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customization added to tautomers.
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new base rules added.
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@stsouko
stsouko committed Dec 18, 2020
1 parent 11aa107 commit cfb18b3
Showing 1 changed file with 77 additions and 59 deletions.
136 changes: 77 additions & 59 deletions CGRtools/algorithms/tautomers.py
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Original file line number Diff line number Diff line change
Expand Up @@ -33,18 +33,18 @@
class Tautomers:
__slots__ = ()

def tautomerize(self: 'MoleculeContainer', *, prepare_molecules=True) -> bool:
def tautomerize(self: 'MoleculeContainer', *, prepare_molecules=True,
zwitter=True, ring_chain=True, keto_enol=True) -> bool:
"""
Convert structure to canonical tautomeric form. Return True if structure changed.
:param prepare_molecules: Standardize structures before. Aromatization and implicit hydrogens required.
"""
def key(m):
r = sum(len(r) for r in m.sssr) # more bigger rings is good
a = len(m.aromatic_rings) # more aromatics is good
return m.huckel_pi_electrons_energy - r - a

canon = min(self.enumerate_tautomers(prepare_molecules=prepare_molecules, full=False), key=key)
canon = min(self.enumerate_tautomers(prepare_molecules=prepare_molecules, full=False,
zwitter=zwitter, ring_chain=ring_chain, keto_enol=keto_enol), key=key)
if canon != self: # attach state of canonic tautomer to self
# atoms, radicals state, parsed_mapping and plane are unchanged
self._bonds = canon._bonds
Expand All @@ -59,18 +59,17 @@ def key(m):
return True
return False

def enumerate_tautomers(self: 'MoleculeContainer', *, prepare_molecules=True, full=True) -> \
def enumerate_tautomers(self: 'MoleculeContainer', *, prepare_molecules=True, full=True,
zwitter=True, ring_chain=True, keto_enol=True) -> \
Iterator['MoleculeContainer']:
"""
Enumerate all possible tautomeric forms of molecule. Supported hydrogen migration through delocalized chain.
O=C-C[H] <-> [H]O-C=C
O=C-C=C-C[H] <-> [H]O-C=C-C=C
O=C-C[H]-C=C <-> [H]O-C=C-C=C
O=C-C[H]-C=C <X> O=C-C=C-C[H] not directly possible
Enumerate all possible tautomeric forms of molecule.
:param prepare_molecules: Standardize structures before. Aromatization and implicit hydrogens required.
:param full: Do full enumeration.
:param zwitter: Enable acid-base tautomerization
:param ring_chain: Enable ring-chain tautomerization
:param keto_enol: Enable keto-enol tautomerization
"""
yield self.copy()
atoms_stereo = self._atoms_stereo
Expand All @@ -91,56 +90,59 @@ def enumerate_tautomers(self: 'MoleculeContainer', *, prepare_molecules=True, fu
while queue:
current = queue.popleft()

for mol in current._enumerate_zwitter_tautomers(full):
if mol not in seen:
seen[mol] = current
queue.append(mol)
if has_stereo:
mol = mol.copy()
mol._atoms_stereo.update(atoms_stereo)
mol._allenes_stereo.update(allenes_stereo)
mol._cis_trans_stereo.update(cis_trans_stereo)
mol._fix_stereo()
yield mol

for mol in current._enumerate_ring_chain_tautomers(full):
if mol not in seen:
seen[mol] = current
queue.append(mol)
if has_stereo:
mol = mol.copy()
mb = mol._bonds
mol._atoms_stereo.update((n, s) for n, s in atoms_stereo.items() if mb[n] == bonds[n])
mol._allenes_stereo.update(allenes_stereo)
mol._cis_trans_stereo.update(cis_trans_stereo)
mol._fix_stereo()
if zwitter:
for mol in current._enumerate_zwitter_tautomers(full):
if mol not in seen:
seen[mol] = current
queue.append(mol)
if has_stereo:
mol = mol.copy()
mol._atoms_stereo.update(atoms_stereo)
mol._allenes_stereo.update(allenes_stereo)
mol._cis_trans_stereo.update(cis_trans_stereo)
mol._fix_stereo()
yield mol

for mol, ket in current._enumerate_keto_enol_tautomers(full):
if mol not in seen:
seen[mol] = current
# prevent carbonyl migration
if current is not copy and not ket: # enol to ket potentially migrate ketone.
# search alpha hydroxy ketone inversion
before = seen[current]._sugar_groups
if any((k, e) in before for e, k in mol._sugar_groups):
continue

if has_stereo:
ster = mol.copy()
ster._atoms_stereo.update(atoms_stereo)
ster._allenes_stereo.update(allenes_stereo)
ster._cis_trans_stereo.update(cis_trans_stereo)
ster._fix_stereo()
yield ster
else:
if ring_chain:
for mol in current._enumerate_ring_chain_tautomers(full):
if mol not in seen:
seen[mol] = current
queue.append(mol)
if has_stereo:
mol = mol.copy()
mb = mol._bonds
mol._atoms_stereo.update((n, s) for n, s in atoms_stereo.items() if mb[n] == bonds[n])
mol._allenes_stereo.update(allenes_stereo)
mol._cis_trans_stereo.update(cis_trans_stereo)
mol._fix_stereo()
yield mol
if len(mol.aromatic_rings) > len(current.aromatic_rings):
# found new aromatic ring. flush queue and start from it.
queue.clear()

if keto_enol:
for mol, ket in current._enumerate_keto_enol_tautomers(full):
if mol not in seen:
seen[mol] = current
# prevent carbonyl migration
if current is not copy and not ket: # enol to ket potentially migrate ketone.
# search alpha hydroxy ketone inversion
before = seen[current]._sugar_groups
if any((k, e) in before for e, k in mol._sugar_groups):
continue

if has_stereo:
ster = mol.copy()
ster._atoms_stereo.update(atoms_stereo)
ster._allenes_stereo.update(allenes_stereo)
ster._cis_trans_stereo.update(cis_trans_stereo)
ster._fix_stereo()
yield ster
else:
yield mol
if len(mol.aromatic_rings) > len(current.aromatic_rings):
# found new aromatic ring. flush queue and start from it.
queue.clear()
queue.append(mol)
break
queue.append(mol)
break
queue.append(mol)

def _enumerate_zwitter_tautomers(self: Union['MoleculeContainer', 'Tautomers'], full=True):
atoms = self._atoms
Expand Down Expand Up @@ -610,6 +612,22 @@ def __stripped_base_rules(self):
q.add_bond(1, 2, 1)
rules.append(q)

# [O-]-[N+](=O)[O-]
q = query.QueryContainer()
q.add_atom('O', charge=-1)
q.add_atom('N', charge=1)
q.add_atom('O', charge=-1)
q.add_atom('O')
q.add_bond(1, 2, 1)
q.add_bond(2, 3, 1)
q.add_bond(2, 4, 2)
rules.append(q)

# ions
q = query.QueryContainer()
q.add_atom(ListElement(['O', 'F', 'Cl', 'Br', 'I']), charge=-1, neighbors=1)
rules.append(q)

return rules

@class_cached_property
Expand All @@ -623,7 +641,7 @@ def __base_rules(self):
q.add_bond(1, 2, 2)
rules.append(q)

# H2NC
# [N;H2][C;X4,a]
q = query.QueryContainer()
q.add_atom('N', neighbors=1)
q.add_atom('C', hybridization=1, heteroatoms=1)
Expand All @@ -639,7 +657,7 @@ def __base_rules(self):
q.add_bond(1, 3, 1)
rules.append(q)

# HN(C)C
# CN(C)C
q = query.QueryContainer()
q.add_atom('N')
q.add_atom('C', hybridization=1, heteroatoms=1)
Expand Down

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