I would have liked to include James Davidson; since I think sanifix3.py is
his code... but the emails on pages
http://www.mail-archive.com/rdkit-discuss@lists.sourceforge.net/msg01186.html
and
http://www.mail-archive.com/rdkit-discuss@lists.sourceforge.net/msg01162.html
are
quite sensibly spam protected. Anyway...
I have been using sanifix3.py to get around the "Can't kekulize mol"
errors... I have a number of molecules which still give me this error
(~1000 mols) even after running the sanifix script. I am attaching a
sanifix3.py script which fails with two of these molecules as an example. I
can supply more if needed.
Can someone guide me on how I can fix this to get it to work? (or are all
these molecules chemically nonsense)
Jean-Paul Ebejer
Early Stage Researcher
On 4 July 2011 20:44, Greg Landrum <greg.land...@gmail.com> wrote:
> On Mon, Jul 4, 2011 at 5:49 PM, JP <jeanpaul.ebe...@inhibox.com> wrote:
> >
> > Is there any obvious reason why the following 8 molecules in the attached
> > sdf file give a bunch of "kekulization" errors ?
> > Is it something to do with these lines -
> > M CHG 2 4 1 13 -1
> > M STY 1 1 DAT
> > M SAL 1 1 7
> > M SDT 1 MRV_IMPLICIT_H
> > M SDD 1 0.0000 0.0000 DR ALL 0 0
> > M SED 1 IMPL_H1
> > (using the now old 2010_12_1)
>
> Nope. Those molecules all contain bonds with bond-order set to
> aromatic and nitrogen-containing aromatic heterocycles where one
> (normally arbitrary) N needs an explicit H to make the ring aromatic.
> There are two problems here:
> 1) aromatic bond orders really shouldn't be used in SD files that
> aren't for query molecules.
> 2) The RDKit cannot figure out which N should have the H attached and,
> as is typical of the RDKit, doesn't try to guess. A method for
> randomly picking a tautomer that can be kekulized is described in
> these threads:
>
> http://www.mail-archive.com/rdkit-discuss@lists.sourceforge.net/msg01162.html
>
> http://www.mail-archive.com/rdkit-discuss@lists.sourceforge.net/msg01185.html
>
> Either fixing the SDF or running the "random" tautomer generator shoudl
> work.
>
> -greg
>
"""
This code belongs to James Davidson and is discussed here:
http://www.mail-archive.com/rdkit-discuss@lists.sourceforge.net/msg01185.html
http://www.mail-archive.com/rdkit-discuss@lists.sourceforge.net/msg01162.html
"""
mb = [ """MolPort-000-036-699
Marvin 05240819062D
39 44 0 0 0 0 999 V2000
-0.9093 -1.0027 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.1895 0.3923 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.4328 -1.6783 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-0.6446 -0.2242 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.9279 1.1739 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.6970 -1.2486 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-0.9248 -2.3416 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-1.7064 -2.0738 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-1.9991 0.2335 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.4698 1.7936 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
0.1619 -0.0623 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
1.7811 0.2584 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-2.5409 0.8532 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
2.5876 0.4204 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.2762 1.6316 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.3768 -1.8309 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.1183 1.3358 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
3.1356 -0.1962 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.7100 -0.6819 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.4266 0.7193 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1.5165 -0.5231 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1.2362 0.8781 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
2.8523 1.2051 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.3505 0.6881 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.8243 2.2513 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
3.9452 -0.0342 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
3.6619 1.3639 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.8954 1.3078 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.6338 2.0925 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
4.2068 0.7473 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
2.8678 -0.9777 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.9155 -1.2082 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.6508 -2.6094 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-4.7019 1.1459 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
3.9266 2.1454 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-4.9635 0.3643 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1.7250 -1.3577 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1.4604 -2.7619 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1.9991 -2.1361 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
2 4 1 0 0 0 0
3 1 4 0 0 0 0
4 1 1 0 0 0 0
5 2 4 0 0 0 0
6 1 4 0 0 0 0
7 3 4 0 0 0 0
8 6 4 0 0 0 0
9 2 4 0 0 0 0
10 5 4 0 0 0 0
11 4 1 0 0 0 0
12 22 1 0 0 0 0
13 9 4 0 0 0 0
14 12 1 0 0 0 0
15 10 4 0 0 0 0
16 3 1 0 0 0 0
17 5 2 0 0 0 0
18 14 4 0 0 0 0
19 11 1 0 0 0 0
20 11 1 0 0 0 0
21 19 1 0 0 0 0
22 20 1 0 0 0 0
23 14 4 0 0 0 0
24 13 4 0 0 0 0
25 15 4 0 0 0 0
26 18 4 0 0 0 0
27 23 4 0 0 0 0
28 24 4 0 0 0 0
29 25 4 0 0 0 0
30 27 4 0 0 0 0
31 18 1 0 0 0 0
32 16 1 0 0 0 0
33 16 1 0 0 0 0
34 28 1 0 0 0 0
35 27 1 0 0 0 0
36 34 1 0 0 0 0
37 32 1 0 0 0 0
38 33 1 0 0 0 0
39 37 1 0 0 0 0
8 7 4 0 0 0 0
12 21 1 0 0 0 0
39 38 1 0 0 0 0
15 13 4 0 0 0 0
29 28 4 0 0 0 0
30 26 4 0 0 0 0
M STY 1 1 DAT
M SAL 1 1 10
M SDT 1 MRV_IMPLICIT_H
M SDD 1 0.0000 0.0000 DR ALL 0 0
M SED 1 IMPL_H1
M END""",
"""MolPort-000-005-089
Marvin 05210810082D
19 21 0 0 0 0 999 V2000
1.4290 3.4338 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1.4290 2.6088 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
2.1434 2.1963 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
2.8579 2.6088 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
2.8579 3.4338 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
2.1434 3.8463 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
3.6425 2.3538 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
4.1274 3.0213 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
3.6425 3.6888 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
4.9525 3.0213 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
3.8974 1.5693 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
3.3454 0.9562 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
3.6004 0.1715 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
4.4073 0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
4.9594 0.6131 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
4.7044 1.3977 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.7145 3.8463 0.0000 N 0 3 0 0 0 0 0 0 0 0 0 0
0.7145 4.6714 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
0.0000 3.4338 0.0000 O 0 5 0 0 0 0 0 0 0 0 0 0
1 2 4 0 0 0 0
2 3 4 0 0 0 0
3 4 4 0 0 0 0
4 5 4 0 0 0 0
5 6 4 0 0 0 0
6 1 4 0 0 0 0
4 7 4 0 0 0 0
7 8 4 0 0 0 0
8 9 4 0 0 0 0
9 5 4 0 0 0 0
8 10 2 0 0 0 0
1 17 1 0 0 0 0
7 11 1 0 0 0 0
11 12 1 0 0 0 0
12 13 1 0 0 0 0
13 14 1 0 0 0 0
14 15 1 0 0 0 0
15 16 1 0 0 0 0
16 11 1 0 0 0 0
17 18 2 0 0 0 0
17 19 1 0 0 0 0
M CHG 2 17 1 19 -1
M STY 1 1 DAT
M SAL 1 1 9
M SDT 1 MRV_IMPLICIT_H
M SDD 1 0.0000 0.0000 DR ALL 0 0
M SED 1 IMPL_H1
M END
> <PUBCHEM_EXT_DATASOURCE_REGID>
MolPort-000-005-089
> <PUBCHEM_EXT_SUBSTANCE_URL>
http://www.molport.com/buy-chemicals/molecule-link/MolPort-000-005-089
> <PUBCHEM_EXT_DATASOURCE_URL>
http://www.molport.com
$$$$""" ]
from rdkit import Chem
from rdkit.Chem import AllChem
def FragIndicesToMol(oMol,indices):
em = Chem.EditableMol(Chem.Mol())
newIndices={}
for i,idx in enumerate(indices):
em.AddAtom(oMol.GetAtomWithIdx(idx))
newIndices[idx]=i
for i,idx in enumerate(indices):
at = oMol.GetAtomWithIdx(idx)
for bond in at.GetBonds():
if bond.GetBeginAtomIdx()==idx:
oidx = bond.GetEndAtomIdx()
else:
oidx = bond.GetBeginAtomIdx()
# make sure every bond only gets added once:
if oidx<idx:
continue
em.AddBond(newIndices[idx],newIndices[oidx],bond.GetBondType())
res = em.GetMol()
res.ClearComputedProps()
Chem.GetSymmSSSR(res)
res.UpdatePropertyCache(False)
res._idxMap=newIndices
return res
def _recursivelyModifyNs(mol,matches,indices=None):
if indices is None:
indices=[]
res=None
while len(matches) and res is None:
tIndices=indices[:]
nextIdx = matches.pop(0)
tIndices.append(nextIdx)
nm = Chem.Mol(mol.ToBinary())
nm.GetAtomWithIdx(nextIdx).SetNoImplicit(True)
nm.GetAtomWithIdx(nextIdx).SetNumExplicitHs(1)
cp = Chem.Mol(nm.ToBinary())
try:
Chem.SanitizeMol(cp)
except ValueError:
res,indices = _recursivelyModifyNs(nm,matches,indices=tIndices)
else:
indices=tIndices
res=cp
return res,indices
def AdjustAromaticNs(m,nitrogenPattern='[n&D2;r5,r6]'):
"""
default nitrogen pattern matches Ns in 5 rings and 6 rings in order to be able
to fix: O=c1ccncc1
"""
Chem.GetSymmSSSR(m)
m.UpdatePropertyCache(False)
# break non-ring bonds linking rings:
em = Chem.EditableMol(m)
linkers = m.GetSubstructMatches(Chem.MolFromSmarts('[r]!@[r]'))
for a,b in linkers:
em.RemoveBond(a,b)
nm = em.GetMol()
# build molecules from the fragments:
fragLists = Chem.GetMolFrags(nm)
frags = [FragIndicesToMol(nm,x) for x in fragLists]
# loop through the fragments in turn and try to aromatize them:
ok=True
for i,frag in enumerate(frags):
cp = Chem.Mol(frag.ToBinary())
try:
Chem.SanitizeMol(cp)
except ValueError:
matches = [x[0] for x in frag.GetSubstructMatches(Chem.MolFromSmarts(nitrogenPattern))]
lres,indices=_recursivelyModifyNs(frag,matches)
if not lres:
#print 'frag %d failed (%s)'%(i,str(fragLists[i]))
ok=False
break
else:
revMap={}
for k,v in frag._idxMap.iteritems():
revMap[v]=k
for idx in indices:
oatom = m.GetAtomWithIdx(revMap[idx])
oatom.SetNoImplicit(True)
oatom.SetNumExplicitHs(1)
if not ok:
return None
return m
if __name__=='__main__':
ms= (Chem.MolFromMolBlock(mb[0],False),
Chem.MolFromMolBlock(mb[1],False),
Chem.MolFromSmiles('c1cnc2cc3ccnc3cc12',False),
Chem.MolFromSmiles('c1cc2cc3ccnc3cc2n1',False),
Chem.MolFromSmiles('O=c1ccnc(c1)-c1cnc2cc3ccnc3cc12',False),
Chem.MolFromSmiles('O=c1ccnc(c1)-c1cc1',False),
)
for m in ms:
print '#---------------------'
try:
m.UpdatePropertyCache(False)
cp = Chem.Mol(m.ToBinary())
Chem.SanitizeMol(cp)
m = cp
print 'fine:',Chem.MolToSmiles(m)
except ValueError:
print 'adjust'
nm=AdjustAromaticNs(m)
if nm is not None:
Chem.SanitizeMol(nm)
print 'fixed:',Chem.MolToSmiles(nm)
else:
print 'still broken'------------------------------------------------------------------------------
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