File size: 4,929 Bytes
6e7d4ba
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
""" sanifix4.py

  Contribution from James Davidson
  adapted from: https://github.com/abradle/rdkitserver/blob/master/MYSITE/src/testproject/mol_parsing/sanifix.py
"""
from rdkit import Chem
from rdkit.Chem import AllChem
import warnings

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)
        nm.GetAtomWithIdx(nextIdx).SetNoImplicit(True)
        nm.GetAtomWithIdx(nextIdx).SetNumExplicitHs(1)
        cp = Chem.Mol(nm)
        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)
        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.items():
                    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



def fix_mol(m):
    if m is None:
        return None
    try:
        m.UpdatePropertyCache(False)
        cp = Chem.Mol(m.ToBinary())
        Chem.SanitizeMol(cp)
        m = cp
        # print('fine:',Chem.MolToSmiles(m))
        warnings.warn(f'fine: {Chem.MolToSmiles(m)}')
        return m
    except ValueError:
        # print('adjust')
        warnings.warn('adjust')
        nm=AdjustAromaticNs(m)
        if nm is not None:
            try:
                Chem.SanitizeMol(nm)
                # print('fixed:',Chem.MolToSmiles(nm))
                warnings.warn(f'fixed: {Chem.MolToSmiles(nm)}')
            except ValueError:
                # print('still broken')
                warnings.warn('still broken')
        else:
            # print('still broken')
            warnings.warn('still broken')
        return nm

if __name__=='__main__':
    ms = [x for x in open("18.sdf").read().split("$$$$\n")]
    for txt_m in ms:
        if not txt_m:
            continue
        m = Chem.MolFromMolBlock(txt_m, False)
        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')