> It would be great if you (or your student) could create a github issue
for this, I will go ahead and take a look.
I will, thanks for looking into this.
On Thu, 15 Nov 2018 at 06:35, Greg Landrum <greg.land...@gmail.com> wrote:
> Hi JP,
>
> I am able to reproduce this.
> It's not directly connected to the standardization itself, since a
> standardized molecule works fine with the embedding:
>
> In [8]: omol = Chem.MolFromSmiles('C1=NN(C2=NC=NC(=O)[C@@H]21)[C@H]3[C@
> @H]([C@@H]([C@H](O3)CO)O)O')
>
> In [11]: nmol = rdMolStandardize.Cleanup(omol)
> [06:27:57] Initializing MetalDisconnector
> [06:27:57] Running MetalDisconnector
> [06:27:57] Initializing Normalizer
> [06:27:57] Running Normalizer
>
> In [12]: nomh = Chem.AddHs(nmol)
>
> In [13]: AllChem.EmbedMolecule(nomh)
> Out[13]: 0
>
>
> The actual problem is connected to the way the RDKit interprets the smiles
> that it generates for the input molecule (no standardization required):
>
> In [14]: omol = Chem.MolFromSmiles('C1=NN(C2=NC=NC(=O)[C@@H]21)[C@H]3[C@
> @H]([C@@H]([C@H](O3)CO)O)O')
>
> In [15]: smi = Chem.MolToSmiles(omol)
>
> In [16]: nmol = Chem.MolFromSmiles(smi)
>
> In [17]: hnmol = Chem.AddHs(nmol)
>
> In [18]: AllChem.EmbedMolecule(hnmol)
> Out[18]: -1
>
> In [19]: print(smi)
> O=C1N=CN=C2[C@H]1C=NN2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
>
>
> It would be great if you (or your student) could create a github issue for
> this, I will go ahead and take a look.
>
>
> Best,
> -greg
>
>
>
>
> On Wed, Nov 14, 2018 at 4:17 PM JP <j...@javaclass.co.uk> wrote:
>
>> Dear all,
>>
>> Using the latest/greatest 2018.09.1.
>>
>> I have an MSc student who is working on some targets in DUDE.
>>
>> If we take some specific molecules from there (e.g. "C1=NN(C2=NC=NC(=O)[C@
>> @H]21)[C@H]3[C@@H]([C@@H]([C@H](O3)CO)O)O"), sanitize them using r
>> dMolStandardize.StandardizeSmiles(smiles), and we then generate
>> conformers (with EmbedMultipleConfs and ETKDGv2) -- the conformer
>> generation step hangs. If we omit the sanitization step, conf. gen. works
>> fine as expected.
>>
>> Any clues as to what may be causing this? My bet in the above example is
>> something to do with chirality, i.e. [C@@H]. Any hint on a possible
>> solution?
>>
>> I'd also like to thank whoever it was who worked on integrating the
>> cleaning code (molvs) into RDKit. This is such a critical, common task -
>> great to have something out of the box to do it.
>>
>> We have an example jupyter notebook which highlights the problem here:
>> https://nbviewer.jupyter.org/gist/jp-um/528a300f6b46251377f3129576b61616
>>
>> Also, a list of other molecules which exhibit this same behaviour (just
>> the ones we came across, as we only looked at a small subset of DUDE
>> targets):
>>
>> Adenosine A2a receptor (GPCR)/ 28499( C1=CC2=c3nn/c(=N\N=C\[C@
>> @H]4C=CC=N4)[nH]c3=N[C@@H]2C=C1 )
>> Adenosine A2a receptor (GPCR)/ 9903(
>> [NH3+]NCC1=C(C(=O)[O-])[C@H]2C=Cc3cnc(Cl)cc3C2=N1
>> )
>> Adenosine A2a receptor (GPCR)/ 23728(
>> C1=C[C@@H]2N=CC=C2C=C1[C@@H]1N=CN=C1c1ccccc1
>> )
>> Progesterone Receptor/ 14194(
>> Cc1ccc(S(=O)(=O)C(Sc2ccccc2)=S=NC23CC4CC(CC(C4)C2)C3)cc1 )
>> Progesterone Receptor/ 14821( Cc1ccc(N2C(=O)[C@@H]3[C@@H]4C[C@H]5[C@H
>> ](O[C@@]2(C(C)C)[C@@H]53)[C@@H]4O)c(C)c1 )
>> Adenosine A2a receptor (GPCR)/ 4014(
>> CCc1ccc2c(c1)=C1N=[NH+]C(N/N=C/c3cc(OC)ccc3OC)=N[C@@H]1[NH+]=2 )
>> Progesterone Receptor/ 61(
>> CC(C)=C/C=C1\Oc2ccc(F)cc2-c2ccc3c(c21)C(C)=CC(C)(C)N3 )
>> Progesterone Receptor/ 67(
>> CC1=CC(C)(C)Nc2ccc3c(c21)C(=C1SCCCS1)Oc1ccc(F)cc1-3 )
>> Adenosine A2a receptor (GPCR)/ 29753(
>> Cc1ccc2c(c1)=C(CCN1C=C[C@H]3C(=CNc4nc(C)nn43)C1=O)C[NH+]=2
>> )
>> Adenosine A2a receptor (GPCR)/ 14471(
>> CCc1nn2c(c1-c1ccc(Cl)cc1)NC=C1C(=O)N(c3ncn[nH]3)C=C[C@@H]12 )
>> Adenosine A2a receptor (GPCR)/ 2411(
>> Cc1ccc2c(c1)=C1N=NC(N/N=C/c3cc(O)c(O)c(Br)c3)=[NH+][C@H]1[NH+]=2 )
>> HIVPR/ 21585(
>> O=[N+]([O-])c1ccc(N/N=C2/c3cc(Cl)ccc3N3c4ccccc4[C@@H]2N3c2ccccc2)c([N+](=O)[O-])c1
>> )
>> Adenosine A2a receptor (GPCR)/ 13221(
>> Cc1nn2c(c1-c1ccc(F)cc1)NC=C1C(=O)N(c3ncn[nH]3)C=C[C@H]12 )
>> Leukotriene A4 hydrolase (Protease)/ 8094( C[C@@H]([NH3+])[C@@H]1[C@H
>> ]2CC[C@H]3C[C@H](C2)C[C@@H]31 )
>> Leukotriene A4 hydrolase (Protease)/ 4803( CC1=N[C@@H]2C=C(OC[C@
>> @H]3CCN(C(=O)OC(C)(C)C)C3)C=C[C@H]2S1 )
>> Adenosine A2a receptor (GPCR)/ 8106(
>> O=CC1=CN=C2C=CC(c3cccc([N+](=O)[O-])c3)=C[C@H]12 )
>> Thymidine kinase/ 2696( CC(=O)O[C@H]1CC[C@@]2(COS(C)(=O)=O)[C@@H]3CC[C@
>> ]4(C)C5=C(O)C(=O)CO[C@@]4(CC5)[C@@H]3CC[C@]2(O)C1 )
>> Adenosine A2a receptor (GPCR)/ 5075(
>> Cc1ccc2c(c1)=C1N=[NH+]C(N/N=C/c3cc(Br)c(O)c(O)c3Br)=N[C@@H]1[NH+]=2 )
>> Adenosine A2a receptor (GPCR)/ 22643( COc1cc([N+](=O)[O-])ccc1NC(=O)[C@
>> @H]1[C@@H]2C[C@@H]3OC(=O)[C@@H]1[C@@H]3C2 )
>> Progesterone Receptor/ 182(
>> CC1=CC(C)(C)Nc2ccc3c(c21)/C(=C/C1CCCCC1)Oc1ccc(F)cc1-3 )
>>
>> Many thanks for your attention, looking forward to hear any insights
>> about this issue.
>>
>> JP
>> _______________________________________________
>> Rdkit-discuss mailing list
>> Rdkit-discuss@lists.sourceforge.net
>> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>>
>
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