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)
>> ```
>>
> _______________________________________________
> Rdkit-discuss mailing list
> Rdk...@li...
> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>

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

[Emre A. <emr...@gm...>]

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)
> ```
>

Re: [Rdkit-discuss] One tautomer not included in list of enumerated tautomers

[Lewis M. <lew...@gm...>]

Good catch, thank you Diogo!

Recognising the difficulties of tautomer enumeration: For my own purposes,
the ideal behaviour would be to get the set of all three plausible
tautomers of 'mol1' no matter what the input SMILES. Looks like there's
already a Github Issue up (https://github.com/rdkit/rdkit/issues/5937) but
I can add this if it has a different cause.

thanks all
Lewis



On Tue, Feb 6, 2024 at 7:23 AM Diogo Martins <dio...@gm...> wrote:

> Hello,
>
> I think it's a bug because the tautomers depend on how the input SMILES is
> written. Both represent mol1:
>
> Sc1ncc2c(c1)cccc2
> Sc1cc2ccccc2cn1
>
> However the resulting tautomers differ depending on which is used as input.
>
> Best regards,
> Diogo
>
> On Mon, 5 Feb 2024 at 11:38, Lewis Martin <lew...@gm...>
> wrote:
>
>> Thank you very much for the detective work, Wim! This is helpful.
>>
>> It looks like the _reverse_ transition is possible, though. If I start by
>> generating tautomers of "mol2", then "mol1" is recovered, which indicates
>> this is an allowed transform. Is it possible that one direction is allowed
>> but not the reverse?
>>
>> Failing a solution there, does anyone know if it is possible to add
>> SMIRKS to the allowed tautomers through the python interface?
>> Thanks,
>> Lewis
>>
>> On Mon, Feb 5, 2024 at 9:52 PM Wim Dehaen <wim...@gm...> wrote:
>>
>>> hi lewis,
>>> if i am not mistaken this is because the tautomer transfor "1,3 aromatic
>>> heteroatom H shift" does not account for other chalcogens than oxygen, so
>>> no selenium, tellurium or sulfur.
>>> you can find the list of transforms here:
>>> https://github.com/rdkit/rdkit/blob/8dae48b7a17fd984c69d04549e6d9b53690f5c52/Code/GraphMol/MolStandardize/TautomerCatalog/tautomerTransforms.in#L46
>>> (poiting to the line with the relevant transform).
>>> best wishes
>>> wim
>>>
>>> On Mon, Feb 5, 2024 at 3:26 AM Lewis Martin <lew...@gm...>
>>> wrote:
>>>
>>>> Hi all,
>>>> I'm looking at scoring tautomers, and using the 'tautobase' dataset
>>>> used by Weider et al* at:
>>>>
>>>> https://github.com/choderalab/neutromeratio/blob/master/data/b3lyp_tautobase_subset.txt
>>>>
>>>> This dataset has pairs of tautomers with experimental logK values to
>>>> determine the preferred tautomer.
>>>>
>>>> In at least one case, depending on which tautomer you use as the
>>>> 'entry' point, the enumerated tautomers by RDKit either do or don't include
>>>> both of the pair of input molecules. *I'm hoping there's a way to
>>>> uniquely recover the full set of possible tautomers from using any input
>>>> tautomer. *
>>>>
>>>> Here's a code example:
>>>>
>>>> from rdkit import Chem
>>>>>
>>>> from rdkit.Chem import Draw
>>>>
>>>> from rdkit.Chem.Draw import IPythonConsole
>>>>> IPythonConsole.drawOptions.addStereoAnnotation = True
>>>>> from rdkit.Chem.MolStandardize import rdMolStandardize
>>>>>
>>>>> #same result if you don't do any of these params.
>>>>
>>>> tautomer_params =
>>>>> Chem.MolStandardize.rdMolStandardize.CleanupParameters()
>>>>> tautomer_params.tautomerRemoveSp3Stereo = False
>>>>> tautomer_params.tautomerRemoveBondStereo = False
>>>>> tautomer_params.tautomerRemoveIsotopicHs = False
>>>>> tautomer_params.tautomerReassignStereo = False
>>>>> tautomer_params.doCanonical = True
>>>>>
>>>>> enumerator = rdMolStandardize.TautomerEnumerator(tautomer_params)
>>>>>
>>>>> smi1 = 'Sc1cc2ccccc2cn1'
>>>>> smi2 = 'S=c1cc2ccccc2c[nH]1'
>>>>> mol1 = Chem.MolFromSmiles(smi1)
>>>>> mol2 = Chem.MolFromSmiles(smi2)
>>>>>
>>>>> #choose mol1 or mol2 to be source of tautomers:
>>>>> #choose mol1, and look at the tautomers. Note that mol2 isn't present!
>>>>> tauts = [Chem.MolFromSmiles(Chem.MolToSmiles(m)) for m in
>>>>> enumerator.Enumerate(mol1)]
>>>>>
>>>>> Draw.MolsToGridImage([mol1, mol2]+tauts, legends=['mol1', 'mol2 (not
>>>>> present in tauts!)'] + [f'taut{i}' for i in range(len(tauts))],
>>>>>                      molsPerRow=4)
>>>>>
>>>>
>>>> And a picture of this in a notebook for an at-a-glance view:
>>>> https://gist.github.com/ljmartin/4a9d9eb684df3e11e59fc6502a4b7b03
>>>>
>>>> Does anyone know a way to recover "mol2" within tautomers of "mol1"?
>>>>
>>>> Thank you!
>>>> Lewis
>>>>
>>>>
>>>> _______________________________________________
>>>> Rdkit-discuss mailing list
>>>> Rdk...@li...
>>>> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>>>>
>>> _______________________________________________
>> Rdkit-discuss mailing list
>> Rdk...@li...
>> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>>
>

Re: [Rdkit-discuss] One tautomer not included in list of enumerated tautomers

[Diogo M. <dio...@gm...>]

Hello,

I think it's a bug because the tautomers depend on how the input SMILES is
written. Both represent mol1:

Sc1ncc2c(c1)cccc2
Sc1cc2ccccc2cn1

However the resulting tautomers differ depending on which is used as input.

Best regards,
Diogo

On Mon, 5 Feb 2024 at 11:38, Lewis Martin <lew...@gm...> wrote:

> Thank you very much for the detective work, Wim! This is helpful.
>
> It looks like the _reverse_ transition is possible, though. If I start by
> generating tautomers of "mol2", then "mol1" is recovered, which indicates
> this is an allowed transform. Is it possible that one direction is allowed
> but not the reverse?
>
> Failing a solution there, does anyone know if it is possible to add SMIRKS
> to the allowed tautomers through the python interface?
> Thanks,
> Lewis
>
> On Mon, Feb 5, 2024 at 9:52 PM Wim Dehaen <wim...@gm...> wrote:
>
>> hi lewis,
>> if i am not mistaken this is because the tautomer transfor "1,3 aromatic
>> heteroatom H shift" does not account for other chalcogens than oxygen, so
>> no selenium, tellurium or sulfur.
>> you can find the list of transforms here:
>> https://github.com/rdkit/rdkit/blob/8dae48b7a17fd984c69d04549e6d9b53690f5c52/Code/GraphMol/MolStandardize/TautomerCatalog/tautomerTransforms.in#L46
>> (poiting to the line with the relevant transform).
>> best wishes
>> wim
>>
>> On Mon, Feb 5, 2024 at 3:26 AM Lewis Martin <lew...@gm...>
>> wrote:
>>
>>> Hi all,
>>> I'm looking at scoring tautomers, and using the 'tautobase' dataset used
>>> by Weider et al* at:
>>>
>>> https://github.com/choderalab/neutromeratio/blob/master/data/b3lyp_tautobase_subset.txt
>>>
>>> This dataset has pairs of tautomers with experimental logK values to
>>> determine the preferred tautomer.
>>>
>>> In at least one case, depending on which tautomer you use as the 'entry'
>>> point, the enumerated tautomers by RDKit either do or don't include both of
>>> the pair of input molecules. *I'm hoping there's a way to uniquely
>>> recover the full set of possible tautomers from using any input tautomer. *
>>>
>>> Here's a code example:
>>>
>>> from rdkit import Chem
>>>>
>>> from rdkit.Chem import Draw
>>>
>>> from rdkit.Chem.Draw import IPythonConsole
>>>> IPythonConsole.drawOptions.addStereoAnnotation = True
>>>> from rdkit.Chem.MolStandardize import rdMolStandardize
>>>>
>>>> #same result if you don't do any of these params.
>>>
>>> tautomer_params =
>>>> Chem.MolStandardize.rdMolStandardize.CleanupParameters()
>>>> tautomer_params.tautomerRemoveSp3Stereo = False
>>>> tautomer_params.tautomerRemoveBondStereo = False
>>>> tautomer_params.tautomerRemoveIsotopicHs = False
>>>> tautomer_params.tautomerReassignStereo = False
>>>> tautomer_params.doCanonical = True
>>>>
>>>> enumerator = rdMolStandardize.TautomerEnumerator(tautomer_params)
>>>>
>>>> smi1 = 'Sc1cc2ccccc2cn1'
>>>> smi2 = 'S=c1cc2ccccc2c[nH]1'
>>>> mol1 = Chem.MolFromSmiles(smi1)
>>>> mol2 = Chem.MolFromSmiles(smi2)
>>>>
>>>> #choose mol1 or mol2 to be source of tautomers:
>>>> #choose mol1, and look at the tautomers. Note that mol2 isn't present!
>>>> tauts = [Chem.MolFromSmiles(Chem.MolToSmiles(m)) for m in
>>>> enumerator.Enumerate(mol1)]
>>>>
>>>> Draw.MolsToGridImage([mol1, mol2]+tauts, legends=['mol1', 'mol2 (not
>>>> present in tauts!)'] + [f'taut{i}' for i in range(len(tauts))],
>>>>                      molsPerRow=4)
>>>>
>>>
>>> And a picture of this in a notebook for an at-a-glance view:
>>> https://gist.github.com/ljmartin/4a9d9eb684df3e11e59fc6502a4b7b03
>>>
>>> Does anyone know a way to recover "mol2" within tautomers of "mol1"?
>>>
>>> Thank you!
>>> Lewis
>>>
>>>
>>> _______________________________________________
>>> Rdkit-discuss mailing list
>>> Rdk...@li...
>>> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>>>
>> _______________________________________________
> Rdkit-discuss mailing list
> Rdk...@li...
> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>

Re: [Rdkit-discuss] One tautomer not included in list of enumerated tautomers

[Lewis M. <lew...@gm...>]

Thank you very much for the detective work, Wim! This is helpful.

It looks like the _reverse_ transition is possible, though. If I start by
generating tautomers of "mol2", then "mol1" is recovered, which indicates
this is an allowed transform. Is it possible that one direction is allowed
but not the reverse?

Failing a solution there, does anyone know if it is possible to add SMIRKS
to the allowed tautomers through the python interface?
Thanks,
Lewis

On Mon, Feb 5, 2024 at 9:52 PM Wim Dehaen <wim...@gm...> wrote:

> hi lewis,
> if i am not mistaken this is because the tautomer transfor "1,3 aromatic
> heteroatom H shift" does not account for other chalcogens than oxygen, so
> no selenium, tellurium or sulfur.
> you can find the list of transforms here:
> https://github.com/rdkit/rdkit/blob/8dae48b7a17fd984c69d04549e6d9b53690f5c52/Code/GraphMol/MolStandardize/TautomerCatalog/tautomerTransforms.in#L46
> (poiting to the line with the relevant transform).
> best wishes
> wim
>
> On Mon, Feb 5, 2024 at 3:26 AM Lewis Martin <lew...@gm...>
> wrote:
>
>> Hi all,
>> I'm looking at scoring tautomers, and using the 'tautobase' dataset used
>> by Weider et al* at:
>>
>> https://github.com/choderalab/neutromeratio/blob/master/data/b3lyp_tautobase_subset.txt
>>
>> This dataset has pairs of tautomers with experimental logK values to
>> determine the preferred tautomer.
>>
>> In at least one case, depending on which tautomer you use as the 'entry'
>> point, the enumerated tautomers by RDKit either do or don't include both of
>> the pair of input molecules. *I'm hoping there's a way to uniquely
>> recover the full set of possible tautomers from using any input tautomer. *
>>
>> Here's a code example:
>>
>> from rdkit import Chem
>>>
>> from rdkit.Chem import Draw
>>
>> from rdkit.Chem.Draw import IPythonConsole
>>> IPythonConsole.drawOptions.addStereoAnnotation = True
>>> from rdkit.Chem.MolStandardize import rdMolStandardize
>>>
>>> #same result if you don't do any of these params.
>>
>> tautomer_params = Chem.MolStandardize.rdMolStandardize.CleanupParameters()
>>> tautomer_params.tautomerRemoveSp3Stereo = False
>>> tautomer_params.tautomerRemoveBondStereo = False
>>> tautomer_params.tautomerRemoveIsotopicHs = False
>>> tautomer_params.tautomerReassignStereo = False
>>> tautomer_params.doCanonical = True
>>>
>>> enumerator = rdMolStandardize.TautomerEnumerator(tautomer_params)
>>>
>>> smi1 = 'Sc1cc2ccccc2cn1'
>>> smi2 = 'S=c1cc2ccccc2c[nH]1'
>>> mol1 = Chem.MolFromSmiles(smi1)
>>> mol2 = Chem.MolFromSmiles(smi2)
>>>
>>> #choose mol1 or mol2 to be source of tautomers:
>>> #choose mol1, and look at the tautomers. Note that mol2 isn't present!
>>> tauts = [Chem.MolFromSmiles(Chem.MolToSmiles(m)) for m in
>>> enumerator.Enumerate(mol1)]
>>>
>>> Draw.MolsToGridImage([mol1, mol2]+tauts, legends=['mol1', 'mol2 (not
>>> present in tauts!)'] + [f'taut{i}' for i in range(len(tauts))],
>>>                      molsPerRow=4)
>>>
>>
>> And a picture of this in a notebook for an at-a-glance view:
>> https://gist.github.com/ljmartin/4a9d9eb684df3e11e59fc6502a4b7b03
>>
>> Does anyone know a way to recover "mol2" within tautomers of "mol1"?
>>
>> Thank you!
>> Lewis
>>
>>
>> _______________________________________________
>> Rdkit-discuss mailing list
>> Rdk...@li...
>> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>>
>

Re: [Rdkit-discuss] One tautomer not included in list of enumerated tautomers

[Wim D. <wim...@gm...>]

hi lewis,
if i am not mistaken this is because the tautomer transfor "1,3 aromatic
heteroatom H shift" does not account for other chalcogens than oxygen, so
no selenium, tellurium or sulfur.
you can find the list of transforms here:
https://github.com/rdkit/rdkit/blob/8dae48b7a17fd984c69d04549e6d9b53690f5c52/Code/GraphMol/MolStandardize/TautomerCatalog/tautomerTransforms.in#L46
(poiting to the line with the relevant transform).
best wishes
wim

On Mon, Feb 5, 2024 at 3:26 AM Lewis Martin <lew...@gm...>
wrote:

> Hi all,
> I'm looking at scoring tautomers, and using the 'tautobase' dataset used
> by Weider et al* at:
>
> https://github.com/choderalab/neutromeratio/blob/master/data/b3lyp_tautobase_subset.txt
>
> This dataset has pairs of tautomers with experimental logK values to
> determine the preferred tautomer.
>
> In at least one case, depending on which tautomer you use as the 'entry'
> point, the enumerated tautomers by RDKit either do or don't include both of
> the pair of input molecules. *I'm hoping there's a way to uniquely
> recover the full set of possible tautomers from using any input tautomer. *
>
> Here's a code example:
>
> from rdkit import Chem
>>
> from rdkit.Chem import Draw
>
> from rdkit.Chem.Draw import IPythonConsole
>> IPythonConsole.drawOptions.addStereoAnnotation = True
>> from rdkit.Chem.MolStandardize import rdMolStandardize
>>
>> #same result if you don't do any of these params.
>
> tautomer_params = Chem.MolStandardize.rdMolStandardize.CleanupParameters()
>> tautomer_params.tautomerRemoveSp3Stereo = False
>> tautomer_params.tautomerRemoveBondStereo = False
>> tautomer_params.tautomerRemoveIsotopicHs = False
>> tautomer_params.tautomerReassignStereo = False
>> tautomer_params.doCanonical = True
>>
>> enumerator = rdMolStandardize.TautomerEnumerator(tautomer_params)
>>
>> smi1 = 'Sc1cc2ccccc2cn1'
>> smi2 = 'S=c1cc2ccccc2c[nH]1'
>> mol1 = Chem.MolFromSmiles(smi1)
>> mol2 = Chem.MolFromSmiles(smi2)
>>
>> #choose mol1 or mol2 to be source of tautomers:
>> #choose mol1, and look at the tautomers. Note that mol2 isn't present!
>> tauts = [Chem.MolFromSmiles(Chem.MolToSmiles(m)) for m in
>> enumerator.Enumerate(mol1)]
>>
>> Draw.MolsToGridImage([mol1, mol2]+tauts, legends=['mol1', 'mol2 (not
>> present in tauts!)'] + [f'taut{i}' for i in range(len(tauts))],
>>                      molsPerRow=4)
>>
>
> And a picture of this in a notebook for an at-a-glance view:
> https://gist.github.com/ljmartin/4a9d9eb684df3e11e59fc6502a4b7b03
>
> Does anyone know a way to recover "mol2" within tautomers of "mol1"?
>
> Thank you!
> Lewis
>
>
> _______________________________________________
> Rdkit-discuss mailing list
> Rdk...@li...
> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>

[Rdkit-discuss] One tautomer not included in list of enumerated tautomers

[Lewis M. <lew...@gm...>]

Hi all,
I'm looking at scoring tautomers, and using the 'tautobase' dataset used by
Weider et al* at:
https://github.com/choderalab/neutromeratio/blob/master/data/b3lyp_tautobase_subset.txt

This dataset has pairs of tautomers with experimental logK values to
determine the preferred tautomer.

In at least one case, depending on which tautomer you use as the 'entry'
point, the enumerated tautomers by RDKit either do or don't include both of
the pair of input molecules. *I'm hoping there's a way to uniquely recover
the full set of possible tautomers from using any input tautomer. *

Here's a code example:

from rdkit import Chem
>
from rdkit.Chem import Draw

from rdkit.Chem.Draw import IPythonConsole
> IPythonConsole.drawOptions.addStereoAnnotation = True
> from rdkit.Chem.MolStandardize import rdMolStandardize
>
> #same result if you don't do any of these params.

tautomer_params = Chem.MolStandardize.rdMolStandardize.CleanupParameters()
> tautomer_params.tautomerRemoveSp3Stereo = False
> tautomer_params.tautomerRemoveBondStereo = False
> tautomer_params.tautomerRemoveIsotopicHs = False
> tautomer_params.tautomerReassignStereo = False
> tautomer_params.doCanonical = True
>
> enumerator = rdMolStandardize.TautomerEnumerator(tautomer_params)
>
> smi1 = 'Sc1cc2ccccc2cn1'
> smi2 = 'S=c1cc2ccccc2c[nH]1'
> mol1 = Chem.MolFromSmiles(smi1)
> mol2 = Chem.MolFromSmiles(smi2)
>
> #choose mol1 or mol2 to be source of tautomers:
> #choose mol1, and look at the tautomers. Note that mol2 isn't present!
> tauts = [Chem.MolFromSmiles(Chem.MolToSmiles(m)) for m in
> enumerator.Enumerate(mol1)]
>
> Draw.MolsToGridImage([mol1, mol2]+tauts, legends=['mol1', 'mol2 (not
> present in tauts!)'] + [f'taut{i}' for i in range(len(tauts))],
>                      molsPerRow=4)
>

And a picture of this in a notebook for an at-a-glance view:
https://gist.github.com/ljmartin/4a9d9eb684df3e11e59fc6502a4b7b03

Does anyone know a way to recover "mol2" within tautomers of "mol1"?

Thank you!
Lewis

Re: [Rdkit-discuss] Redirect error messages to a file in Python?

[David C. <dav...@gm...>]

Thanks Joel,
That's really helpful.  Armed with that information, I was able to dig
further into the source code and find some unit tests that do very similar
to what you have set up, but within a context manager.  Hopefully the mail
client won't mangle the formatting.

Cheers,
Dave


#!/usr/bin/env python

import logging

from contextlib import contextmanager
from io import StringIO

from rdkit import rdBase, Chem

@contextmanager
def log_to_python(level=None):
  """
    Temporarily redirect logging to Python streams, optionally
    setting a specific log level.
  """
  rdBase.LogToPythonLogger()
  pylog = logging.getLogger("rdkit")
  if level is not None:
    original_level = pylog.level
    pylog.setLevel(level)

  yield pylog

  if level is not None:
    pylog.setLevel(original_level)
  rdBase.LogToCppStreams()


@contextmanager
def capture_logging(level=None):
  """
    Temporarily redirect logging to a Python StringIO, optionally
    setting a specific log level.
  """
  log_stream = StringIO()
  stream_handler = logging.StreamHandler(stream=log_stream)

  with log_to_python(level) as pylog:
    pylog.addHandler(stream_handler)

    yield log_stream

    pylog.removeHandler(stream_handler)


with capture_logging(logging.WARNING) as log_stream:

    mol = Chem.MolFromSmiles('c1ccccc1(C)(C)')
    print(f'and the message is {log_stream.getvalue()}')
    # this clears the log message.  If you want to keep all the messages
    # as one long string, don't do this.
    log_stream.truncate(0)

    mol = Chem.MolFromSmiles('C(C)(C)(C)(C)C')
    print(f'and now the message is {log_stream.getvalue()}')




On Thu, Feb 1, 2024 at 9:20 PM Joel Duerksen <jo...@d2...> wrote:

> I've changed my strategy a few times. I'll share my most recent approach,
> quite possibly this is flawed, but for now it works for me.  Fixes and
> corrections welcome.
> I think these are all the relevant bits below...
>
> ...
> ... other stuff, import rdkit, etc...
> ...
> # fancy foot work to capture RDKIT messages
> from io import StringIO
> from rdkit import rdBase
> rdBase.LogToPythonLogger()
>
> import logging
> logger = logging.getLogger('rdkit')
> logger.setLevel(logging.WARNING) # make explicit though this is the
> default, currently
>
> ... more code...
> ... I'll show some of the context of how I'm using it..  reading an SDF
> file here, and want to trap every message
>
>         f_in = open_sdf(INPUT_FILE, 'rb')
>         # please don't change the molecule while reading it in
>         suppl = Chem.ForwardSDMolSupplier(f_in, sanitize=False,
> removeHs=False, strictParsing=False)
>
>         with StringIO() as log_stream:
>             log_handler = logging.StreamHandler(log_stream)
>             myLogger = logging.getLogger('rdkit')
>             myLogger.addHandler(log_handler)
>
>             # usually don't pull from a generator this way, but we're
> trying to catch log messages for each molecule individually
>             while True:
>                 try:
>                     # Python 3
>                     log_stream.truncate(0)
>                     log_stream.seek(0)
>                     curmol = next(suppl)
>                 except StopIteration:
>                     break
>
> ... capture everything in the stream from reading the molecule with
> log_stream.getvalue()
>             re.sub(r'\[[0-9]{2}:[0-9]{2}:[0-9]{2}[^]]*\]', '',
> log_stream.getvalue()) # remove the timestamps [12:14:19] (maybe could turn
> them off?)
>
> ... after closing SDF file I'm removing the handler
>         # remove our log handler
>         myLogger.handlers.clear()
>
>
> On Thu, Feb 1, 2024 at 12:49 PM David Cosgrove <dav...@gm...>
> wrote:
>
>> Hi,
>> I'd like to be able to redirect the various logging streams to files from
>> within the code.  I know that I can turn them off:
>>
>> RDLogger.DisableLog('rdApp.*')
>>
>> but that's more extreme than I want.
>> I have found the function RDLogger.AttachFileToLog() but can't work out
>> how to use it.  The naive
>>
>> RDLogger.AttachFileToLog('rdApp.*', 'logging.file', 1)
>>
>> didn't produce a file anywhere I could see.  I have not been able to find
>> an example of its use.
>>
>> find . -name \*.py -exec grep AttachFileToLog {} \; -print
>>
>> from the top of the source tree produces
>>
>> from rdkit.rdBase import AttachFileToLog, DisableLog, EnableLog,
>> LogMessage
>> ./rdkit/RDLogger.py
>>
>> but the functions don't seem to be used within that file.
>>
>> Any pointers gratefully received.
>> Dave
>>
>>
>> --
>> David Cosgrove
>> Freelance computational chemistry and chemoinformatics developer
>> http://cozchemix.co.uk
>>
>> _______________________________________________
>> Rdkit-discuss mailing list
>> Rdk...@li...
>> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>>
>
>
> --
> Regards,
>      Joel
>
> ----
> *Joel L. Duerksen     *jo...@d2...
> *Innovative Machine Learning and Data Science Solutions*
>
>

-- 
David Cosgrove
Freelance computational chemistry and chemoinformatics developer
http://cozchemix.co.uk

Re: [Rdkit-discuss] Redirect error messages to a file in Python?

[Joel D. <jo...@d2...>]

I've changed my strategy a few times. I'll share my most recent approach,
quite possibly this is flawed, but for now it works for me.  Fixes and
corrections welcome.
I think these are all the relevant bits below...

...
... other stuff, import rdkit, etc...
...
# fancy foot work to capture RDKIT messages
from io import StringIO
from rdkit import rdBase
rdBase.LogToPythonLogger()

import logging
logger = logging.getLogger('rdkit')
logger.setLevel(logging.WARNING) # make explicit though this is the
default, currently

... more code...
... I'll show some of the context of how I'm using it..  reading an SDF
file here, and want to trap every message

        f_in = open_sdf(INPUT_FILE, 'rb')
        # please don't change the molecule while reading it in
        suppl = Chem.ForwardSDMolSupplier(f_in, sanitize=False,
removeHs=False, strictParsing=False)

        with StringIO() as log_stream:
            log_handler = logging.StreamHandler(log_stream)
            myLogger = logging.getLogger('rdkit')
            myLogger.addHandler(log_handler)

            # usually don't pull from a generator this way, but we're
trying to catch log messages for each molecule individually
            while True:
                try:
                    # Python 3
                    log_stream.truncate(0)
                    log_stream.seek(0)
                    curmol = next(suppl)
                except StopIteration:
                    break

... capture everything in the stream from reading the molecule with
log_stream.getvalue()
            re.sub(r'\[[0-9]{2}:[0-9]{2}:[0-9]{2}[^]]*\]', '',
log_stream.getvalue()) # remove the timestamps [12:14:19] (maybe could turn
them off?)

... after closing SDF file I'm removing the handler
        # remove our log handler
        myLogger.handlers.clear()


On Thu, Feb 1, 2024 at 12:49 PM David Cosgrove <dav...@gm...>
wrote:

> Hi,
> I'd like to be able to redirect the various logging streams to files from
> within the code.  I know that I can turn them off:
>
> RDLogger.DisableLog('rdApp.*')
>
> but that's more extreme than I want.
> I have found the function RDLogger.AttachFileToLog() but can't work out
> how to use it.  The naive
>
> RDLogger.AttachFileToLog('rdApp.*', 'logging.file', 1)
>
> didn't produce a file anywhere I could see.  I have not been able to find
> an example of its use.
>
> find . -name \*.py -exec grep AttachFileToLog {} \; -print
>
> from the top of the source tree produces
>
> from rdkit.rdBase import AttachFileToLog, DisableLog, EnableLog, LogMessage
> ./rdkit/RDLogger.py
>
> but the functions don't seem to be used within that file.
>
> Any pointers gratefully received.
> Dave
>
>
> --
> David Cosgrove
> Freelance computational chemistry and chemoinformatics developer
> http://cozchemix.co.uk
>
> _______________________________________________
> Rdkit-discuss mailing list
> Rdk...@li...
> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>


-- 
Regards,
     Joel

----
*Joel L. Duerksen     *jo...@d2...
*Innovative Machine Learning and Data Science Solutions*

[Rdkit-discuss] Redirect error messages to a file in Python?

[David C. <dav...@gm...>]

Hi,
I'd like to be able to redirect the various logging streams to files from
within the code.  I know that I can turn them off:

RDLogger.DisableLog('rdApp.*')

but that's more extreme than I want.
I have found the function RDLogger.AttachFileToLog() but can't work out how
to use it.  The naive

RDLogger.AttachFileToLog('rdApp.*', 'logging.file', 1)

didn't produce a file anywhere I could see.  I have not been able to find
an example of its use.

find . -name \*.py -exec grep AttachFileToLog {} \; -print

from the top of the source tree produces

from rdkit.rdBase import AttachFileToLog, DisableLog, EnableLog, LogMessage
./rdkit/RDLogger.py

but the functions don't seem to be used within that file.

Any pointers gratefully received.
Dave


-- 
David Cosgrove
Freelance computational chemistry and chemoinformatics developer
http://cozchemix.co.uk

Re: [Rdkit-discuss] V2000 to V3000 enhanced stereo question

[Tomkinson, N. <nic...@as...>]

Thanks for that Greg.

Nick


From: Greg Landrum <gre...@gm...>
Sent: Wednesday, January 31, 2024 2:48 PM
To: Tomkinson, Nicholas <nic...@as...>
Cc: rdk...@li...
Subject: Re: [Rdkit-discuss] V2000 to V3000 enhanced stereo question

Thanks for that example Nick.
We can't handle this automatically since there are multiple interpretations of what the chiral flag means, but I think some relatively straightforward post-processing can do what you're looking for.
https://gist.github.com/greglandrum/f85097a8489ba4a5825b0981b1fd2408<https://gist.github.com/greglandrum/f85097a8489ba4a5825b0981b1fd2408>

If people think it's useful, this is something which we could add to the RDKit itself.

-greg



On Wed, Jan 31, 2024 at 2:53 PM Tomkinson, Nicholas <nic...@as...<mailto:nic...@as...>> wrote:
Hi Greg – sure. So -

[cid:image001.png@01DA5458.9B7BD490]

If I have a V2000 with or without the chiral flag:


  ACCLDraw01312413482D

  8  8  0  0  1  0  0  0  0  0999 V2000
    4.6334   -6.5969    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.6563   -6.0064    0.0000 C   0  0  2  0  0  0  0  0  0  0  0  0
    6.6791   -6.5969    0.0000 N   0  0  3  0  0  0  0  0  0  0  0  0
    6.6791   -7.7781    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.6563   -8.3686    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6334   -7.7781    0.0000 C   0  0  1  0  0  0  0  0  0  0  0  0
    5.6563   -4.8257    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6109   -8.3684    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0  0  0  0
  3  2  1  0  0  0  0
  4  3  1  0  0  0  0
  5  4  1  0  0  0  0
  1  6  1  0  0  0  0
  6  5  1  0  0  0  0
  2  7  1  1  0  0  0
  6  8  1  1  0  0  0
M  END


  ACCLDraw01312413492D

  8  8  0  0  0  0  0  0  0  0999 V2000
    4.6334   -6.5969    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.6563   -6.0064    0.0000 C   0  0  2  0  0  0  0  0  0  0  0  0
    6.6791   -6.5969    0.0000 N   0  0  3  0  0  0  0  0  0  0  0  0
    6.6791   -7.7781    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.6563   -8.3686    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6334   -7.7781    0.0000 C   0  0  1  0  0  0  0  0  0  0  0  0
    5.6563   -4.8257    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6109   -8.3684    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0  0  0  0
  3  2  1  0  0  0  0
  4  3  1  0  0  0  0
  5  4  1  0  0  0  0
  1  6  1  0  0  0  0
  6  5  1  0  0  0  0
  2  7  1  1  0  0  0
  6  8  1  1  0  0  0
M  END


I’d expect the enhanced collections to be output in V3000 format. In this case the chiral flag is also set but that’s not a biggy for me. (I wish the chiral flag didn’t exist in V3000.)


  ACCLDraw01312413472D

  0  0  0     0  0            999 V3000
M  V30 BEGIN CTAB
M  V30 COUNTS 8 8 0 0 1
M  V30 BEGIN ATOM
M  V30 1 C 4.6334 -6.5969 0 0
M  V30 2 C 5.6563 -6.0064 0 0 CFG=2
M  V30 3 N 6.6791 -6.5969 0 0 CFG=3
M  V30 4 C 6.6791 -7.7781 0 0
M  V30 5 C 5.6563 -8.3686 0 0
M  V30 6 C 4.6334 -7.7781 0 0 CFG=1
M  V30 7 C 5.6563 -4.8257 0 0
M  V30 8 C 3.6109 -8.3684 0 0
M  V30 END ATOM
M  V30 BEGIN BOND
M  V30 1 1 1 2
M  V30 2 1 3 2
M  V30 3 1 4 3
M  V30 4 1 5 4
M  V30 5 1 1 6
M  V30 6 1 6 5
M  V30 7 1 2 7 CFG=1
M  V30 8 1 6 8 CFG=1
M  V30 END BOND
M  V30 BEGIN COLLECTION
M  V30 MDLV30/STEABS ATOMS=(2 2 6)
M  V30 END COLLECTION
M  V30 END CTAB
M  END


  ACCLDraw01312413492D

  0  0  0     0  0            999 V3000
M  V30 BEGIN CTAB
M  V30 COUNTS 8 8 0 0 0
M  V30 BEGIN ATOM
M  V30 1 C 4.6334 -6.5969 0 0
M  V30 2 C 5.6563 -6.0064 0 0 CFG=2
M  V30 3 N 6.6791 -6.5969 0 0 CFG=3
M  V30 4 C 6.6791 -7.7781 0 0
M  V30 5 C 5.6563 -8.3686 0 0
M  V30 6 C 4.6334 -7.7781 0 0 CFG=1
M  V30 7 C 5.6563 -4.8257 0 0
M  V30 8 C 3.6109 -8.3684 0 0
M  V30 END ATOM
M  V30 BEGIN BOND
M  V30 1 1 1 2
M  V30 2 1 3 2
M  V30 3 1 4 3
M  V30 4 1 5 4
M  V30 5 1 1 6
M  V30 6 1 6 5
M  V30 7 1 2 7 CFG=1
M  V30 8 1 6 8 CFG=1
M  V30 END BOND
M  V30 BEGIN COLLECTION
M  V30 MDLV30/STERAC1 ATOMS=(2 6 2)
M  V30 END COLLECTION
M  V30 END CTAB
M  END

Cheers

Nick



From: Greg Landrum <gre...@gm...<mailto:gre...@gm...>>
Sent: Wednesday, January 31, 2024 1:45 PM
To: Tomkinson, Nicholas <nic...@as...<mailto:nic...@as...>>
Cc: rdk...@li...<mailto:rdk...@li...>
Subject: Re: [Rdkit-discuss] V2000 to V3000 enhanced stereo question

Hi Nick,

Can you provide an example of exactly what you would like to have happen?

-greg


On Tue, Jan 30, 2024 at 5:46 PM Tomkinson, Nicholas <nic...@as...<mailto:nic...@as...>> wrote:
I am trying to convert a simple V2000 molfile with or without the chiral flag into a V3000 molfile but this does not create an enhanced stereo collection in the V3000 molfile. This is a requirement for another application that does not handle V2000/V3000 mixtures well. Is there anyway of forcing the writing of the enhanced collection in this context?

Thanks

Nick

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Re: [Rdkit-discuss] V2000 to V3000 enhanced stereo question

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

Thanks for that example Nick.
We can't handle this automatically since there are multiple interpretations
of what the chiral flag means, but I think some relatively straightforward
post-processing can do what you're looking for.
https://gist.github.com/greglandrum/f85097a8489ba4a5825b0981b1fd2408

If people think it's useful, this is something which we could add to the
RDKit itself.

-greg



On Wed, Jan 31, 2024 at 2:53 PM Tomkinson, Nicholas <
nic...@as...> wrote:

> Hi Greg – sure. So -
>
>
>
>
>
> If I have a V2000 with or without the chiral flag:
>
>
>
>
>
>   ACCLDraw01312413482D
>
>
>
>   8  8  0  0  1  0  0  0  0  0999 V2000
>
>     4.6334   -6.5969    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
>
>     5.6563   -6.0064    0.0000 C   0  0  2  0  0  0  0  0  0  0  0  0
>
>     6.6791   -6.5969    0.0000 N   0  0  3  0  0  0  0  0  0  0  0  0
>
>     6.6791   -7.7781    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
>
>     5.6563   -8.3686    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
>
>     4.6334   -7.7781    0.0000 C   0  0  1  0  0  0  0  0  0  0  0  0
>
>     5.6563   -4.8257    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
>
>     3.6109   -8.3684    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
>
>   1  2  1  0  0  0  0
>
>   3  2  1  0  0  0  0
>
>   4  3  1  0  0  0  0
>
>   5  4  1  0  0  0  0
>
>   1  6  1  0  0  0  0
>
>   6  5  1  0  0  0  0
>
>   2  7  1  1  0  0  0
>
>   6  8  1  1  0  0  0
>
> M  END
>
>
>
>
>
>   ACCLDraw01312413492D
>
>
>
>   8  8  0  0  0  0  0  0  0  0999 V2000
>
>     4.6334   -6.5969    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
>
>     5.6563   -6.0064    0.0000 C   0  0  2  0  0  0  0  0  0  0  0  0
>
>     6.6791   -6.5969    0.0000 N   0  0  3  0  0  0  0  0  0  0  0  0
>
>     6.6791   -7.7781    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
>
>     5.6563   -8.3686    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
>
>     4.6334   -7.7781    0.0000 C   0  0  1  0  0  0  0  0  0  0  0  0
>
>     5.6563   -4.8257    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
>
>     3.6109   -8.3684    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
>
>   1  2  1  0  0  0  0
>
>   3  2  1  0  0  0  0
>
>   4  3  1  0  0  0  0
>
>   5  4  1  0  0  0  0
>
>   1  6  1  0  0  0  0
>
>   6  5  1  0  0  0  0
>
>   2  7  1  1  0  0  0
>
>   6  8  1  1  0  0  0
>
> M  END
>
>
>
>
>
> I’d expect the enhanced collections to be output in V3000 format. In this
> case the chiral flag is also set but that’s not a biggy for me. (I wish the
> chiral flag didn’t exist in V3000.)
>
>
>
>
>
>   ACCLDraw01312413472D
>
>
>
>   0  0  0     0  0            999 V3000
>
> M  V30 BEGIN CTAB
>
> M  V30 COUNTS 8 8 0 0 1
>
> M  V30 BEGIN ATOM
>
> M  V30 1 C 4.6334 -6.5969 0 0
>
> M  V30 2 C 5.6563 -6.0064 0 0 CFG=2
>
> M  V30 3 N 6.6791 -6.5969 0 0 CFG=3
>
> M  V30 4 C 6.6791 -7.7781 0 0
>
> M  V30 5 C 5.6563 -8.3686 0 0
>
> M  V30 6 C 4.6334 -7.7781 0 0 CFG=1
>
> M  V30 7 C 5.6563 -4.8257 0 0
>
> M  V30 8 C 3.6109 -8.3684 0 0
>
> M  V30 END ATOM
>
> M  V30 BEGIN BOND
>
> M  V30 1 1 1 2
>
> M  V30 2 1 3 2
>
> M  V30 3 1 4 3
>
> M  V30 4 1 5 4
>
> M  V30 5 1 1 6
>
> M  V30 6 1 6 5
>
> M  V30 7 1 2 7 CFG=1
>
> M  V30 8 1 6 8 CFG=1
>
> M  V30 END BOND
>
> M  V30 BEGIN COLLECTION
>
> M  V30 MDLV30/STEABS ATOMS=(2 2 6)
>
> M  V30 END COLLECTION
>
> M  V30 END CTAB
>
> M  END
>
>
>
>
>
>   ACCLDraw01312413492D
>
>
>
>   0  0  0     0  0            999 V3000
>
> M  V30 BEGIN CTAB
>
> M  V30 COUNTS 8 8 0 0 0
>
> M  V30 BEGIN ATOM
>
> M  V30 1 C 4.6334 -6.5969 0 0
>
> M  V30 2 C 5.6563 -6.0064 0 0 CFG=2
>
> M  V30 3 N 6.6791 -6.5969 0 0 CFG=3
>
> M  V30 4 C 6.6791 -7.7781 0 0
>
> M  V30 5 C 5.6563 -8.3686 0 0
>
> M  V30 6 C 4.6334 -7.7781 0 0 CFG=1
>
> M  V30 7 C 5.6563 -4.8257 0 0
>
> M  V30 8 C 3.6109 -8.3684 0 0
>
> M  V30 END ATOM
>
> M  V30 BEGIN BOND
>
> M  V30 1 1 1 2
>
> M  V30 2 1 3 2
>
> M  V30 3 1 4 3
>
> M  V30 4 1 5 4
>
> M  V30 5 1 1 6
>
> M  V30 6 1 6 5
>
> M  V30 7 1 2 7 CFG=1
>
> M  V30 8 1 6 8 CFG=1
>
> M  V30 END BOND
>
> M  V30 BEGIN COLLECTION
>
> M  V30 MDLV30/STERAC1 ATOMS=(2 6 2)
>
> M  V30 END COLLECTION
>
> M  V30 END CTAB
>
> M  END
>
>
>
> Cheers
>
>
>
> Nick
>
>
>
>
>
>
>
> *From:* Greg Landrum <gre...@gm...>
> *Sent:* Wednesday, January 31, 2024 1:45 PM
> *To:* Tomkinson, Nicholas <nic...@as...>
> *Cc:* rdk...@li...
> *Subject:* Re: [Rdkit-discuss] V2000 to V3000 enhanced stereo question
>
>
>
> Hi Nick,
>
>
>
> Can you provide an example of exactly what you would like to have happen?
>
>
>
> -greg
>
>
>
>
>
> On Tue, Jan 30, 2024 at 5:46 PM Tomkinson, Nicholas <
> nic...@as...> wrote:
>
> I am trying to convert a simple V2000 molfile with or without the chiral
> flag into a V3000 molfile but this does not create an enhanced stereo
> collection in the V3000 molfile. This is a requirement for another
> application that does not handle V2000/V3000 mixtures well. Is there anyway
> of forcing the writing of the enhanced collection in this context?
>
>
>
> Thanks
>
>
>
> Nick
>
>
> ------------------------------
>
> AstraZeneca UK Limited is a company incorporated in England and Wales with
> registered number:03674842 and its registered office at 1 Francis Crick
> Avenue, Cambridge Biomedical Campus, Cambridge, CB2 0AA.
>
> This e-mail and its attachments are intended for the above named recipient
> only and may contain confidential and privileged information. If they have
> come to you in error, you must not copy or show them to anyone; instead,
> please reply to this e-mail, highlighting the error to the sender and then
> immediately delete the message. For information about how AstraZeneca UK
> Limited and its affiliates may process information, personal data and
> monitor communications, please see our privacy notice at
> www.astrazeneca.com
>
> _______________________________________________
> Rdkit-discuss mailing list
> Rdk...@li...
> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>
> ------------------------------
>
> AstraZeneca UK Limited is a company incorporated in England and Wales with
> registered number:03674842 and its registered office at 1 Francis Crick
> Avenue, Cambridge Biomedical Campus, Cambridge, CB2 0AA.
>
> This e-mail and its attachments are intended for the above named recipient
> only and may contain confidential and privileged information. If they have
> come to you in error, you must not copy or show them to anyone; instead,
> please reply to this e-mail, highlighting the error to the sender and then
> immediately delete the message. For information about how AstraZeneca UK
> Limited and its affiliates may process information, personal data and
> monitor communications, please see our privacy notice at
> www.astrazeneca.com
>

Re: [Rdkit-discuss] V2000 to V3000 enhanced stereo question

[Giovanni T. <gio...@gl...>]

Hello Nick,
We faced a (seemingly) related problem a while ago. In our case we were trying to convert V2000 CTABs to CXSMILES, and we were expecting that the V2000 chirality flag would translate to an enhanced stereo string in the CXSMILES.
That is not so, by design. See my question, and the answer it got, here: V2000 chiral flag does not seem to be read by Chem.MolFromMolBlock() * Issue #6062 * rdkit/rdkit * GitHub<https://github.com/rdkit/rdkit/issues/6062>

I imagine that the reason why the V2000 to V3000 conversion does not use the V2000 chirality flag is conceptually the same, but indeed worth checking.

FYI, the practical solution for our workflow was:

  *   create a function 'chiral_flag_from_molblock' that detects if a CTAB is V2000 or V3000; if V2000, reads the flag (by simple text parsing) and returns it (0 or 1), if V3000, returns -1
  *   create a function 'CTAB_to_CXSMILES' that calls the above; for V3000, the rdkit-generated CXSMILES is (or usually is) already correct; for V2000, if the flag is 1, the SMILES is identical to the CXSMILES; if the flag is 0, the function loops through all atoms, identifies those that have tetrahedral stereochemistry, and uses their indices to put together an '&1' enhanced stereo group string, which is then appended to the SMILES (as a V2000 CTAB with chirality flag 0 can only represent a racemic mixture where all configurations are inverted together, so it only needs one '&' group - of course with all the exceptions and issues you can imagine: meso stereoisomers or moieties, etc)

Probably not ideal, but lacking any suggestion or a better 'native' solution, that's what we went for, and it seems to have worked so far.
[I'll mention for completeness that we also run a further standardisation function on CXSMILES, which takes care of removing the enhanced stereo flags from meso moieties].

I hope this helps.

Regards

[cid:image001.png@01DA5433.970407E0]

[cid:image002.png@01DA5433.970407E0]<https://twitter.com/GalapagosGlobal> [cid:image003.png@01DA5433.970407E0] <https://www.linkedin.com/company/glpg>  [cid:image004.png@01DA5433.970407E0] <https://www.youtube.com/c/GalapagosGlobal>  [cid:image005.png@01DA5433.970407E0] <https://www.glpg.com/>
Giovanni Tricarico
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From: Tomkinson, Nicholas <nic...@as...>
Sent: Tuesday, January 30, 2024 5:28 PM
To: rdk...@li...
Subject: [Rdkit-discuss] V2000 to V3000 enhanced stereo question

Some people who received this message don't often get email from nic...@as...<mailto:nic...@as...>. Learn why this is important<https://aka.ms/LearnAboutSenderIdentification>
I am trying to convert a simple V2000 molfile with or without the chiral flag into a V3000 molfile but this does not create an enhanced stereo collection in the V3000 molfile. This is a requirement for another application that does not handle V2000/V3000 mixtures well. Is there anyway of forcing the writing of the enhanced collection in this context?

Thanks

Nick

________________________________
AstraZeneca UK Limited is a company incorporated in England and Wales with registered number:03674842 and its registered office at 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge, CB2 0AA.
This e-mail and its attachments are intended for the above named recipient only and may contain confidential and privileged information. If they have come to you in error, you must not copy or show them to anyone; instead, please reply to this e-mail, highlighting the error to the sender and then immediately delete the message. For information about how AstraZeneca UK Limited and its affiliates may process information, personal data and monitor communications, please see our privacy notice at www.astrazeneca.com<https://www.astrazeneca.com/>
This e-mail and its attachment(s) (if any) may contain confidential and/or proprietary information and is intended for its addressee(s) only. Any unauthorized use of the information contained herein (including, but not limited to, alteration, reproduction, communication, distribution or any other form of dissemination) is strictly prohibited. If you are not the intended addressee, please notify the originator promptly and delete this e-mail and its attachment(s) (if any) subsequently. Neither Galapagos nor any of its affiliates shall be liable for direct, special, indirect or consequential damages arising from alteration of the contents of this message (by a third party) or as a result of a virus being passed on.

Re: [Rdkit-discuss] V2000 to V3000 enhanced stereo question

[Tomkinson, N. <nic...@as...>]

Hi Greg – sure. So -

[cid:image001.png@01DA544C.50E20B90]

If I have a V2000 with or without the chiral flag:


  ACCLDraw01312413482D

  8  8  0  0  1  0  0  0  0  0999 V2000
    4.6334   -6.5969    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.6563   -6.0064    0.0000 C   0  0  2  0  0  0  0  0  0  0  0  0
    6.6791   -6.5969    0.0000 N   0  0  3  0  0  0  0  0  0  0  0  0
    6.6791   -7.7781    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.6563   -8.3686    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6334   -7.7781    0.0000 C   0  0  1  0  0  0  0  0  0  0  0  0
    5.6563   -4.8257    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6109   -8.3684    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0  0  0  0
  3  2  1  0  0  0  0
  4  3  1  0  0  0  0
  5  4  1  0  0  0  0
  1  6  1  0  0  0  0
  6  5  1  0  0  0  0
  2  7  1  1  0  0  0
  6  8  1  1  0  0  0
M  END


  ACCLDraw01312413492D

  8  8  0  0  0  0  0  0  0  0999 V2000
    4.6334   -6.5969    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.6563   -6.0064    0.0000 C   0  0  2  0  0  0  0  0  0  0  0  0
    6.6791   -6.5969    0.0000 N   0  0  3  0  0  0  0  0  0  0  0  0
    6.6791   -7.7781    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.6563   -8.3686    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6334   -7.7781    0.0000 C   0  0  1  0  0  0  0  0  0  0  0  0
    5.6563   -4.8257    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6109   -8.3684    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0  0  0  0
  3  2  1  0  0  0  0
  4  3  1  0  0  0  0
  5  4  1  0  0  0  0
  1  6  1  0  0  0  0
  6  5  1  0  0  0  0
  2  7  1  1  0  0  0
  6  8  1  1  0  0  0
M  END


I’d expect the enhanced collections to be output in V3000 format. In this case the chiral flag is also set but that’s not a biggy for me. (I wish the chiral flag didn’t exist in V3000.)


  ACCLDraw01312413472D

  0  0  0     0  0            999 V3000
M  V30 BEGIN CTAB
M  V30 COUNTS 8 8 0 0 1
M  V30 BEGIN ATOM
M  V30 1 C 4.6334 -6.5969 0 0
M  V30 2 C 5.6563 -6.0064 0 0 CFG=2
M  V30 3 N 6.6791 -6.5969 0 0 CFG=3
M  V30 4 C 6.6791 -7.7781 0 0
M  V30 5 C 5.6563 -8.3686 0 0
M  V30 6 C 4.6334 -7.7781 0 0 CFG=1
M  V30 7 C 5.6563 -4.8257 0 0
M  V30 8 C 3.6109 -8.3684 0 0
M  V30 END ATOM
M  V30 BEGIN BOND
M  V30 1 1 1 2
M  V30 2 1 3 2
M  V30 3 1 4 3
M  V30 4 1 5 4
M  V30 5 1 1 6
M  V30 6 1 6 5
M  V30 7 1 2 7 CFG=1
M  V30 8 1 6 8 CFG=1
M  V30 END BOND
M  V30 BEGIN COLLECTION
M  V30 MDLV30/STEABS ATOMS=(2 2 6)
M  V30 END COLLECTION
M  V30 END CTAB
M  END


  ACCLDraw01312413492D

  0  0  0     0  0            999 V3000
M  V30 BEGIN CTAB
M  V30 COUNTS 8 8 0 0 0
M  V30 BEGIN ATOM
M  V30 1 C 4.6334 -6.5969 0 0
M  V30 2 C 5.6563 -6.0064 0 0 CFG=2
M  V30 3 N 6.6791 -6.5969 0 0 CFG=3
M  V30 4 C 6.6791 -7.7781 0 0
M  V30 5 C 5.6563 -8.3686 0 0
M  V30 6 C 4.6334 -7.7781 0 0 CFG=1
M  V30 7 C 5.6563 -4.8257 0 0
M  V30 8 C 3.6109 -8.3684 0 0
M  V30 END ATOM
M  V30 BEGIN BOND
M  V30 1 1 1 2
M  V30 2 1 3 2
M  V30 3 1 4 3
M  V30 4 1 5 4
M  V30 5 1 1 6
M  V30 6 1 6 5
M  V30 7 1 2 7 CFG=1
M  V30 8 1 6 8 CFG=1
M  V30 END BOND
M  V30 BEGIN COLLECTION
M  V30 MDLV30/STERAC1 ATOMS=(2 6 2)
M  V30 END COLLECTION
M  V30 END CTAB
M  END

Cheers

Nick



From: Greg Landrum <gre...@gm...>
Sent: Wednesday, January 31, 2024 1:45 PM
To: Tomkinson, Nicholas <nic...@as...>
Cc: rdk...@li...
Subject: Re: [Rdkit-discuss] V2000 to V3000 enhanced stereo question

Hi Nick,

Can you provide an example of exactly what you would like to have happen?

-greg


On Tue, Jan 30, 2024 at 5:46 PM Tomkinson, Nicholas <nic...@as...<mailto:nic...@as...>> wrote:
I am trying to convert a simple V2000 molfile with or without the chiral flag into a V3000 molfile but this does not create an enhanced stereo collection in the V3000 molfile. This is a requirement for another application that does not handle V2000/V3000 mixtures well. Is there anyway of forcing the writing of the enhanced collection in this context?

Thanks

Nick

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Re: [Rdkit-discuss] V2000 to V3000 enhanced stereo question

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

Hi Nick,

Can you provide an example of exactly what you would like to have happen?

-greg


On Tue, Jan 30, 2024 at 5:46 PM Tomkinson, Nicholas <
nic...@as...> wrote:

> I am trying to convert a simple V2000 molfile with or without the chiral
> flag into a V3000 molfile but this does not create an enhanced stereo
> collection in the V3000 molfile. This is a requirement for another
> application that does not handle V2000/V3000 mixtures well. Is there anyway
> of forcing the writing of the enhanced collection in this context?
>
>
>
> Thanks
>
>
>
> Nick
>
>
> ------------------------------
>
> AstraZeneca UK Limited is a company incorporated in England and Wales with
> registered number:03674842 and its registered office at 1 Francis Crick
> Avenue, Cambridge Biomedical Campus, Cambridge, CB2 0AA.
>
> This e-mail and its attachments are intended for the above named recipient
> only and may contain confidential and privileged information. If they have
> come to you in error, you must not copy or show them to anyone; instead,
> please reply to this e-mail, highlighting the error to the sender and then
> immediately delete the message. For information about how AstraZeneca UK
> Limited and its affiliates may process information, personal data and
> monitor communications, please see our privacy notice at
> www.astrazeneca.com
> _______________________________________________
> Rdkit-discuss mailing list
> Rdk...@li...
> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>

Re: [Rdkit-discuss] V2000 to V3000 enhanced stereo question

[Tomkinson, N. <nic...@as...>]

Thanks Tricarico - I was afraid this might be the answer, but thanks for your suggestion. I'm not entirely sure I understand how adding an enhanced stereo collection reflecting the status of the chiral flag when going from V2000 to V3000 is a problem; it would be good to see some examples. I know the chiral flag is a nightmare in when reading V3000 but when reading V2000 if it's not set correctly then the file is broken and setting the enhanced collection doesn't make it more broken. It would be nice if creating an enhanced collection from the chiral flag (when reading V2000 only)  was available as an option.

Cheers

Nick


From: Giovanni Tricarico <gio...@gl...>
Sent: Wednesday, January 31, 2024 9:55 AM
To: Tomkinson, Nicholas <nic...@as...>; rdk...@li...
Subject: RE: V2000 to V3000 enhanced stereo question

Hello Nick,
We faced a (seemingly) related problem a while ago. In our case we were trying to convert V2000 CTABs to CXSMILES, and we were expecting that the V2000 chirality flag would translate to an enhanced stereo string in the CXSMILES.
That is not so, by design. See my question, and the answer it got, here: V2000 chiral flag does not seem to be read by Chem.MolFromMolBlock() * Issue #6062 * rdkit/rdkit * GitHub<https://github.com/rdkit/rdkit/issues/6062>

I imagine that the reason why the V2000 to V3000 conversion does not use the V2000 chirality flag is conceptually the same, but indeed worth checking.

FYI, the practical solution for our workflow was:

  *   create a function 'chiral_flag_from_molblock' that detects if a CTAB is V2000 or V3000; if V2000, reads the flag (by simple text parsing) and returns it (0 or 1), if V3000, returns -1
  *   create a function 'CTAB_to_CXSMILES' that calls the above; for V3000, the rdkit-generated CXSMILES is (or usually is) already correct; for V2000, if the flag is 1, the SMILES is identical to the CXSMILES; if the flag is 0, the function loops through all atoms, identifies those that have tetrahedral stereochemistry, and uses their indices to put together an '&1' enhanced stereo group string, which is then appended to the SMILES (as a V2000 CTAB with chirality flag 0 can only represent a racemic mixture where all configurations are inverted together, so it only needs one '&' group - of course with all the exceptions and issues you can imagine: meso stereoisomers or moieties, etc)

Probably not ideal, but lacking any suggestion or a better 'native' solution, that's what we went for, and it seems to have worked so far.
[I'll mention for completeness that we also run a further standardisation function on CXSMILES, which takes care of removing the enhanced stereo flags from meso moieties].

I hope this helps.

Regards

[cid:image001.png@01DA542E.D3A90830]

[cid:image002.png@01DA542E.D3A90830]<https://twitter.com/GalapagosGlobal> [cid:image003.png@01DA542E.D3A90830] <https://www.linkedin.com/company/glpg>  [cid:image004.png@01DA542E.D3A90830] <https://www.youtube.com/c/GalapagosGlobal>  [cid:image005.png@01DA542E.D3A90830] <https://www.glpg.com/>
Giovanni Tricarico
Principal Scientist Chemoinformatics
+32 15 6514 30<callto:+32%2015%206514%2030>
gio...@gl...<mailto:gio...@gl...>
Galapagos NV
Generaal De Wittelaan L11 A3
2800 Mechelen, Belgium













From: Tomkinson, Nicholas <nic...@as...<mailto:nic...@as...>>
Sent: Tuesday, January 30, 2024 5:28 PM
To: rdk...@li...<mailto:rdk...@li...>
Subject: [Rdkit-discuss] V2000 to V3000 enhanced stereo question

Some people who received this message don't often get email from nic...@as...<mailto:nic...@as...>. Learn why this is important<https://aka.ms/LearnAboutSenderIdentification>
I am trying to convert a simple V2000 molfile with or without the chiral flag into a V3000 molfile but this does not create an enhanced stereo collection in the V3000 molfile. This is a requirement for another application that does not handle V2000/V3000 mixtures well. Is there anyway of forcing the writing of the enhanced collection in this context?

Thanks

Nick

________________________________
AstraZeneca UK Limited is a company incorporated in England and Wales with registered number:03674842 and its registered office at 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge, CB2 0AA.
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________________________________

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This e-mail and its attachments are intended for the above named recipient only and may contain confidential and privileged information. If they have come to you in error, you must not copy or show them to anyone; instead, please reply to this e-mail, highlighting the error to the sender and then immediately delete the message. For information about how AstraZeneca UK Limited and its affiliates may process information, personal data and monitor communications, please see our privacy notice at www.astrazeneca.com<https://www.astrazeneca.com>

[Rdkit-discuss] V2000 to V3000 enhanced stereo question

[Tomkinson, N. <nic...@as...>]

I am trying to convert a simple V2000 molfile with or without the chiral flag into a V3000 molfile but this does not create an enhanced stereo collection in the V3000 molfile. This is a requirement for another application that does not handle V2000/V3000 mixtures well. Is there anyway of forcing the writing of the enhanced collection in this context?

Thanks

Nick

________________________________

AstraZeneca UK Limited is a company incorporated in England and Wales with registered number:03674842 and its registered office at 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge, CB2 0AA.

This e-mail and its attachments are intended for the above named recipient only and may contain confidential and privileged information. If they have come to you in error, you must not copy or show them to anyone; instead, please reply to this e-mail, highlighting the error to the sender and then immediately delete the message. For information about how AstraZeneca UK Limited and its affiliates may process information, personal data and monitor communications, please see our privacy notice at www.astrazeneca.com<https://www.astrazeneca.com>

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

[He, A. <he...@bu...>]

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)
```

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

[Emre A. <emr...@gm...>]

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)
```

[Rdkit-discuss] mmpdb 3.1

[Andrew D. <da...@da...>]

Hi everyone,

  We have released mmpdb 3.1, which you can get from https://github.com/rdkit/mmpdb .

mmpdb 3.0, released May 2023, merged three development tracks:

- create and query 1-cut med chem transformations as described in Awale et al., The Playbooks of Medicinal Chemistry Design Moves, J. Chem. Inf. Model. 2021, 61, 2, 729–742

- support indexing large datasets on a distributed cluster

- replace the hash-based fingerprint environment with a SMARTS/pseudo-SMILES description

Version 3.1 adds support for the 2- and 3-cut med chem transformations described by Awale et al.

There are also a few feature improvements, some performance tuning, and bug fixes. See the CHANGELOG for details.


				Andrew
				da...@da...

[Rdkit-discuss] Replace matched patterns with wildcards

[Marawan H. <mar...@ya...>]

Hi,
I am trying to use rdkit to replace matched SMARTS patterns in a molecule with a wildcard (*), and return a SMARTS string where the original molecule is an instance of this returned SMARTS string,
I tried the following:########from rdkit import Chem
def generate_modified_smarts(smiles, smarts_patterns, num_patterns_to_replace):    molecule = Chem.MolFromSmiles(smiles)    patterns_replaced = 0
    for smarts in smarts_patterns:        if patterns_replaced >= num_patterns_to_replace:            break
        pattern = Chem.MolFromSmarts(smarts)        while molecule.HasSubstructMatch(pattern) and patterns_replaced < num_patterns_to_replace:            match_indices = molecule.GetSubstructMatch(pattern)
            # Extract segments before and after the match            before_match, after_match = "", ""            if match_indices[0] > 0:                before_match = Chem.MolFragmentToSmarts(molecule, atomsToUse=list(range(match_indices[0])))            if match_indices[-1] < molecule.GetNumAtoms() - 1:                after_match = Chem.MolFragmentToSmarts(molecule, atomsToUse=list(range(match_indices[-1] + 1, molecule.GetNumAtoms())))
            # Combine parts with a wildcard            modified_smarts = before_match + '*' + after_match            molecule = Chem.MolFromSmarts(modified_smarts)            patterns_replaced += 1
    return Chem.MolToSmarts(molecule)

example_smiles = "CCOC1=C(C=C2C(=C1)N=CC(=C2NC3=CC(=C(C=C3)OCC4=CC=CC=N4)Cl)C#N)NC(=O)C=CCN(C)C"smarts_patterns = ["C=O", "C#N"]num_patterns_to_replace = 2
modified_smarts = generate_modified_smarts(example_smiles, smarts_patterns, num_patterns_to_replace)print(f"Modified molecule SMARTS pattern: {modified_smarts}")#######
While it seems to work for C=O, it does not for C#N and the connectivity is messed up for C#N, even if I use it alone, i.e. without the carbonyl. The matched patterns could be anywhere in the molecule and could be more complex than this, but I just tried some simple cases to see how robust is this approach. It worked for "CCO", but did not work when i tried "Cl".
I am wondering if this is something you can help with,

Marawan