[Rdkit-discuss] FindMolChiralCenters finds centers in achiral bicyclo systems
I noticed Chem.FindMolChiralCenters is finding one or two chiral centers in the
bicyclo systems below which I believe do not have any chiral centers.
import rdkit
print(rdkit.__version__)
m1 = Chem.MolFromSmiles("NC12CC(C2)C1") # bicyclo[1.1.1]pentan-1-amine
m2 = Chem.MolFromSmiles("N1(CC2)CCC2CC1") # quinuclidine
m3 = Chem.MolFromSmiles("C1(C2)CCC2CC1") # bicyclo[2.2.1]heptane
print(Chem.FindMolChiralCenters(m1,includeUnassigned=True,useLegacyImplementation=False))
print(Chem.FindMolChiralCenters(m2,includeUnassigned=True,useLegacyImplementation=False))
print(Chem.FindMolChiralCenters(m3,includeUnassigned=True,useLegacyImplementation=False))
2021.03.4
[(1, '?'), (3, '?')]
[(0, '?'), (5, '?')]
[(0, '?')]
[(0, '?')]
Sean Murphy
Takeda San Diego
Medicinal Chemistry
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Re: [Rdkit-discuss] Parsing a PDB file with atoms that are too close, causing bad bond
On 27/09/2021 19:22, Lewis Martin wrote:
Very interesting - thank you Francois! PDB re-do does the trick:
import requests
from rdkit import Chem
def getPDB(code):
out =
requests.get(f'https://pdb-redo.eu/db/{code}/{code}_final.pdb')
return out.content
pdb_string = getPDB('3udn')
Chem.MolFromPDBBlock(pdb_string)
I think this solves it for me, but if anyone knows how to infer
correct bonding information without relying on distances, I'd love to
hear it too! So far I've noticed that Parmed and PDBFixer infer
correct bonds, but they don't determine bond orders, so it's difficult
to port the molecule into RDKit.
I just remember one paper; it might give you an entry point into the
scientific literature:
Determination of molecular topology and atomic hybridization states from
heavy atom coordinates
Elaine C. Meng, Richard A. Lewis
https://doi.org/10.1002/jcc.540120716
Regards,
F.
Cheers
Lewis
On Mon, Sep 27, 2021 at 5:55 PM Francois Berenger
wrote:
Hi Lewis,
Just an idea: you might try to load your PDB in UCSF Chimera, then
save it as a mol2 or sdf file.
Then, try to read this sdf file from rdkit.
Another idea: try to get your pdb file through the pdbredo service.
https://pdb-redo.eu/
They might have fixed a few things; maybe this PDB will read better
in
rdkit.
Regards,
F.
On 26/09/2021 17:02, Lewis Martin wrote:
Hi RDKit,
While parsing proteins from the PBD with RDKit, I've come across
situations where the distance-based bond determination leads to
'incorrect' bonds between atoms that are erroneously too close
together. PDB files have no bond information, so it's not really
'incorrect' (rather the model coordinates are off), but the bonds
are
nonphysical - and it means the Mol objects won't sanitize.
Here's an example:
import requests
from io import BytesIO
import gzip
from rdkit import Chem
def getPDB(code):
out =
requests.get(f'https://files.rcsb.org/download/{code}.pdb1.gz [1]
[1]')
binary_stream = BytesIO(out.content)
return gzip.open(binary_stream).read()
pdb_string = getPDB('3udn')
Chem.MolFromPDBBlock(pdb_string)
Error is:
RDKit ERROR: [22:38:21] Explicit valence for atom # 573 O, 3, is
greater than permitted
This is caused by the threonine 72 sidechain being too close to
the
TYR71 backbone carbonyl oxygen (this can be visualized at
https://www.rcsb.org/3d-view/3UDN?preset=ligandInteraction=09B
,
TYR71 is near the ligand).
Does anyone know how to avoid this to create a Chem.Mol? I've
tried
using Parmed and PDBFixer, since they use residue templates to
generate the correct bonding topology, but they don't write CONECT
records or SDFs, so the bonds are still lost to RDKit.
Thanks for your time!
Lewis
PS - why not just use PDBFixer? I'm trying to calculate atom
invariants using RDKit's morgan fingerprinter implementation, so
ultimately I want a sanitized Mol object
Links:
--
[1] https://files.rcsb.org/download/%7Bcode%7D.pdb1.gz
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[Rdkit-discuss] MFP question about similar substructures and feature reduction
Hello, Apologies. this is a very basic question: If I am converting many ligands into morgan fingerprints, could I theoretically stack the bit representations on top of each other to get the same features represented across ligands? For example is the below representation correct? | sample | feature1 | feature2 | feature3 | |: |::|::|-:| | 1 | bit 1| bit 2| bit 3| | 2 | bit 1| bit 2| bit 3| | 3 | bit 1| bit 2| bit 3| So basically is feature 1, 2, 3 etc always one type of substructure no matter what the input molecule is? What happens if the 2048 bits or substructures predesignated in rdkit do not contain a new substructure in a molecule we are evaluating? Any advice on how to reduce features and then use that reduced feature list for new molecules after training a model would also be appreciated. How would the model only extract the reduced bits for a new ligand if I remove low variance bits from the training set for example? ___ Rdkit-discuss mailing list Rdkit-discuss@lists.sourceforge.net https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
Re: [Rdkit-discuss] validating stereochemistry
Thanks Brian. Didn't know that existed! Very useful. As you mention, it is a lot slower to do the check. Tim On Mon, Sep 27, 2021 at 1:30 PM Brian Cole wrote: > Good Morning Tim, > > The RDKit EnumerateStereoisomers function accomplishes this through the > ‘tryEmbedding’ flag: > https://github.com/rdkit/rdkit/blob/d20e5cadc81bf6c7b4e590124866f178f2f2fe28/rdkit/Chem/EnumerateStereoisomers.py#L8 > > It attempts to generate a 3D conformer for the given stereo configuration > and fails the configuration if the conformer isn’t reasonable. Not fast, > but it is reliable. > > -Brian > > > On Sep 27, 2021, at 8:06 AM, Tim Dudgeon wrote: > > > I have Python code to enumerate undefined chiral centres in a molecule. > Mostly this works fine, but for some constrained structures this can > generate stereochemistry that makes no sense. For > instance consider NC1CC2CCC1C2: > <#1 (2).png> > > > These two make sense: > <#2.png> > > <#3.png> > > > But these two don't: > <#5.png> > > <#4.png> > > > Is there a way to filter out the invalid ones? > > Thanks > Tim > ___ > Rdkit-discuss mailing list > Rdkit-discuss@lists.sourceforge.net > https://lists.sourceforge.net/lists/listinfo/rdkit-discuss > > ___ Rdkit-discuss mailing list Rdkit-discuss@lists.sourceforge.net https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
Re: [Rdkit-discuss] validating stereochemistry
Hello, very interesting. I think it is worth raising a related point regarding the representation of stereochemistry for such types of molecules, because it’s important not only to validate them, but to interpret them correctly, too. See this document: http://publications.iupac.org/pac/2006/pdf/7810x1897.pdf Page 1926, at the bottom, shows this: [cid:image006.png@01D7B3AF.AB916440] The question is: when you submit to rdkit a molecule with the wedge pointing to the exocyclic H, is the stereochemistry correctly interpreted by rdkit (regardless of the conformational possibility of it existing or not)? Using Biovia Draw, with the various possibilities (I changed a bit the molecule in the OP to make the CIP assignment more obvious), you see that indeed it’s not as easy as it seems: [cid:image007.jpg@01D7B3B1.6B11C930] If the 6-membered ring bonds are all on the plane, what does an up wedge to the top H atom mean? Presumably, that the bond ‘in the middle’ of the ring, the one going from C to NH, is below the plane. In that case, the stereochemistry for the top C is R. And as you can see, the software ‘gets it wrong’ when using the exocyclic wedge. Perhaps it would be interesting to know what rdkit makes of a molecule like the first one on the left. Does it ‘read’ the stereochemistry correctly? brg Giovanni From: Tim Dudgeon Sent: 27 September 2021 14:04 To: RDKit Discuss Subject: [Rdkit-discuss] validating stereochemistry *** CAUTION : External e-mail *** I have Python code to enumerate undefined chiral centres in a molecule. Mostly this works fine, but for some constrained structures this can generate stereochemistry that makes no sense. For instance consider NC1CC2CCC1C2: [cid:image001.png@01D7B3AF.4C33C970] These two make sense: [cid:image002.png@01D7B3AF.4C33C970] [cid:image003.png@01D7B3AF.4C33C970] But these two don't: [cid:image004.png@01D7B3AF.4C33C970] [cid:image005.png@01D7B3AF.4C33C970] Is there a way to filter out the invalid ones? Thanks Tim ___ Rdkit-discuss mailing list Rdkit-discuss@lists.sourceforge.net https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
Re: [Rdkit-discuss] Parsing a PDB file with atoms that are too close, causing bad bond
Hi Lewis,
You can try to use PreparePDBMol in oddt
https://github.com/oddt/oddt/blob/master/oddt/toolkits/extras/rdkit/fixer.py#L623-L669
that we used in PLEC model training and PDBFixer didn't worked for us
either. Note that as soon as you have correct bonding you can disable
automatic bonding in RDKit using proximityBonding=False.
Pozdrawiam, | Best regards,
Maciek Wójcikowski
mac...@wojcikowski.pl
pon., 27 wrz 2021 o 12:25 Lewis Martin
napisał(a):
> Very interesting - thank you Francois! PDB re-do does the trick:
>
>
>
>
>
>
>
>
>
> *import requestsfrom rdkit import Chemdef getPDB(code):out =
> requests.get(f'https://pdb-redo.eu/db/{code}/{code}_final.pdb
> ')return
> out.contentpdb_string = getPDB('3udn')Chem.MolFromPDBBlock(pdb_string)*
>
> I think this solves it for me, but if anyone knows how to infer correct
> bonding information without relying on distances, I'd love to hear it too!
> So far I've noticed that Parmed and PDBFixer infer correct bonds, but they
> don't determine bond orders, so it's difficult to port the molecule into
> RDKit.
>
> Cheers
> Lewis
>
>
>
> On Mon, Sep 27, 2021 at 5:55 PM Francois Berenger
> wrote:
>
>> Hi Lewis,
>>
>> Just an idea: you might try to load your PDB in UCSF Chimera, then
>> save it as a mol2 or sdf file.
>> Then, try to read this sdf file from rdkit.
>>
>> Another idea: try to get your pdb file through the pdbredo service.
>> https://pdb-redo.eu/
>> They might have fixed a few things; maybe this PDB will read better in
>> rdkit.
>>
>> Regards,
>> F.
>>
>> On 26/09/2021 17:02, Lewis Martin wrote:
>> > Hi RDKit,
>> > While parsing proteins from the PBD with RDKit, I've come across
>> > situations where the distance-based bond determination leads to
>> > 'incorrect' bonds between atoms that are erroneously too close
>> > together. PDB files have no bond information, so it's not really
>> > 'incorrect' (rather the model coordinates are off), but the bonds are
>> > nonphysical - and it means the Mol objects won't sanitize.
>> >
>> > Here's an example:
>> >
>> > import requests
>> > from io import BytesIO
>> > import gzip
>> > from rdkit import Chem
>> >
>> > def getPDB(code):
>> > out =
>> > requests.get(f'https://files.rcsb.org/download/{code}.pdb1.gz [1]')
>> > binary_stream = BytesIO(out.content)
>> > return gzip.open(binary_stream).read()
>> >
>> > pdb_string = getPDB('3udn')
>> > Chem.MolFromPDBBlock(pdb_string)
>> >
>> > Error is:
>> >
>> > RDKit ERROR: [22:38:21] Explicit valence for atom # 573 O, 3, is
>> > greater than permitted
>> >
>> > This is caused by the threonine 72 sidechain being too close to the
>> > TYR71 backbone carbonyl oxygen (this can be visualized at
>> > https://www.rcsb.org/3d-view/3UDN?preset=ligandInteraction=09B ,
>> > TYR71 is near the ligand).
>> >
>> > Does anyone know how to avoid this to create a Chem.Mol? I've tried
>> > using Parmed and PDBFixer, since they use residue templates to
>> > generate the correct bonding topology, but they don't write CONECT
>> > records or SDFs, so the bonds are still lost to RDKit.
>> >
>> > Thanks for your time!
>> > Lewis
>> > PS - why not just use PDBFixer? I'm trying to calculate atom
>> > invariants using RDKit's morgan fingerprinter implementation, so
>> > ultimately I want a sanitized Mol object
>> >
>> > Links:
>> > --
>> > [1] https://files.rcsb.org/download/%7Bcode%7D.pdb1.gz
>> > ___
>> > Rdkit-discuss mailing list
>> > Rdkit-discuss@lists.sourceforge.net
>> > https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>>
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Re: [Rdkit-discuss] validating stereochemistry
Good Morning Tim, The RDKit EnumerateStereoisomers function accomplishes this through the ‘tryEmbedding’ flag: https://github.com/rdkit/rdkit/blob/d20e5cadc81bf6c7b4e590124866f178f2f2fe28/rdkit/Chem/EnumerateStereoisomers.py#L8 It attempts to generate a 3D conformer for the given stereo configuration and fails the configuration if the conformer isn’t reasonable. Not fast, but it is reliable. -Brian > > On Sep 27, 2021, at 8:06 AM, Tim Dudgeon wrote: > > > I have Python code to enumerate undefined chiral centres in a molecule. > Mostly this works fine, but for some constrained structures this can generate > stereochemistry that makes no sense. For instance consider NC1CC2CCC1C2: > <#1 (2).png> > > > These two make sense: > <#2.png> > > <#3.png> > > > But these two don't: > <#5.png> > > <#4.png> > > > Is there a way to filter out the invalid ones? > > Thanks > Tim > ___ > Rdkit-discuss mailing list > Rdkit-discuss@lists.sourceforge.net > https://lists.sourceforge.net/lists/listinfo/rdkit-discuss ___ Rdkit-discuss mailing list Rdkit-discuss@lists.sourceforge.net https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
[Rdkit-discuss] validating stereochemistry
I have Python code to enumerate undefined chiral centres in a molecule. Mostly this works fine, but for some constrained structures this can generate stereochemistry that makes no sense. For instance consider NC1CC2CCC1C2: [image: #1 (2).png] These two make sense: [image: #2.png] [image: #3.png] But these two don't: [image: #5.png] [image: #4.png] Is there a way to filter out the invalid ones? Thanks Tim ___ Rdkit-discuss mailing list Rdkit-discuss@lists.sourceforge.net https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
Re: [Rdkit-discuss] Parsing a PDB file with atoms that are too close, causing bad bond
Very interesting - thank you Francois! PDB re-do does the trick:
*import requestsfrom rdkit import Chemdef getPDB(code):out =
requests.get(f'https://pdb-redo.eu/db/{code}/{code}_final.pdb
')return
out.contentpdb_string = getPDB('3udn')Chem.MolFromPDBBlock(pdb_string)*
I think this solves it for me, but if anyone knows how to infer correct
bonding information without relying on distances, I'd love to hear it too!
So far I've noticed that Parmed and PDBFixer infer correct bonds, but they
don't determine bond orders, so it's difficult to port the molecule into
RDKit.
Cheers
Lewis
On Mon, Sep 27, 2021 at 5:55 PM Francois Berenger wrote:
> Hi Lewis,
>
> Just an idea: you might try to load your PDB in UCSF Chimera, then
> save it as a mol2 or sdf file.
> Then, try to read this sdf file from rdkit.
>
> Another idea: try to get your pdb file through the pdbredo service.
> https://pdb-redo.eu/
> They might have fixed a few things; maybe this PDB will read better in
> rdkit.
>
> Regards,
> F.
>
> On 26/09/2021 17:02, Lewis Martin wrote:
> > Hi RDKit,
> > While parsing proteins from the PBD with RDKit, I've come across
> > situations where the distance-based bond determination leads to
> > 'incorrect' bonds between atoms that are erroneously too close
> > together. PDB files have no bond information, so it's not really
> > 'incorrect' (rather the model coordinates are off), but the bonds are
> > nonphysical - and it means the Mol objects won't sanitize.
> >
> > Here's an example:
> >
> > import requests
> > from io import BytesIO
> > import gzip
> > from rdkit import Chem
> >
> > def getPDB(code):
> > out =
> > requests.get(f'https://files.rcsb.org/download/{code}.pdb1.gz [1]')
> > binary_stream = BytesIO(out.content)
> > return gzip.open(binary_stream).read()
> >
> > pdb_string = getPDB('3udn')
> > Chem.MolFromPDBBlock(pdb_string)
> >
> > Error is:
> >
> > RDKit ERROR: [22:38:21] Explicit valence for atom # 573 O, 3, is
> > greater than permitted
> >
> > This is caused by the threonine 72 sidechain being too close to the
> > TYR71 backbone carbonyl oxygen (this can be visualized at
> > https://www.rcsb.org/3d-view/3UDN?preset=ligandInteraction=09B ,
> > TYR71 is near the ligand).
> >
> > Does anyone know how to avoid this to create a Chem.Mol? I've tried
> > using Parmed and PDBFixer, since they use residue templates to
> > generate the correct bonding topology, but they don't write CONECT
> > records or SDFs, so the bonds are still lost to RDKit.
> >
> > Thanks for your time!
> > Lewis
> > PS - why not just use PDBFixer? I'm trying to calculate atom
> > invariants using RDKit's morgan fingerprinter implementation, so
> > ultimately I want a sanitized Mol object
> >
> > Links:
> > --
> > [1] https://files.rcsb.org/download/%7Bcode%7D.pdb1.gz
> > ___
> > Rdkit-discuss mailing list
> > Rdkit-discuss@lists.sourceforge.net
> > https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>
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Re: [Rdkit-discuss] Parsing a PDB file with atoms that are too close, causing bad bond
Hi Lewis,
Just an idea: you might try to load your PDB in UCSF Chimera, then
save it as a mol2 or sdf file.
Then, try to read this sdf file from rdkit.
Another idea: try to get your pdb file through the pdbredo service.
https://pdb-redo.eu/
They might have fixed a few things; maybe this PDB will read better in
rdkit.
Regards,
F.
On 26/09/2021 17:02, Lewis Martin wrote:
Hi RDKit,
While parsing proteins from the PBD with RDKit, I've come across
situations where the distance-based bond determination leads to
'incorrect' bonds between atoms that are erroneously too close
together. PDB files have no bond information, so it's not really
'incorrect' (rather the model coordinates are off), but the bonds are
nonphysical - and it means the Mol objects won't sanitize.
Here's an example:
import requests
from io import BytesIO
import gzip
from rdkit import Chem
def getPDB(code):
out =
requests.get(f'https://files.rcsb.org/download/{code}.pdb1.gz [1]')
binary_stream = BytesIO(out.content)
return gzip.open(binary_stream).read()
pdb_string = getPDB('3udn')
Chem.MolFromPDBBlock(pdb_string)
Error is:
RDKit ERROR: [22:38:21] Explicit valence for atom # 573 O, 3, is
greater than permitted
This is caused by the threonine 72 sidechain being too close to the
TYR71 backbone carbonyl oxygen (this can be visualized at
https://www.rcsb.org/3d-view/3UDN?preset=ligandInteraction=09B ,
TYR71 is near the ligand).
Does anyone know how to avoid this to create a Chem.Mol? I've tried
using Parmed and PDBFixer, since they use residue templates to
generate the correct bonding topology, but they don't write CONECT
records or SDFs, so the bonds are still lost to RDKit.
Thanks for your time!
Lewis
PS - why not just use PDBFixer? I'm trying to calculate atom
invariants using RDKit's morgan fingerprinter implementation, so
ultimately I want a sanitized Mol object
Links:
--
[1] https://files.rcsb.org/download/%7Bcode%7D.pdb1.gz
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