def RemoveBond(mol, bond):
if bond.HasProp('group'):
raise MutateFail(mol,
'Protected bond (in group) passed to RemoveBond.')
if not bond.IsInRing():
raise MutateFail(mol, 'Non-ring bond passed to RemoveBond')
mol.RemoveBond(bond.GetBeginAtomIdx(), bond.GetEndAtomIdx())
return mol
def MakeMutations(candidate):
''' The mutations, based on not-aromatic SMILES'''
# 1. Kekulize:
try:
Chem.Kekulize(candidate, True)
except ValueError:
print "MakeMutation. Kekulize Error:", Chem.MolToSmiles(candidate)
raise MutateFail(candidate)
# 2. Mutate
candidate = SingleMutate(candidate)
# 3. SetAromaticity again
try:
if aromaticity: Chem.SetAromaticity(candidate)
candidate = Finalize(candidate, tautomerize=False)
except ValueError:
print "MakeMutation. SetAromaticity Error:", Chem.MolToSmiles(
candidate)
raise MutateFail(candidate)
return candidate
def AddAroRing(mol):
freesinglebonds = GetFreeBonds(mol, order=1, sides=True)
freedoublebonds = GetFreeBonds(mol, order=2, notprop='group')
triplebonds = filter(lambda bond: bond.GetBondType() == bondorder[3],
mol.GetBonds())
correctbonds = freedoublebonds + triplebonds + freesinglebonds
if len(correctbonds) < 1: raise MutateFail()
bond = random.choice(correctbonds)
# if double bond
if all(atom.GetImplicitValence()
for atom in (bond.GetBeginAtom(), bond.GetEndAtom())):
pass
elif bond.GetBondType() == bondorder[3]:
bond.SetBondType(bondorder[2])
else:
print "wrong kind of atom given"
raise MutateFail()
def AwithLabel(label, idx=True):
atom = filter(lambda atom: atom.HasProp(label), mol.GetAtoms())[0]
if idx:
return atom.GetIdx()
else:
return atom
butadiene = Chem.MolFromSmiles('C=CC=C')
butadiene.GetAtomWithIdx(0).SetBoolProp('buta1', True)
butadiene.GetAtomWithIdx(3).SetBoolProp('buta2', True)
bond.GetBeginAtom().SetBoolProp('ah1', True)
bond.GetEndAtom().SetBoolProp('ah2', True)
mol = Chem.RWMol(Chem.CombineMols(mol, butadiene))
try:
mol.AddBond(AwithLabel('buta1'), AwithLabel('ah1'), bondorder[1])
mol.AddBond(AwithLabel('buta2'), AwithLabel('ah2'), bondorder[1])
except RuntimeError:
raise MutateFail()
finally:
for prop in ['buta1', 'buta2', 'ah1', 'ah2']:
AwithLabel(prop, idx=False).ClearProp(prop)
return mol
def AddBond(mol):
# NB! This function was overloaded and atoms where possible arguments
# Not anymore possible to get a cleaner interface
natoms = mol.GetNumAtoms()
if natoms < 5: raise MutateFail() #don't create 4-member rings
#Don't create non-planar graphs (note that this does not prevent
#all non-planar graphs, but it does prevent some)
if natoms >= 3 and mol.GetNumBonds() >= 3 * natoms - 6:
raise MutateFail()
# List of atoms that can form new bonds
atoms = [
atom for atom in GetAtoms(mol, notprop='protected')
if EmptyValence(atom) > 0
]
if len(atoms) < 2: raise MutateFail()
for i in range(MAXTRY):
atom1 = random.choice(atoms)
atom2 = random.choice(atoms)
if atom1 == atom2: continue
# new rather strict criteria;
if atom1.IsInRing() and atom2.IsInRing():
#print "continue because both atoms in ring"
continue
# Only make rings of size 5-7
if not (5 <= len(
Chem.GetShortestPath(mol, atom1.GetIdx(), atom2.GetIdx())) <=
7):
continue
nfreebonds1 = EmptyValence(atom1)
nfreebonds2 = EmptyValence(atom2)
if nfreebonds2 < nfreebonds1: nfreebonds1 = nfreebonds2
assert nfreebonds1 > 0
order = random.randrange(1, nfreebonds1 + 1)
mol.AddBond(atom1.GetIdx(), atom2.GetIdx(), bondorder[order])
return mol
# if here, mutation failed
raise MutateFail()
def GetFragment(mol):
#print "in get fragment with:", Chem.MolToSmiles(mol)
tried = []
for itry in xrange(MAXTRY):
frag = Chem.RWMol(mol)
#frag.ClearComputedProps()
ResetProps(frag)
#Cut an acyclic bond to break molecule in 2
# get the ring bond ids. this gives a tuple of tuple for every ring
ringbondids = frag.GetRingInfo().BondRings()
# flatten this tuple to a 1D set
ringbondids = list(
set([bond for subset in ringbondids for bond in subset]))
# get all the bonds that are NOT ringbonds or already tried
bonds = [
bond for bond in mol.GetBonds()
if bond.GetIdx() not in tried + ringbondids
]
if len(bonds) == 0: break
if debug: print "CX0",
# choose a bond
delbond = random.choice(bonds)
tried.append(delbond.GetIdx())
# get atom indices of the bond
i, j = (delbond.GetBeginAtomIdx(), delbond.GetEndAtomIdx())
frag.RemoveBond(i, j)
# get new fragments as two new normal Mol objects
try:
frags = Chem.GetMolFrags(frag, asMols=True)
except ValueError:
print "frag:", Chem.MolToSmiles(frag)
print "mol:", Chem.MolToSmiles(mol)
break
molfrags = [Chem.MolToSmiles(x, True) for x in frags]
if len(frags) < 2:
#print "only one frag"
continue
#Check to make sure fragments have at least 2 atoms
if any(frag.GetNumAtoms() < 2 for frag in frags):
#print "not enough atoms on frag"
continue
#print molfrags
# convert to RWMols?
frags = map(Chem.RWMol, frags)
return frags
# If here, we failed to find a good bond to cut
#print "no nice bond to cut"
raise MutateFail()
def FlipBond(mol, bond):
if bond.HasProp('group'):
raise MutateFail(mol, 'In-group bond passed to FlipBond')
oldorder = int(bond.GetBondTypeAsDouble())
atom1 = bond.GetBeginAtom()
atom2 = bond.GetEndAtom()
full = False
if EmptyValence(atom1) == 0: full = True
if EmptyValence(atom2) == 0: full = True
if oldorder == 1 and full:
raise MutateFail()
elif oldorder == 1:
add = 1
elif oldorder == 3:
add = -1
elif oldorder == 2 and full:
add = -1
else:
add = random.choice((-1, 1))
bond.SetBondType(bondorder[oldorder + add])
return mol
def FlipBond(mol):
bonds = list(GetBonds(mol, notprop='group'))
if len(bonds) == 0: raise MutateFail()
bond = random.choice(bonds)
oldorder = int(bond.GetBondTypeAsDouble())
atom1 = bond.GetBeginAtom()
atom2 = bond.GetEndAtom()
full = False
if EmptyValence(atom1) == 0: full = True
if EmptyValence(atom2) == 0: full = True
if oldorder == 1 and full:
raise MutateFail()
elif oldorder == 1:
add = 1
elif oldorder == 3:
add = -1
elif oldorder == 2 and full:
add = -1
else:
add = random.choice((-1, 1))
bond.SetBondType(bondorder[oldorder + add])
return mol
def FlipAtom(mol):
atoms = filter(CanChangeAtom, mol.GetAtoms())
if len(atoms) == 0: raise MutateFail()
atom = random.choice(atoms)
changed = False
neighbors = list(atom.GetNeighbors())
valence = atom.GetExplicitValence() + atom.GetNumRadicalElectrons()
# Add a halogen, if possible
# we only add halogens when neighbor and neighbor-neighbor only C
if valence == 1:
if (len(halogens) > 0 and random.random() > 0.6
and neighbors[0].GetAtomicNum() == 6):
CanAddHalogen = True
nextneighbors = neighbors[0].GetNeighbors()
for nb in nextneighbors:
if (nb.GetAtomicNum() != 6 and nb.GetIdx() != atom.GetIdx()):
CanAddHalogen = False
break
if CanAddHalogen:
atom.SetAtomicNum(random.choice(halogens))
return mol
# # # # # # # # #
# Regular atom switching
atnum = atom.GetAtomicNum()
elems = [el for el in elements if el != atnum]
for itry in range(50):
cand = random.choice(elems)
if MaxValence[cand] >= valence:
atom.SetAtomicNum(cand)
return mol
if not changed:
raise MutateFail() # if here, mutation failed ...
return mol
def AddAtom(mol):
# 5. add an atom
atoms = GetAtoms(mol, notprop='protected')
bonds = GetBonds(mol, notprop='group')
if len(atoms) < 1: raise MutateFail()
obj = random.choice(atoms + bonds)
# If passed a bond, insert an atom into it
if type(obj) == Chem.Bond:
if obj.HasProp('group'):
raise MutateFail(mol, 'Grouped bond passed to AddAtom')
# note that we really nead the atoms here because the Idx may change
# after adding a new atom to the molecule
atom1 = obj.GetBeginAtom()
atom2 = obj.GetEndAtom()
mol.RemoveBond(atom1.GetIdx(), atom2.GetIdx())
newatomid = mol.AddAtom(Chem.Atom(6))
mol.AddBond(atom1.GetIdx(), newatomid, bondorder[1])
mol.AddBond(atom2.GetIdx(), newatomid, bondorder[1])
#Otherwise, make a new sidechain (or add a terminal atom)
elif type(obj) == Chem.Atom and EmptyValence(obj) > 0:
if obj.HasProp('protected'):
raise MutateFatal(mol, 'Trying to add atom to protected atom.')
# choose an atom to add
atnum = obj.GetAtomicNum()
elems = [el for el in elements if el != atnum]
if atnum == 6: # only add halogens to carbons
elems.extend(halogens)
cand = random.choice(elems)
# and add it
newatomid = mol.AddAtom(Chem.Atom(cand))
mol.AddBond(obj.GetIdx(), newatomid, bondorder[1])
else:
raise MutateFail()
return mol
def AddFusionRing(mol):
try:
p = Chem.MolFromSmarts('[h]@&=*(@*)@[h]')
matches = mol.GetSubstructMatches(p)
except RuntimeError:
raise MutateFail()
if len(matches) == 0:
raise MutateFail()
match = random.choice(matches)
if mol.GetAtomWithIdx(match[-1]).GetNumRadicalElectrons():
raise MutateFail()
def AwithLabel(label, idx=True):
atom = filter(lambda atom: atom.HasProp(label), mol.GetAtoms())[0]
if idx:
return atom.GetIdx()
else:
return atom
propene = Chem.MolFromSmiles('C=CC')
propene.GetAtomWithIdx(0).SetBoolProp('propane1', True)
propene.GetAtomWithIdx(2).SetBoolProp('propane2', True)
mol.GetAtomWithIdx(match[3]).SetBoolProp('ah1', True)
mol.GetAtomWithIdx(match[0]).SetBoolProp('ah2', True)
mol = Chem.RWMol(Chem.CombineMols(mol, propene))
try:
mol.AddBond(AwithLabel('propane1'), AwithLabel('ah1'), bondorder[1])
mol.AddBond(AwithLabel('propane2'), AwithLabel('ah2'), bondorder[1])
except RuntimeError:
raise MutateFail()
finally:
for prop in ['propane1', 'propane2', 'ah1', 'ah2']:
AwithLabel(prop, idx=False).ClearProp(prop)
return mol
def AddAtom(mol, obj):
# If passed a bond, insert an atom into it
if type(obj) == Chem.Bond:
if obj.HasProp('group'):
raise MutateFail(mol, 'Grouped bond passed to AddAtom')
# note that we really nead the atoms here because the Idx may change
# after adding a new atom to the molecule
atom1 = obj.GetBeginAtom()
atom2 = obj.GetEndAtom()
mol.RemoveBond(atom1.GetIdx(), atom2.GetIdx())
newatomid = mol.AddAtom(Chem.Atom(6))
mol.AddBond(atom1.GetIdx(), newatomid, bondorder[1])
mol.AddBond(atom2.GetIdx(), newatomid, bondorder[1])
#Otherwise, make a new sidechain (or add a terminal atom)
elif type(obj) == Chem.Atom and EmptyValence(obj) > 0:
if obj.HasProp('protected'):
raise MutateFatal(mol, 'Trying to add atom to protected atom.')
newatomid = mol.AddAtom(Chem.Atom(6))
mol.AddBond(obj.GetIdx(), newatomid, bondorder[1])
else:
raise MutateFail()
return mol
def __call__(self, mol):
Chem.Kekulize(mol, True)
try:
mol = self.mutator(mol)
except MutateFail as e:
raise
except RuntimeError as e:
print "RuntimeError in Mutator:", self.mutator, self.name
print "repr(e):", repr(e)
raise MutateFail()
except Exception as e:
if 'MutateFail' in repr(e):
raise MutateFail()
else:
raise
if mol is None:
raise MutateFail()
mol = Finalize(mol, tautomerize=False, aromatic=False)
if type(mol) == Chem.Mol:
mol = Chem.RWMol(mol)
return mol
def DelBond(mol):
bondringids = mol.GetRingInfo().BondRings()
# need to flatten bondringids:
if len(bondringids) > 0:
# fancy manner to flatten a list of tuples with possible duplicates
#bondringids = set.intersection(*map(set, bondringids))
bondringids = set.union(*map(set, bondringids))
bonds = GetIBonds(bondringids, mol, notprop='group')
else:
raise MutateFail()
try:
bond = random.choice(bonds)
except IndexError:
print bondringids
mol.RemoveBond(bond.GetBeginAtomIdx(), bond.GetEndAtomIdx())
#print "succesful delbond:", Chem.MolToSmiles(mol)
return mol
def Finalize(mol, tautomerize=None, aromatic=aromaticity):
''' This function makes sure that a new mutated/crossover/fixfilter molecule:
- corrects the implicit valence
- removes data from parent molecules.
- optionally converts the molecule to its canonical tautomer
- checks if it is a valid molecule, i.e. Sanitize step. (without aromaticity)
'''
# 1.
try:
mol.UpdatePropertyCache()
except ValueError:
raise MutateFail(mol)
# 2.
RW = type(mol) == Chem.RWMol
# 3.
ResetProps(mol)
# 4.
if canonicalTautomer and not tautomerize is False:
mol = Tautomerize(mol, aromatic)
# 5.
try:
Sanitize(mol, aromatic)
except Exception as e:
print "Error in Finalize with", Chem.MolToSmiles(mol, False),
if verbose: print e,
if debug:
for item in traceback.extract_stack():
print item
# 6.
if aromatic: Chem.SetAromaticity(mol)
# 7.
if RW and not type(mol) == Chem.RWMol:
return Chem.RWMol(mol)
else:
return mol
def Tautomerize(mol):
try:
if mol.GetBoolProp('tautomerized'): return
except KeyError:
pass
smi1 = Chem.MolToSmiles(mol)
from molvs import Standardizer
s = Standardizer()
try:
s.standardize(mol)
except ValueError as e:
MutateFail(mol)
return False
#from molvs.tautomer import TautomerCanonicalizer
#t = TautomerCanonicalizer()
#t.canonicalize(mol)
mol.SetBoolProp('tautomerized', True)
smi2 = Chem.MolToSmiles(mol)
if not smi1 == smi2: print "tautomerized:", smi1, 'to:', smi2
return True
def SingleMutate(candidateraw):
if candidateraw is None: raise ValueError('candidate is none')
else: candidate = Chem.RWMol(candidateraw)
global stats
parent = candidate.GetProp('isosmi')
ResetProps(candidate)
change = False
candidate.SetProp('parent', parent)
for mutationtype, mutator in mutators.items():
if random.random() < mutator.p:
#print "in mutate:", mutationtype, Chem.MolToSmiles(candidate),
change = True
stats[mutator.nname] += 1
try:
candidate = mutator(candidate)
# I don't understand why these errors are not similar?! but this works
except MutateFail as e:
stats[mutator.nnameFail] += 1
except Exception as e:
if 'MutateFail' in repr(e):
#print "exotic MutateFail"
stats[mutator.nnameFail] += 1
else:
print "Exception is not MutateFail!"
print e, repr(e), type(e)
raise
# should we allow multiple mutation at the same time:
# if not:
# break
if not change:
stats['nNoMutation'] += 1
raise MutateFail()
return candidate
def Tautomerize(mol, aromatic=aromaticity):
try:
if mol.GetBoolProp('tautomerized'): return mol
except KeyError:
pass
Chem.SanitizeMol(mol)
if not (aromatic or aromaticity):
Chem.Kekulize(mol, True)
smi1 = Chem.MolToSmiles(mol)
from molvs import Standardizer
s = Standardizer()
try:
molnew = s.standardize(mol)
except ValueError as e:
raise MutateFail(mol)
if not aromatic:
Chem.Kekulize(molnew, True)
smi2 = Chem.MolToSmiles(molnew)
if smi1 == smi2:
# we return mol because it contains some properties
# tautomerized mols need to get the props again
mol.SetBoolProp('tautomerized', True)
return mol
else:
if mol.HasProp('failedfilter'):
ff = mol.GetProp('failedfilter')
molnew.SetProp('failedfilter', ff)
#print "tautomerized:", smi1, 'to:', smi2
with open('tautomerized.smi', 'a') as f:
f.write("{} {}\n".format(smi1, smi2))
molnew.SetBoolProp('tautomerized', True)
return molnew
def SwitchAtom(mol, atom):
if atom.HasProp('group') and not atom.HasProp('grouprep'):
raise MutateFail(mol, 'protected or grouped atom passed to switchatom')
changed = False
neighbors=list(atom.GetNeighbors())
# # # # # # # # # # # # #
# from Filters import OptSulfone
# Special rules for sulfurs that can optionally be sulfones
#if atom.GetAtomicNum()==16 and len(OptSulfone)>0:
# SulfCand=set()
# for group in OptSulfone:
# for match in mol.GetSubstructMatches(group, True):
# for mat in GetIAtoms(match, mol):
# if mat.target.IsSulfur(): SulfCand.add(mat.target)
# if atom in SulfCand and random.random()>0.4:
# if atom.HasProp('grouprep'):
# RemoveGroup(mol,atom.GetProp('group'))
# return
# elif not atom.HasProp('group'):
# MakeSulfone(mol,atom)
# return
#If it's a group representative, switching it will delete the
#rest of the group; since they're hard to create, they're also
#hard to destroy
#if atom.HasProp('grouprep':
# if random.random()>0.3:
# RemoveGroup(mol,atom.GetProp('group'))
# changed=True
# else:
# raise MutateFail()
# # # # # # # # # # # # # #
#Special cases for Nitro groups and halogens,
#which can only be on aromatic rings
#if ( atom.GetExplicitValence()==1
# and neighbors[0].IsAromatic() ):
# Add a halogen, if possible
# we only add halogens when neighbor and neighbor-neighbor only C
if atom.GetExplicitValence()==1:
if (len(halogens)>0
and random.random()>0.6
and neighbors[0].GetAtomicNum()==6):
CanAddHalogen=True
nextneighbors=neighbors[0].GetNeighbors()
for nb in nextneighbors:
if ( nb.GetAtomicNum() != 6
and nb.GetIdx() != atom.GetIdx()):
CanAddHalogen=False
break
if CanAddHalogen:
atom.SetAtomicNum( random.choice(halogens))
return
# If not a halogen, maybe make a nitro group
# if random.random() < 0.15:
# MakeNitro(mol,atom)
# return
# # # # # # # # #
# Regular atom switching
atnum = atom.GetAtomicNum()
elems = [el for el in elements if el != atnum]
for itry in range(50):
cand = random.choice(elems)
if MaxValence[cand] >= atom.GetExplicitValence():
atom.SetAtomicNum(cand)
return
if not changed:
raise MutateFail() # if here, mutation failed ...
return mol
def RemoveAtom(mol, atom):
#
# Deal with special groups
#
if atom.HasProp('protected') or atom.HasProp('fixed'):
raise MutateFatal(mol,
'Protected or fixed atom passed to' + " RemoveAtom.")
Degree = atom.GetDegree()
if debug: print "D{:d}".format(Degree)
# If atom is the representative of a larger group (e.g. N in nitro group)
# delete the entire group
if atom.HasProp('grouprep'):
groupnum = atom.GetProp('group')
RemoveGroup(mol, groupnum)
#If there's only one atom, refuse to remove it
if len(atom.GetNeighbors()) == 0:
raise MutateFail(mol)
#Remove a terminal atom:
elif Degree == 1:
for bond in atom.GetBonds():
mol.RemoveBond(bond.GetBeginAtomIdx(), bond.GetEndAtomIdx())
mol.RemoveAtom(atom.GetIdx())
# until here it seems fine
#Remove an in-chain atom:
#
#NOT WORKING WELL
elif Degree == 2:
#print Chem.MolToSmiles(mol, True)
nbr = []
for neighb in atom.GetNeighbors():
nbr.append(neighb)
for bond in atom.GetBonds():
mol.RemoveBond(bond.GetBeginAtomIdx(), bond.GetEndAtomIdx())
mol.RemoveAtom(atom.GetIdx())
# this line give indexerrors:
mol.AddBond(nbr[0].GetIdx(), nbr[1].GetIdx(), bondorder[1])
elif True:
pass
#Remove a 3-bond atom:
elif Degree == 3:
nbr = []
nbrCarbon = []
nChoice = 3
for neighb in atom.GetNeighbors():
nbr.append(neighb)
if neighb.GetAtomicNum()==6 and \
len(neighb.GetNeighbors())==3:
nChoice = nChoice + 1
nbrCarbon.append(neighb)
choose = random.randrange(0, nChoice, 1)
for bond in atom.GetBonds():
mol.RemoveBond(bond.GetBeginAtomIdx(), bond.GetBeginAtomIdx())
mol.RemoveAtom(atom.GetIdx())
if choose == 0:
mol.AddBond(nbr[0].GetIdx(), nbr[1].GetIdx(), bondorder[1])
mol.AddBond(nbr[1].GetIdx(), nbr[2].GetIdx(), bondorder[1])
elif choose == 1:
mol.AddBond(nbr[0].GetIdx(), nbr[2].GetIdx(), bondorder[1])
mol.AddBond(nbr[2].GetIdx(), nbr[1].GetIdx(), bondorder[1])
elif choose == 2:
mol.AddBond(nbr[0].GetIdx(), nbr[1].GetIdx(), bondorder[1])
mol.AddBond(nbr[2].GetIdx(), nbr[0].GetIdx(), bondorder[1])
else:
for neighb in nbr:
if not neighb.GetIdx() == nbrCarbon[choose - 3].GetIdx():
mol.AddBond(neighb.GetIdx(),
nbrCarbon[choose - 3].GetIdx(), bondorder[1])
#Remove a 4-bond atom
elif Degree == 4:
nbr = []
for neighb in atom.GetNeighbors():
nbr.append(neighb)
for bond in atom.GetBonds():
mol.RemoveBond(bond.GetBeginAtomIdx(), bond.GetEndAtomIdx())
mol.RemoveAtom(atom.GetIdx())
n1 = nbr.pop(random.randrange(0, 4, 1))
if random.random() < 0.75: #XA4 -> A-A-A-A
n2 = nbr.pop(random.randrange(0, 3, 1))
mol.AddBond(n1.GetIdx(), n2.GetIdx(), bondorder[1])
n3 = nbr.pop(random.randrange(0, 2, 1))
mol.AddBond(n2.GetIdx(), n3.GetIdx(), bondorder[1])
mol.AddBond(n3.GetIdx(), nbr[0].GetIdx(), bondorder[1])
else: #XA4 -> A(A3)
for neighb in nbr:
mol.AddBond(n1.GetIdx(), neighb.GetIdx(), bondorder[1])
#Make sure nothing is bonded twice
oldpairs = []
todelete = []
for bond in mol.GetBonds():
pair = [bond.GetBeginAtomIdx(), bond.GetEndAtomIdx()]
pair.sort()
if pair in oldpairs: todelete.append(bond)
else: oldpairs.append(pair)
for bond in todelete:
mol.RemoveBond(bond.GetIdx())
# Make sure bonding makes sense
for atom in mol.GetAtoms():
try:
if EmptyValence(atom) < 0:
for bond in atom.GetBonds():
if not bond.HasProp('group'):
bond.SetBondType(bondorder[1])
if EmptyValence(atom) < 0: raise MutateFail(mol)
except KeyError:
raise MutateFail(mol)
try:
Finalize(mol, aromatic=False)
except Exception as e:
print "in Remove Atom with:", Chem.MolToSmiles(mol, True), e
return mol
def Crossover(m1, m2):
#Kekulize mols:
for m in (m1, m2):
Chem.Kekulize(m, True)
#Fragment molecules
m1fs = GetFragment(m1)
m2fs = GetFragment(m2)
if debug: print "CX1",
#print "in Crossover:", m1fs, m2fs
#pick fragments for crossover checking:
# 1. Molecular weight
Choices = []
#maxWeight = mprms.maxWeight
if maxWeight > 0:
w1 = [Descriptors.MolWt(f) for f in m1fs]
w2 = [Descriptors.MolWt(f) for f in m2fs]
for i, j in ((i, j) for i in xrange(2) for j in xrange(2)):
if w1[i] + w2[j] < maxWeight + 50.0: Choices.append((i, j))
# 2. Number of Atoms
#MxAtm=mprms.MxAtm
if MxAtm > 0:
a1 = [f.GetNumAtoms() for f in m1fs]
a2 = [f.GetNumAtoms() for f in m2fs]
for i, j in ((i, j) for i in xrange(2) for j in xrange(2)):
if a1[i] + a2[j] < MxAtm + 4: Choices.append((i, j))
if len(Choices) == 0:
raise MutateFail()
else:
choice = random.choice(Choices)
mol1 = m1fs[choice[0]]
mol2 = m2fs[choice[1]]
# now mol2 has to be connected to mol1
# but what happens here?
mol1.SetProp('parent1', m1.GetProp('isosmi'))
mol2.SetProp('parent2', m2.GetProp('isosmi'))
if debug: print "CX2",
'''
if mol1.HasProp('groups'):
m1groups=[ groupid for groupid in mol1.GetProp('groups')
if len(MolAtIsInGroup(mol1, groupid))>0 ]
mol1.ClearProp('groups')
else:
m1groups=[]
igrp=1
if mol2.HasProp('groups'):
for groupnum in mol2.GetProp('groups'):
m2groups=mol2.GetProp('groups')
if len(MolAtIsInGroup(mol2, groupnum))==0: continue
if groupnum in m1groups: #need to reassign group id
while igrp in m1groups+m2groups: igrp+=1
m1groups.append(igrp)
for atom in MolAtIsInGroup(mol2, groupnum):
atom.SetProp('group',igrp)
for bond in MolBondIsInGroup(mol2, groupnum):
bond.SetProp('group',igrp)
m2groups.append(igrp)
m2groups.remove(groupnum)
else:
m1groups.append(groupnum)
if len(m2groups)>0: mol2.SetProp('groups',m2groups)
if len(m1groups)>0: mol1.SetProp('groups',m1groups)
'''
###################################
#Append molecule 2 to molecule 1.
newmol = Chem.CombineMols(mol1, mol2)
newids = Chem.GetMolFrags(newmol)
# Now, bond the two fragments to create the child molecule.
# We choose a random pair of possible atoms to do the attachment;
possibleA1 = [
atom for atom in GetIAtoms(newids[0], newmol) if EmptyValence(atom) > 0
]
possibleA2 = [
atom for atom in GetIAtoms(newids[1], newmol) if EmptyValence(atom) > 0
]
if len(possibleA1) == 0 or len(possibleA2) == 0:
#print "no possible atoms!"
raise MutateFail()
if debug: print "CX3",
newmolRW = Chem.RWMol(newmol)
atom1 = random.choice(possibleA1)
atom2 = random.choice(possibleA2)
newmolRW.AddBond(atom1.GetIdx(), atom2.GetIdx(), Chem.BondType.SINGLE)
if debug: print "CX4",
#print "new mol!", Chem.MolToSmiles(newmolRW)
mol = newmolRW.GetMol()
try:
Finalize(mol, aromatic=False)
except:
raise MutateFail()
if debug: print "CX5",
return mol
def DelAtom(mol):
inismi = Chem.MolToSmiles(mol)
atoms = filter(CanRemoveAtom, mol.GetAtoms())
if len(atoms) == 1:
raise MutateFail()
atom = random.choice(atoms)
# or GetTotalDegree?
#Degree = atom.GetDegree() + atom.GetNumRadicalElectrons()
Degree = atom.GetDegree()
#If there's only one atom, refuse to remove it
if len(atom.GetNeighbors()) == 0:
raise MutateFail(mol)
#Remove a terminal atom:
elif Degree == 1:
for bond in atom.GetBonds():
mol.RemoveBond(bond.GetBeginAtomIdx(), bond.GetEndAtomIdx())
mol.RemoveAtom(atom.GetIdx())
# until here it seems fine
#Remove an in-chain atom:
#
#NOT WORKING WELL
elif Degree == 2:
#print Chem.MolToSmiles(mol, True)
nbr = []
for neighb in atom.GetNeighbors():
nbr.append(neighb)
for bond in atom.GetBonds():
mol.RemoveBond(bond.GetBeginAtomIdx(), bond.GetEndAtomIdx())
mol.RemoveAtom(atom.GetIdx())
# this line give indexerrors:
mol.AddBond(nbr[0].GetIdx(), nbr[1].GetIdx(), bondorder[1])
elif True:
pass
#Remove a 3-bond atom:
elif Degree == 3:
nbr = []
nbrCarbon = []
nChoice = 3
for neighb in atom.GetNeighbors():
nbr.append(neighb)
if neighb.GetAtomicNum()==6 and \
len(neighb.GetNeighbors())==3:
nChoice = nChoice + 1
nbrCarbon.append(neighb)
choose = random.randrange(0, nChoice, 1)
for bond in atom.GetBonds():
mol.RemoveBond(bond.GetBeginAtomIdx(), bond.GetBeginAtomIdx())
mol.RemoveAtom(atom.GetIdx())
if choose == 0:
mol.AddBond(nbr[0].GetIdx(), nbr[1].GetIdx(), bondorder[1])
mol.AddBond(nbr[1].GetIdx(), nbr[2].GetIdx(), bondorder[1])
elif choose == 1:
mol.AddBond(nbr[0].GetIdx(), nbr[2].GetIdx(), bondorder[1])
mol.AddBond(nbr[2].GetIdx(), nbr[1].GetIdx(), bondorder[1])
elif choose == 2:
mol.AddBond(nbr[0].GetIdx(), nbr[1].GetIdx(), bondorder[1])
mol.AddBond(nbr[2].GetIdx(), nbr[0].GetIdx(), bondorder[1])
else:
for neighb in nbr:
if not neighb.GetIdx() == nbrCarbon[choose - 3].GetIdx():
mol.AddBond(neighb.GetIdx(),
nbrCarbon[choose - 3].GetIdx(), bondorder[1])
#Remove a 4-bond atom
elif Degree == 4:
nbr = []
for neighb in atom.GetNeighbors():
nbr.append(neighb)
for bond in atom.GetBonds():
mol.RemoveBond(bond.GetBeginAtomIdx(), bond.GetEndAtomIdx())
mol.RemoveAtom(atom.GetIdx())
n1 = nbr.pop(random.randrange(0, 4, 1))
if random.random() < 0.75: #XA4 -> A-A-A-A
n2 = nbr.pop(random.randrange(0, 3, 1))
mol.AddBond(n1.GetIdx(), n2.GetIdx(), bondorder[1])
n3 = nbr.pop(random.randrange(0, 2, 1))
mol.AddBond(n2.GetIdx(), n3.GetIdx(), bondorder[1])
mol.AddBond(n3.GetIdx(), nbr[0].GetIdx(), bondorder[1])
else: #XA4 -> A(A3)
for neighb in nbr:
mol.AddBond(n1.GetIdx(), neighb.GetIdx(), bondorder[1])
#Make sure nothing is bonded twice
oldpairs = []
todelete = []
for bond in mol.GetBonds():
pair = [bond.GetBeginAtomIdx(), bond.GetEndAtomIdx()]
pair.sort()
if pair in oldpairs: todelete.append(bond)
else: oldpairs.append(pair)
for bond in todelete:
mol.RemoveBond(bond.GetIdx())
# Make sure bonding makes sense
for atom in mol.GetAtoms():
try:
if EmptyValence(atom) < 0:
for bond in atom.GetBonds():
if not bond.HasProp('group'):
bond.SetBondType(bondorder[1])
if EmptyValence(atom) < 0: raise MutateFail(mol)
except KeyError:
raise MutateFail(mol)
if debug: # print a file with the results from these mutations:
with open('delatoms.smi', 'a') as f:
f.write(Chem.MolToSmiles(mol) + '\n')
return mol