Many Thanks for this Greg... as usual your helpful attitude adds so much more value to this already brilliant toolkit.
I have added another three testing cases which fail (attached)...I am not sure whether these are "new" cases, or instances of your supplied failing case (#9 in the attached: O=c1ccnc(c1)-c1cc1). I basically took three cases at random from my "failing" sdf. (I can keep you entertained for hours! :) ) Jean-Paul Ebejer Early Stage Researcher On 10 August 2011 04:45, Greg Landrum <greg.land...@gmail.com> wrote: > On Tue, Aug 9, 2011 at 1:53 PM, JP <jeanpaul.ebe...@inhibox.com> wrote: > > 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) > > Oh, that was a fun one. > The problem came because of the aromatic nitrogens attached to other > ring atoms. These were not being properly handled in the fragmentation > process. I've attached a corrected version, sanifix4.py > > -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 http://www.mail-archive.com/rdkit-discuss@lists.sourceforge.net/msg01900.html """ mb = [ """MolPort-000-002-029 Marvin 05210809592D 18 20 0 0 0 0 999 V2000 0.0000 2.1304 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 1.3054 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7144 0.8929 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4290 1.3054 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4290 2.1304 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7144 2.5429 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2136 1.0505 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.6985 1.7179 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2136 2.3854 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.5235 1.7179 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 4.2211 1.7179 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7060 1.0505 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 5.4906 1.3054 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4906 2.1304 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7060 2.3854 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 6.1580 0.8205 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9117 1.1561 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0718 0.0000 0.0000 O 0 0 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 1 0 0 0 0 10 11 1 0 0 0 0 11 12 4 0 0 0 0 12 13 4 0 0 0 0 13 14 4 0 0 0 0 14 15 4 0 0 0 0 15 11 4 0 0 0 0 13 16 1 0 0 0 0 16 17 2 0 0 0 0 16 18 1 0 0 0 0 M STY 2 1 DAT 2 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 M SAL 2 1 12 M SDT 2 MRV_IMPLICIT_H M SDD 2 0.0000 0.0000 DR ALL 0 0 M SED 2 IMPL_H1 M END > <PUBCHEM_EXT_DATASOURCE_REGID> MolPort-000-002-029 > <PUBCHEM_EXT_SUBSTANCE_URL> http://www.molport.com/buy-chemicals/molecule-link/MolPort-000-002-029 > <PUBCHEM_EXT_DATASOURCE_URL> http://www.molport.com $$$$ """, """MolPort-000-003-259 Marvin 05210810032D 20 21 0 0 0 0 999 V2000 2.8546 1.2418 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8546 0.4139 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5684 1.6558 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.1411 1.6558 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1411 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5684 0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 4.2821 1.2418 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4274 1.2418 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4274 0.4139 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2821 0.4139 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9958 1.6558 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7136 1.6558 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7136 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9958 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7095 1.2418 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 1.2418 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.4139 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4231 1.6558 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1340 1.2418 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4231 2.4751 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 2 4 0 0 0 0 1 3 4 0 0 0 0 1 4 4 0 0 0 0 2 5 4 0 0 0 0 2 6 4 0 0 0 0 3 7 4 0 0 0 0 4 8 4 0 0 0 0 5 9 4 0 0 0 0 6 10 4 0 0 0 0 7 11 1 0 0 0 0 8 12 1 0 0 0 0 9 13 1 0 0 0 0 10 14 2 0 0 0 0 11 15 1 0 0 0 0 12 16 1 0 0 0 0 13 17 1 0 0 0 0 15 18 1 0 0 0 0 18 19 1 0 0 0 0 18 20 2 0 0 0 0 7 10 4 0 0 0 0 8 9 4 0 0 0 0 M STY 1 1 DAT M SAL 1 1 6 M SDT 1 MRV_IMPLICIT_H M SDD 1 0.0000 0.0000 DR ALL 0 0 M SED 1 IMPL_H1 M END > <PUBCHEM_EXT_DATASOURCE_REGID> MolPort-000-003-259 > <PUBCHEM_EXT_SUBSTANCE_URL> http://www.molport.com/buy-chemicals/molecule-link/MolPort-000-003-259 > <PUBCHEM_EXT_DATASOURCE_URL> http://www.molport.com $$$$""", """MolPort-000-014-293 Marvin 05240818432D 35 39 0 0 0 0 999 V2000 -0.2869 0.0074 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.4929 0.1839 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5663 0.9930 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.1765 1.3460 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.7061 0.7502 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2878 2.1624 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.8244 1.4931 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2878 0.8164 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.0968 1.9123 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0968 1.0666 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3540 -0.3456 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.1621 -0.3825 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 2.5743 -0.6253 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9865 -0.8752 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7061 -0.6987 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5520 0.7502 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7662 -0.5958 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4346 -1.4417 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9785 1.4563 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9785 -0.0957 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9427 0.2574 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8029 2.3390 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8029 0.6399 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8100 -1.6844 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2869 -1.4417 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5225 -0.6987 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3620 -1.1254 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3028 0.8164 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5090 1.9492 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5090 1.0666 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4793 -2.2507 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9418 -1.4417 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2222 -1.9344 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6694 -2.1478 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5225 -2.1478 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2 1 4 0 0 0 0 3 2 4 0 0 0 0 4 5 4 0 0 0 0 5 1 4 0 0 0 0 6 7 4 0 0 0 0 7 19 1 0 0 0 0 8 7 4 0 0 0 0 9 6 4 0 0 0 0 10 8 4 0 0 0 0 11 13 1 0 0 0 0 12 2 1 0 0 0 0 13 20 1 0 0 0 0 14 11 1 0 0 0 0 15 1 1 0 0 0 0 16 5 1 0 0 0 0 17 14 4 0 0 0 0 18 13 2 0 0 0 0 19 16 1 0 0 0 0 20 12 1 0 0 0 0 21 17 1 0 0 0 0 22 9 4 0 0 0 0 23 10 4 0 0 0 0 24 14 4 0 0 0 0 25 15 4 0 0 0 0 26 15 4 0 0 0 0 27 17 4 0 0 0 0 28 21 1 0 0 0 0 29 22 4 0 0 0 0 30 23 4 0 0 0 0 31 24 4 0 0 0 0 32 26 4 0 0 0 0 33 31 4 0 0 0 0 34 25 4 0 0 0 0 35 32 4 0 0 0 0 3 4 4 0 0 0 0 35 34 4 0 0 0 0 9 10 4 0 0 0 0 29 30 4 0 0 0 0 33 27 4 0 0 0 0 M STY 1 1 DAT M SAL 1 1 8 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-000-014-293 > <PUBCHEM_EXT_SUBSTANCE_URL> http://www.molport.com/buy-chemicals/molecule-link/MolPort-000-014-293 > <PUBCHEM_EXT_DATASOURCE_URL> http://www.molport.com > <STOCK> 8 > <STOCKMEASURE> 234 $$$$""" ] 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&H0;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]')) plsFix=set() for a,b in linkers: em.RemoveBond(a,b) plsFix.add(a) plsFix.add(b) nm = em.GetMol() for at in plsFix: at=nm.GetAtomWithIdx(at) if at.GetIsAromatic() and at.GetAtomicNum()==7: at.SetNumExplicitHs(1) at.SetNoImplicit(True) # 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.MolFromMolBlock(mb[2],False), Chem.MolFromSmiles('O=c1ccc2ccccc2n1', False), Chem.MolFromSmiles('Cc1nnnn1C', False), Chem.MolFromSmiles('CCc1ccc2nc(=O)c(cc2c1)Cc1nnnn1C1CCCCC1', False), Chem.MolFromSmiles('c1cnc2cc3ccnc3cc12', False), Chem.MolFromSmiles('c1cc2cc3ccnc3cc2n1', False), Chem.MolFromSmiles('O=c1ccnc(c1)-c1cnc2cc3ccnc3cc12', False), Chem.MolFromSmiles('O=c1ccnc(c1)-c1cc1', False), ) fine = fixed = broken = 0 for i,m in enumerate(ms): print '#---------------------' try: m.UpdatePropertyCache(False) cp = Chem.Mol(m.ToBinary()) Chem.SanitizeMol(cp) m = cp print 'fine:',Chem.MolToSmiles(m) fine += 1 except ValueError: nm=AdjustAromaticNs(m) if nm is not None: Chem.SanitizeMol(nm) print 'fixed:',Chem.MolToSmiles(nm) fixed += 1 else: print 'still broken:', i broken += 1 print "%d fine, %d fixed, %d still broken (%d total)" % (fine, fixed, broken, (fine+fixed+broken))
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