OpenEye bond stereochemistry assumptions broken from ChEBI

Open adalke opened this issue 4 years ago • 0 comments

Following on https://github.com/openforcefield/openff-toolkit/issues/1008 , I processed 45,043 records from ChEBI to identify all those records where OEChem bond stereochemistry assumptions fail, when read by RDKitToolkitWrapper and converted to an OpenEye molecule object.

A @j-wags points out, this is not an expected use case.

For reference, these are:

CHEBI:15430 CHEBI:15436 CHEBI:27484 CHEBI:27609 CHEBI:28421
CHEBI:37447 CHEBI:44898 CHEBI:8337 CHEBI:9437 CHEBI:33084
CHEBI:33222 CHEBI:34921 CHEBI:36159 CHEBI:36160 CHEBI:36304
CHEBI:36779 CHEBI:37520 CHEBI:37521 CHEBI:37523 CHEBI:37524
CHEBI:38250 CHEBI:38256 CHEBI:38257 CHEBI:38258 CHEBI:41213
CHEBI:44085 CHEBI:47035 CHEBI:48398 CHEBI:48399 CHEBI:50285
CHEBI:50288 CHEBI:50289 CHEBI:50290 CHEBI:50291 CHEBI:51227
CHEBI:51228 CHEBI:51587 CHEBI:51591 CHEBI:51597 CHEBI:52183
CHEBI:52184 CHEBI:52189 CHEBI:52194 CHEBI:52197 CHEBI:52204
CHEBI:52207 CHEBI:52277 CHEBI:52278 CHEBI:52279 CHEBI:52542
CHEBI:52543 CHEBI:52544 CHEBI:52545 CHEBI:52546 CHEBI:52547
CHEBI:52548 CHEBI:52558 CHEBI:52563 CHEBI:57306 CHEBI:58742
CHEBI:58743 CHEBI:87674 CHEBI:131725 CHEBI:133626

Nearly all of them are porphyrins, like CHEBI:8337:

(Note: the SMILES, SDF, and depictions from ChEBI do not include stereochemistry.)

Many are cyclic tripyrroles, like CHEBI:51587

One oddly simple failure is octalene, CHEBI:33084

Here's a reproducible:

>>> from openff.toolkit import utils
>>> from urllib.request import urlopen
>>> rd_toolkit = utils.RDKitToolkitWrapper()
>>> f = urlopen("https://www.ebi.ac.uk/chebi/saveStructure.do?sdf=true&chebiId=33084&imageId=0")
>>> m = rd_toolkit.from_file_obj(f, "sdf")
>>> m
Traceback (most recent call last):
  ....
    "Programming error: OpenEye bond stereochemistry assumptions failed."
Exception: Programming error: OpenEye bond stereochemistry assumptions failed.

There are some failures with large cycles, in CHEBI:37523, CHEBI:37520, CHEBI:37521, and CHEBI:37524. The first is the smallest of these:

The last failing case is "new fuchsin(1+)", CHEBI:87674:

For the sake of depiction, I have extracted the <SMILES> entry of the SDF records for easy of pasting into something like CDK Depict. Again, note that the SMILES strings do not contain stereochemistry.

Cc1c(CCC(O)=O)c2cc3[nH]c(cc4nc(cc5[nH]c(cc1n2)c(C)c5C=C)c(C)c4C=C)c(C)c3CCC(O)=O CHEBI:15430
OC(=O)CCc1c(CC(O)=O)c2cc3[nH]c(cc4nc(cc5[nH]c(cc1n2)c(CCC(O)=O)c5CC(O)=O)c(CCC(O)=O)c4CC(O)=O)c(CCC(O)=O)c3CC(O)=O CHEBI:15436
OC(=O)CCc1c(CC(O)=O)c2cc3[nH]c(cc4nc(cc5[nH]c(cc1n2)c(CC(O)=O)c5CCC(O)=O)c(CC(O)=O)c4CCC(O)=O)c(CC(O)=O)c3CCC(O)=O CHEBI:27484
Cc1c(CCC(O)=O)c2cc3[nH]c(cc4nc(cc5[nH]c(cc1n2)c(C)c5CCC(O)=O)c(C)c4CCC(O)=O)c(C)c3CCC(O)=O CHEBI:27609
Cc1c(CCC(O)=O)c2cc3[nH]c(cc4nc(cc5[nH]c(cc1n2)c(CCC(O)=O)c5C)c(CCC(O)=O)c4C)c(CCC(O)=O)c3C CHEBI:28421
C[n+]1ccc(cc1)-c1c2ccc(n2)c(-c2cc[n+](C)cc2)c2ccc([nH]2)c(-c2cc[n+](C)cc2)c2ccc(n2)c(-c2cc[n+](C)cc2)c2ccc1[nH]2 CHEBI:37447
CCc1c(C)c2cc3[nH]c(cc4nc([C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@@H]4C)c4[C@@H](C(=O)OC)C(=O)c5c(C)c(cc1n2)[nH]c45)c(C)c3C=C CHEBI:44898
c1cc2cc3ccc(cc4ccc(cc5ccc(cc1n2)[nH]5)n4)[nH]3 CHEBI:8337
Oc1cccc(c1)-c1c2CCc(n2)c(-c2cccc(O)c2)c2ccc([nH]2)c(-c2cccc(O)c2)c2ccc(n2)c(-c2cccc(O)c2)c2ccc1[nH]2 CHEBI:9437
c1cccc2ccccccc2cc1 CHEBI:33084
c1cc2nc1cc1ccc(cc3ccc(cc4ccc2[nH]4)[nH]3)[nH]1 CHEBI:33222
c1ccc2c3nc(nc4[nH]c(nc5nc(nc6[nH]c(n3)c3ccccc63)c3ccccc53)c3ccccc43)c2c1 CHEBI:34921
Cc1c(CCC(O)=O)c2cc3[n-]c(cc4nc(cc5[n-]c(cc1n2)c(C)c5C=C)c(C)c4C=C)c(C)c3CCC(O)=O CHEBI:36159
COC(=O)CCc1c(C)c2cc3nc(cc4[nH]c(cc5nc(cc1[nH]2)c(CCC(O)=O)c5C)c(C)c4C=C)c(C)c3C=C CHEBI:36160
C1Cc2cc3ccc(cc4CCc(cc5ccc(cc1n2)[nH]5)n4)[nH]3 CHEBI:36304
c1cc2cc3ccc([nH]3)c3ccc(cc4ccc(cc5ccc(cc1n2)[nH]5)n4)[nH]3 CHEBI:36779
[H]c1c([H])c([H])c([H])c([H])c([H])c([H])c([H])c([H])c([H])c([H])c([H])c([H])c([H])c([H])c([H])c([H])c1[H] CHEBI:37520
[H]c1cc([H])cc([H])c([H])c([H])c([H])cc([H])cc([H])cc([H])c([H])c([H])c([H])c1 CHEBI:37521
[H]c1cc([H])c([H])c([H])cc([H])c([H])cc([H])c([H])c([H])cc1[H] CHEBI:37523
[H]c1cc([H])c([H])c([H])c([H])cc([H])cc([H])c([H])c([H])c([H])c1 CHEBI:37524
C1Cc2nc1cc1ccc(cc3ccc(cc4cc5CCc2c5[nH]4)n3)[nH]1 CHEBI:38250
[H]C(=O)c1c(CC)c2cc3[nH]c4c([C@@H](C(=O)OC)C(=O)c4c3C)c3nc(cc4[nH]c(cc1n2)c(C=C)c4C)[C@@H](C)[C@@H]3CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C CHEBI:38256
CCc1c(C)c2cc3[nH]c(cc4nc([C@@H](CCC(O)=O)[C@@H]4C)c4[C@@H](C(=O)OC)C(=O)c5c(C)c(cc1n2)[nH]c45)c(C)c3C=C CHEBI:38257
[H]C(=O)c1c(CC)c2cc3[nH]c4c([C@@H](C(=O)OC)C(=O)c4c3C)c3nc(cc4[nH]c(cc1n2)c(C=C)c4C)[C@@H](C)[C@@H]3CCC(O)=O CHEBI:38258
CC[C@@H]1[C@@H](C)c2cc3[nH]c(cc4nc([C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@@H]4C)c4[C@@H](C(=O)OC)C(=O)c5c(C)c(cc1n2)[nH]c45)c(C)c3C(C)=O CHEBI:41213
CCC1=C(C)\C2=C\C3=C(CC)C(C)=C(\C=C4/N=C(/C=C5\N\C(=C/C1=N2)C(C)=C5CCC(O)=O)C(CCC(O)=O)=C4C)N3C CHEBI:44085
Cc1cc(C)c(c(C)c1)-c1c2ccc(cc2)c(-c2c(C)cc(C)cc2C)c2ccc([nH]2)c(-c2ccccc2)c2ccc(n2)c(-c2c(C)cc(C)cc2C)c2ccc(cc2)c(-c2c(C)cc(C)cc2C)c2ccc([nH]2)c(-c2ccccc2)c2ccc1n2 CHEBI:47035
CCc1c(C)c2cc3[nH]c(cc4nc([C@@H](CCC(O)=O)[C@@H]4C)c4CC(=O)c5c(C)c(cc1n2)[nH]c45)c(C)c3C=C CHEBI:48398
CCc1c(C)c2cc3[nH]c(cc4nc([C@@H](CCC(O)=O)[C@@H]4C)c4[C@@H](C(O)=O)C(=O)c5c(C)c(cc1n2)[nH]c45)c(C)c3C=C CHEBI:48399
CCc1c(CC)c2cc3nc(cc4[nH]c(c(CC)c4CC)c4[nH]c(cc5nc(cc1[nH]2)c(CCCO)c5C)c(CC)c4CC)c(C)c3CCCO CHEBI:50285
CCc1c(CC)c2cc3nc(cc4[nH]c(c(CC)c4CC)c4[nH]c(cc5nc(cc1[nH]2)c(CCCOC(=O)N(CCOCCOCCOC)CCOCCOCCOC)c5C)c(CC)c4CC)c(C)c3CCCOC(=O)N(CCOCCOCCOC)CCOCCOCCOC CHEBI:50288
CCc1c(C)c2[nH]c1cc1nc(cc3[nH]c(cc4nc(cc5[nH]c2c(C)c5CC)c(C)c4CCCOC(=O)N(CCOCCOCCOC)CCOCCOCCOC)c(CC)c3CC)c(CCCOC(=O)N(CCOCCOCCOC)CCOCCOCCOC)c1C CHEBI:50289
CCc1c(CC)c2cc3nc(cc4[nH]c(c(C)c4C)c4[nH]c(cc5nc(cc1[nH]2)c(CCCOC(=O)N(CCOCCOCCOC)CCOCCOCCOC)c5C)c(C)c4C)c(C)c3CCCOC(=O)N(CCOCCOCCOC)CCOCCOCCOC CHEBI:50290
CCc1c(CC)c2cc3nc(cc4ccc([nH]4)c4ccc(cc5nc(cc1[nH]2)c(CCCOC(=O)N(CCOCCOCCOC)CCOCCOCCOC)c5C)[nH]4)c(C)c3CCCOC(=O)N(CCOCCOCCOC)CCOCCOCCOC CHEBI:50291
C1=C2C(=C(C=3N2[Mg]N4C(C=C5N=C(C3)C(=C5CC)CC)=C(C(=C4C=C6N=C1C(=C6CC)CC)CC)CC)CC)CC CHEBI:51227
C1=2N3C(C(=C4N=C(C(=C5N(C(=C(C6=NC(=C1C7=CC=CC=C7)C=C6)C8=CC=CC=C8)C=C5)[Mg]3)C=9C=CC=CC9)C=C4)C=%10C=CC=CC%10)=CC2 CHEBI:51228
c1ccc2c3nc(nc4[nH]c(nc5[nH]c(n3)c3ccccc53)c3ccccc43)c2c1 CHEBI:51587
c1ccc2c3nc(nc4[n-]c(nc5[n-]c(n3)c3ccccc53)c3ccccc43)c2c1 CHEBI:51591
c1ccc2c3nc(nc4nc(nc5[nH]c(nc6nc(nc7[nH]c(n3)c3ccccc73)c3ccccc63)c3ccccc53)c3ccccc43)c2c1 CHEBI:51597
CCc1c(CC)c2cc3[nH]c(cc4nc(cc5[nH]c(cc1n2)c(CC)c5CC)c(CC)c4CC)c(CC)c3CC CHEBI:52183
Brc1cc2cc3ccc(cc4ccc(cc5ccc(cc1[nH]2)n5)[nH]4)n3 CHEBI:52184
Brc1c2ccc(cc3ccc(cc4ccc(cc5ccc1[nH]5)n4)[nH]3)n2 CHEBI:52189
Bc1c2ccc(n2)c(B)c2ccc(cc3ccc(cc4ccc1[nH]4)n3)[nH]2 CHEBI:52194
Bc1c2ccc(cc3ccc(cc4ccc(cc5ccc1[nH]5)n4)[nH]3)n2 CHEBI:52197
Bc1cc2cc3ccc(cc4ccc(cc5ccc(cc1[nH]2)n5)[nH]4)n3 CHEBI:52204
Bc1c2ccc(n2)c(B)c2ccc([nH]2)c(B)c2ccc(n2)c(B)c2ccc1[nH]2 CHEBI:52207
Nc1ccccc1-c1c2ccc(n2)c(-c2ccccc2N)c2ccc([nH]2)c(-c2ccccc2N)c2ccc(n2)c(-c2ccccc2N)c2ccc1[nH]2 CHEBI:52277
Cc1cc(C)c(c(C)c1)-c1c2ccc(n2)c(-c2c(C)cc(C)cc2C)c2ccc([nH]2)c(-c2c(C)cc(C)cc2C)c2ccc(n2)c(-c2c(C)cc(C)cc2C)c2ccc1[nH]2 CHEBI:52278
c1ccc(cc1)-c1c2ccc(n2)c(-c2ccccc2)c2ccc([nH]2)c(-c2ccccc2)c2ccc(n2)c(-c2ccccc2)c2ccc1[nH]2 CHEBI:52279
Clc1c2ccc(cc3ccc(cc4ccc(cc5ccc1[nH]5)n4)[nH]3)n2 CHEBI:52542
c1cc2cc3cc(-c4cc5cc6ccc(cc7ccc(cc8ccc(cc4[nH]5)n8)[nH]7)n6)c(cc4ccc(cc5ccc(cc1n2)[nH]5)n4)[nH]3 CHEBI:52543
c1cc2cc3ccc([nH]3)c(-c3cc4cc5ccc(cc6ccc(cc7ccc(cc3[nH]4)n7)[nH]6)n5)c3ccc(cc4ccc(cc1n2)[nH]4)n3 CHEBI:52544
c1cc2cc3ccc([nH]3)c(-c3c4ccc(cc5ccc(cc6ccc(cc7ccc3[nH]7)n6)[nH]5)n4)c3ccc(cc4ccc(cc1n2)[nH]4)n3 CHEBI:52545
Oc1c2ccc(n2)c(O)c2ccc([nH]2)c(O)c2ccc(cc3ccc1[nH]3)n2 CHEBI:52546
Oc1c2ccc(cc3ccc([nH]3)c(O)c3ccc(cc4ccc1[nH]4)n3)n2 CHEBI:52547
O=Cc1c2ccc(cc3ccc(cc4ccc(cc5ccc1[nH]5)n4)[nH]3)n2 CHEBI:52548
O=Cc1cc2cc3ccc(cc4ccc(cc5ccc(cc1[nH]2)n5)[nH]4)n3 CHEBI:52558
c1cc2cc3ccc([nH]3)c(-c3c4ccc(cc5ccc([nH]5)c(-c5c6ccc(cc7ccc(cc8ccc(cc9ccc5[nH]9)n8)[nH]7)n6)c5ccc(cc6ccc3[nH]6)n5)n4)c3ccc(cc4ccc(cc1n2)[nH]4)n3 CHEBI:52563
Cc1c(CCC([O-])=O)c2cc3[nH]c(cc4nc(cc5[nH]c(cc1n2)c(C)c5C=C)c(C)c4C=C)c(C)c3CCC([O-])=O CHEBI:57306
CCc1c(C)c2cc3[nH]c(cc4nc([C@@H](CCC([O-])=O)[C@@H]4C)c4CC(=O)c5c(C)c(cc1n2)[nH]c45)c(C)c3C=C CHEBI:58742
CCc1c(C)c2cc3[nH]c(cc4nc([C@@H](CCC([O-])=O)[C@@H]4C)c4[C@@H](C([O-])=O)C(=O)c5c(C)c(cc1n2)[nH]c45)c(C)c3C=C CHEBI:58743
C=1C(=CC(=C(C1)N)C)C(=C2C=C(C(=[NH2+])C=C2)C)C=3C=C(C(=CC3)N)C CHEBI:87674
C1=2NC(C=C3N=C(C=C4NC(=CC5=NC(=C1)C(=C5CCC(=O)[O-])C)C(=C4C)CCC(=O)[O-])C(=C3C)CCC(=O)[O-])=C(C2C)CCC(=O)[O-] CHEBI:131725
C1=C2C(=C(C(N2)=CC3=NC(C(=C3C)CC)=CC=4NC(=C(C4C)CCC(=O)O)C=C5N=C1C(=C5CCC(=O)O)C)CC)C CHEBI:133626

Jul 07 '21 13:07 adalke