def ClassifyExample(self, example, appendExamples=0):
""" Classify an example by summing over the conditional probabilities
The most likely class is the one with the largest probability
"""
if appendExamples:
self._examples.append(example)
clsProb = {}
for key, prob in iteritems(self._classProbs):
clsProb[key] = prob
tmp = self._condProbs[key]
for ai in self._attrs:
if not (hasattr(self, '_useSigs') and self._useSigs):
bid = example[ai]
if self._qBounds[ai] > 0:
bid = _getBinId(bid, self._QBoundVals[ai])
else:
if example[1].GetBit(ai):
bid = 1
else:
bid = 0
clsProb[key] *= tmp[ai][bid]
mkey = -1
self.mprob = -1.0
for key, prob in iteritems(clsProb):
if (prob > self.mprob):
mkey = key
self.mprob = prob
return mkey
def ClassifyExample(self, example, appendExamples=0) :
""" Classify an example by summing over the conditional probabilities
The most likely class is the one with the largest probability
"""
if appendExamples:
self._examples.append(example)
clsProb = {}
for key,prob in iteritems(self._classProbs):
clsProb[key] = prob
tmp = self._condProbs[key]
for ai in self._attrs:
if not (hasattr(self,'_useSigs') and self._useSigs):
bid = example[ai]
if self._qBounds[ai] > 0 :
bid = _getBinId(bid, self._QBoundVals[ai])
else:
if example[1].GetBit(ai):
bid=1
else:
bid=0
clsProb[key] *= tmp[ai][bid]
mkey = -1
self.mprob = -1.0
for key,prob in iteritems(clsProb):
if (prob > self.mprob) :
mkey = key
self.mprob = prob
return mkey
def MolToMPL(mol,size=(300,300),kekulize=True, wedgeBonds=True,
imageType=None, fitImage=False, options=None, **kwargs):
""" Generates a drawing of a molecule on a matplotlib canvas
"""
if not mol:
raise ValueError('Null molecule provided')
from rdkit.Chem.Draw.mplCanvas import Canvas
canvas = Canvas(size)
if options is None:
options = DrawingOptions()
options.bgColor=None
if fitImage:
drawingOptions.dotsPerAngstrom = int(min(size) / 10)
options.wedgeDashedBonds=wedgeBonds
drawer = MolDrawing(canvas=canvas, drawingOptions=options)
omol=mol
if kekulize:
from rdkit import Chem
mol = Chem.Mol(mol.ToBinary())
Chem.Kekulize(mol)
if not mol.GetNumConformers():
from rdkit.Chem import AllChem
AllChem.Compute2DCoords(mol)
drawer.AddMol(mol,**kwargs)
omol._atomPs=drawer.atomPs[mol]
for k,v in iteritems(omol._atomPs):
omol._atomPs[k]=canvas.rescalePt(v)
canvas._figure.set_size_inches(float(size[0])/100,float(size[1])/100)
return canvas._figure
def MolToMPL(mol,size=(300,300),kekulize=True, wedgeBonds=True,
imageType=None, fitImage=False, options=None, **kwargs):
""" Generates a drawing of a molecule on a matplotlib canvas
"""
if not mol:
raise ValueError('Null molecule provided')
from rdkit.Chem.Draw.mplCanvas import Canvas
canvas = Canvas(size)
if options is None:
options = DrawingOptions()
options.bgColor=None
if fitImage:
drawingOptions.dotsPerAngstrom = int(min(size) / 10)
options.wedgeDashedBonds=wedgeBonds
drawer = MolDrawing(canvas=canvas, drawingOptions=options)
omol=mol
if kekulize:
from rdkit import Chem
mol = Chem.Mol(mol.ToBinary())
Chem.Kekulize(mol)
if not mol.GetNumConformers():
from rdkit.Chem import AllChem
AllChem.Compute2DCoords(mol)
drawer.AddMol(mol,**kwargs)
omol._atomPs=drawer.atomPs[mol]
for k,v in iteritems(omol._atomPs):
omol._atomPs[k]=canvas.rescalePt(v)
canvas._figure.set_size_inches(float(size[0])/100,float(size[1])/100)
return canvas._figure
def GetAllChildren(self):
" returns a dictionary, keyed by SMILES, of children "
res = {}
for smi, child in iteritems(self.children):
res[smi] = child
child._gacRecurse(res, terminalOnly=False)
return res
def GetAllChildren(self):
" returns a dictionary, keyed by SMILES, of children "
res = {}
for smi,child in iteritems(self.children):
res[smi] = child
child._gacRecurse(res,terminalOnly=False)
return res
def calculateSAScore(m, fscores):
# fragment score
fp = rdMolDescriptors.GetMorganFingerprint(m, 2)
fps = fp.GetNonzeroElements()
score1 = 0.
nf = 0
for bitId, v in iteritems(fps):
nf += v
sfp = bitId
score1 += fscores.get(sfp, -4) * v
score1 /= nf
# features score
nAtoms = m.GetNumAtoms()
nChiralCenters = len(Chem.FindMolChiralCenters(m, includeUnassigned=True))
ri = m.GetRingInfo()
nBridgeheads, nSpiro = numBridgeheadsAndSpiro(m, ri)
nMacrocycles = 0
for x in ri.AtomRings():
if len(x) > 8:
nMacrocycles += 1
sizePenalty = nAtoms**1.005 - nAtoms
stereoPenalty = math.log10(nChiralCenters + 1)
spiroPenalty = math.log10(nSpiro + 1)
bridgePenalty = math.log10(nBridgeheads + 1)
macrocyclePenalty = 0.
# ---------------------------------------
# This differs from the paper, which defines:
# macrocyclePenalty = math.log10(nMacrocycles+1)
# This form generates better results when 2 or more macrocycles are present
if nMacrocycles > 0:
macrocyclePenalty = math.log10(2)
score2 = 0. - sizePenalty - stereoPenalty - spiroPenalty - \
bridgePenalty - macrocyclePenalty
# correction for the fingerprint density
# not in the original publication, added in version 1.1
# to make highly symmetrical molecules easier to synthetise
score3 = 0.
if nAtoms > len(fps):
score3 = math.log(float(nAtoms) / len(fps)) * .5
sascore = score1 + score2 + score3
# need to transform "raw" value into scale between 1 and 10
min = -4.0
max = 2.5
sascore = 11. - (sascore - min + 1) / (max - min) * 9.
# smooth the 10-end
if sascore > 8.:
sascore = 8. + math.log(sascore + 1. - 9.)
if sascore > 10.:
sascore = 10.0
elif sascore < 1.:
sascore = 1.0
return sascore
def GetLeaves(self):
" returns a dictionary, keyed by SMILES, of leaf (terminal) nodes "
res = {}
for smi,child in iteritems(self.children):
if not len(child.children):
res[smi] = child
else:
child._gacRecurse(res,terminalOnly=True)
return res
def GetLeaves(self):
" returns a dictionary, keyed by SMILES, of leaf (terminal) nodes "
res = {}
for smi, child in iteritems(self.children):
if not len(child.children):
res[smi] = child
else:
child._gacRecurse(res, terminalOnly=True)
return res
def calculateScore(m):
if _fscores is None: readFragmentScores()
# fragment score
fp = rdMolDescriptors.GetMorganFingerprint(m,2) #<- 2 is the *radius* of the circular fingerprint
fps = fp.GetNonzeroElements()
score1 = 0.
nf = 0
for bitId,v in iteritems(fps):
nf += v
sfp = bitId
score1 += _fscores.get(sfp,-4)*v
score1 /= nf
# features score
nAtoms = m.GetNumAtoms()
nChiralCenters = len(Chem.FindMolChiralCenters(m,includeUnassigned=True))
ri = m.GetRingInfo()
nBridgeheads,nSpiro=numBridgeheadsAndSpiro(m,ri)
nMacrocycles=0
for x in ri.AtomRings():
if len(x)>8: nMacrocycles+=1
sizePenalty = nAtoms**1.005 - nAtoms
stereoPenalty = math.log10(nChiralCenters+1)
spiroPenalty = math.log10(nSpiro+1)
bridgePenalty = math.log10(nBridgeheads+1)
macrocyclePenalty = 0.
# ---------------------------------------
# This differs from the paper, which defines:
# macrocyclePenalty = math.log10(nMacrocycles+1)
# This form generates better results when 2 or more macrocycles are present
if nMacrocycles > 0: macrocyclePenalty = math.log10(2)
score2 = 0. -sizePenalty -stereoPenalty -spiroPenalty -bridgePenalty -macrocyclePenalty
# correction for the fingerprint density
# not in the original publication, added in version 1.1
# to make highly symmetrical molecules easier to synthetise
score3 = 0.
if nAtoms > len(fps):
score3 = math.log(float(nAtoms) / len(fps)) * .5
sascore = score1 + score2 + score3
# need to transform "raw" value into scale between 1 and 10
min = -4.0
max = 2.5
sascore = 11. - (sascore - min + 1) / (max - min) * 9.
# smooth the 10-end
if sascore > 8.: sascore = 8. + math.log(sascore+1.-9.)
if sascore > 10.: sascore = 10.0
elif sascore < 1.: sascore = 1.0
return sascore
def GetMorganFingerprint(mol, atomId=-1, radius=2, fpType='bv', nBits=2048, useFeatures=False, **kwargs):
"""
Calculates the Morgan fingerprint with the environments of atomId removed.
Parameters:
mol -- the molecule of interest
radius -- the maximum radius
fpType -- the type of Morgan fingerprint: 'count' or 'bv'
atomId -- the atom to remove the environments for (if -1, no environments is removed)
nBits -- the size of the bit vector (only for fpType = 'bv')
useFeatures -- if false: ConnectivityMorgan, if true: FeatureMorgan
any additional keyword arguments will be passed to the fingerprinting function.
"""
if fpType not in ['bv', 'count']: raise ValueError("Unknown Morgan fingerprint type")
if not hasattr(mol, '_fpInfo'):
info = {}
# get the fingerprint
if fpType == 'bv': molFp = rdMD.GetMorganFingerprintAsBitVect(mol, radius, nBits=nBits,
useFeatures=useFeatures, bitInfo=info,
**kwargs)
else: molFp = rdMD.GetMorganFingerprint(mol, radius, useFeatures=useFeatures, bitInfo=info,
**kwargs)
# construct the bit map
if fpType == 'bv': bitmap = [DataStructs.ExplicitBitVect(nBits) for x in range(mol.GetNumAtoms())]
else: bitmap = [[] for x in range(mol.GetNumAtoms())]
for bit, es in iteritems(info):
for at1, rad in es:
if rad == 0: # for radius 0
if fpType == 'bv': bitmap[at1][bit] = 1
else: bitmap[at1].append(bit)
else: # for radii > 0
env = Chem.FindAtomEnvironmentOfRadiusN(mol, rad, at1)
amap = {}
submol = Chem.PathToSubmol(mol, env, atomMap=amap)
for at2 in amap.keys():
if fpType == 'bv': bitmap[at2][bit] = 1
else: bitmap[at2].append(bit)
mol._fpInfo = (molFp, bitmap)
if atomId < 0:
return mol._fpInfo[0]
else: # remove the bits of atomId
if atomId >= mol.GetNumAtoms(): raise ValueError("atom index greater than number of atoms")
if len(mol._fpInfo) != 2: raise ValueError("_fpInfo not set")
if fpType == 'bv':
molFp = mol._fpInfo[0] ^ mol._fpInfo[1][atomId] # xor
else: # count
molFp = copy.deepcopy(mol._fpInfo[0])
# delete the bits with atomId
for bit in mol._fpInfo[1][atomId]:
molFp[bit] -= 1
return molFp
def GetMorganFingerprint(mol, atomId=-1, radius=2, fpType='bv', nBits=2048, useFeatures=False,
**kwargs):
"""
Calculates the Morgan fingerprint with the environments of atomId removed.
Parameters:
mol -- the molecule of interest
radius -- the maximum radius
fpType -- the type of Morgan fingerprint: 'count' or 'bv'
atomId -- the atom to remove the environments for (if -1, no environments is removed)
nBits -- the size of the bit vector (only for fpType = 'bv')
useFeatures -- if false: ConnectivityMorgan, if true: FeatureMorgan
any additional keyword arguments will be passed to the fingerprinting function.
"""
if fpType not in ['bv', 'count']:
raise ValueError("Unknown Morgan fingerprint type")
if not hasattr(mol, '_fpInfo'):
info = {}
# get the fingerprint
if fpType == 'bv':
molFp = rdMD.GetMorganFingerprintAsBitVect(mol, radius, nBits=nBits, useFeatures=useFeatures,
bitInfo=info, **kwargs)
else:
molFp = rdMD.GetMorganFingerprint(mol, radius, useFeatures=useFeatures, bitInfo=info,
**kwargs)
# construct the bit map
if fpType == 'bv':
bitmap = [DataStructs.ExplicitBitVect(nBits) for x in range(mol.GetNumAtoms())]
else:
bitmap = [[] for x in range(mol.GetNumAtoms())]
for bit, es in iteritems(info):
for at1, rad in es:
if rad == 0: # for radius 0
if fpType == 'bv':
bitmap[at1][bit] = 1
else:
bitmap[at1].append(bit)
else: # for radii > 0
env = Chem.FindAtomEnvironmentOfRadiusN(mol, rad, at1)
amap = {}
submol = Chem.PathToSubmol(mol, env, atomMap=amap)
for at2 in amap.keys():
if fpType == 'bv':
bitmap[at2][bit] = 1
else:
bitmap[at2].append(bit)
mol._fpInfo = (molFp, bitmap)
if atomId < 0:
return mol._fpInfo[0]
else: # remove the bits of atomId
if atomId >= mol.GetNumAtoms():
raise ValueError("atom index greater than number of atoms")
if len(mol._fpInfo) != 2:
raise ValueError("_fpInfo not set")
if fpType == 'bv':
molFp = mol._fpInfo[0] ^ mol._fpInfo[1][atomId] # xor
else: # count
molFp = copy.deepcopy(mol._fpInfo[0])
# delete the bits with atomId
for bit in mol._fpInfo[1][atomId]:
molFp[bit] -= 1
return molFp
g2 = re.sub('[a-z,A-Z]', '', g2)
sma = '[$(%s):1]%s;!@[$(%s):2]>>[%s*]-[*:1].[%s*]-[*:2]' % (r1, bnd,
r2, g1, g2)
gp[j] = sma
for gp in smartsGps:
for defn in gp:
try:
t = Reactions.ReactionFromSmarts(defn)
t.Initialize()
except Exception:
print(defn)
raise
environMatchers = {}
for env, sma in iteritems(environs):
environMatchers[env] = Chem.MolFromSmarts(sma)
bondMatchers = []
for i, compats in enumerate(reactionDefs):
tmp = []
for i1, i2, bType in compats:
e1 = environs['L%s' % i1]
e2 = environs['L%s' % i2]
patt = '[$(%s)]%s;!@[$(%s)]' % (e1, bType, e2)
patt = Chem.MolFromSmarts(patt)
tmp.append((i1, i2, bType, patt))
bondMatchers.append(tmp)
reactions = tuple([[Reactions.ReactionFromSmarts(y) for y in x]
for x in smartsGps])
def FindBRICSBonds(mol, randomizeOrder=False, silent=True):
""" returns the bonds in a molecule that BRICS would cleave
>>> from rdkit import Chem
>>> m = Chem.MolFromSmiles('CCCOCC')
>>> res = list(FindBRICSBonds(m))
>>> res
[((3, 2), ('3', '4')), ((3, 4), ('3', '4'))]
a more complicated case:
>>> m = Chem.MolFromSmiles('CCCOCCC(=O)c1ccccc1')
>>> res = list(FindBRICSBonds(m))
>>> res
[((3, 2), ('3', '4')), ((3, 4), ('3', '4')), ((6, 8), ('6', '16'))]
we can also randomize the order of the results:
>>> random.seed(23)
>>> res = list(FindBRICSBonds(m,randomizeOrder=True))
>>> sorted(res)
[((3, 2), ('3', '4')), ((3, 4), ('3', '4')), ((6, 8), ('6', '16'))]
Note that this is a generator function :
>>> res = FindBRICSBonds(m)
>>> res
<generator object ...>
>>> next(res)
((3, 2), ('3', '4'))
>>> m = Chem.MolFromSmiles('CC=CC')
>>> res = list(FindBRICSBonds(m))
>>> sorted(res)
[((1, 2), ('7', '7'))]
make sure we don't match ring bonds:
>>> m = Chem.MolFromSmiles('O=C1NCCC1')
>>> list(FindBRICSBonds(m))
[]
another nice one, make sure environment 8 doesn't match something connected
to a ring atom:
>>> m = Chem.MolFromSmiles('CC1(C)CCCCC1')
>>> list(FindBRICSBonds(m))
[]
"""
letter = re.compile('[a-z,A-Z]')
indices = list(range(len(bondMatchers)))
bondsDone = set()
if randomizeOrder:
random.shuffle(indices, random=random.random)
envMatches = {}
for env, patt in iteritems(environMatchers):
envMatches[env] = mol.HasSubstructMatch(patt)
for gpIdx in indices:
if randomizeOrder:
compats = bondMatchers[gpIdx][:]
random.shuffle(compats, random=random.random)
else:
compats = bondMatchers[gpIdx]
for i1, i2, bType, patt in compats:
if not envMatches['L' + i1] or not envMatches['L' + i2]:
continue
matches = mol.GetSubstructMatches(patt)
i1 = letter.sub('', i1)
i2 = letter.sub('', i2)
for match in matches:
if match not in bondsDone and (match[1],
match[0]) not in bondsDone:
bondsDone.add(match)
yield (((match[0], match[1]), (i1, i2)))
def calculate_score(m):
if _fscores is None:
read_fragment_scores()
# fragment score
fp = rdMolDescriptors.GetMorganFingerprint(m, 2) # <- 2 is the *radius* of the circular fingerprint
fps = fp.GetNonzeroElements()
score1 = 0.
nf = 0
for bitId, v in iteritems(fps):
nf += v
sfp = bitId
score1 += _fscores.get(sfp, -4) * v
score1 /= nf
# features score
n_atoms = m.GetNumAtoms()
n_chiral_centers = len(Chem.FindMolChiralCenters(m, includeUnassigned=True))
ri = m.GetRingInfo()
n_bridgeheads, n_spiro = num_bridgeheads_and_spiro(m)
n_macrocycles = 0
for x in ri.AtomRings():
if len(x) > 8:
n_macrocycles += 1
size_penalty = n_atoms ** 1.005 - n_atoms
stereo_penalty = math.log10(n_chiral_centers + 1)
spiro_penalty = math.log10(n_spiro + 1)
bridge_penalty = math.log10(n_bridgeheads + 1)
macrocycle_penalty = 0.
# ---------------------------------------
# This differs from the paper, which defines:
# macrocycle_penalty = math.log10(n_macrocycles+1)
# This form generates better results when 2 or more macrocycles are present
if n_macrocycles > 0:
macrocycle_penalty = math.log10(2)
score2 = 0. - size_penalty - stereo_penalty - spiro_penalty - bridge_penalty - macrocycle_penalty
# correction for the fingerprint density
# not in the original publication, added in version 1.1
# to make highly symmetrical molecules easier to synthetise
score3 = 0.
if n_atoms > len(fps):
score3 = math.log(float(n_atoms) / len(fps)) * .5
sascore = score1 + score2 + score3
# need to transform "raw" value into scale between 1 and 10
minimum = -4.0
maximum = 2.5
sascore = 11. - (sascore - minimum + 1) / (maximum - minimum) * 9.
# smooth the 10-end
if sascore > 8.:
sascore = 8. + math.log(sascore + 1. - 9.)
if sascore > 10.:
sascore = 10.0
elif sascore < 1.:
sascore = 1.0
return sascore
def FindBRICSBonds(mol,randomizeOrder=False,silent=True):
""" returns the bonds in a molecule that BRICS would cleave
>>> from rdkit import Chem
>>> m = Chem.MolFromSmiles('CCCOCC')
>>> res = list(FindBRICSBonds(m))
>>> res
[((3, 2), ('3', '4')), ((3, 4), ('3', '4'))]
a more complicated case:
>>> m = Chem.MolFromSmiles('CCCOCCC(=O)c1ccccc1')
>>> res = list(FindBRICSBonds(m))
>>> res
[((3, 2), ('3', '4')), ((3, 4), ('3', '4')), ((6, 8), ('6', '16'))]
we can also randomize the order of the results:
>>> random.seed(23)
>>> res = list(FindBRICSBonds(m,randomizeOrder=True))
>>> sorted(res)
[((3, 2), ('3', '4')), ((3, 4), ('3', '4')), ((6, 8), ('6', '16'))]
Note that this is a generator function :
>>> res = FindBRICSBonds(m)
>>> res
<generator object ...>
>>> next(res)
((3, 2), ('3', '4'))
>>> m = Chem.MolFromSmiles('CC=CC')
>>> res = list(FindBRICSBonds(m))
>>> sorted(res)
[((1, 2), ('7', '7'))]
make sure we don't match ring bonds:
>>> m = Chem.MolFromSmiles('O=C1NCCC1')
>>> list(FindBRICSBonds(m))
[]
another nice one, make sure environment 8 doesn't match something connected
to a ring atom:
>>> m = Chem.MolFromSmiles('CC1(C)CCCCC1')
>>> list(FindBRICSBonds(m))
[]
"""
letter = re.compile('[a-z,A-Z]')
indices = list(range(len(bondMatchers)))
bondsDone=set()
if randomizeOrder: random.shuffle(indices,random=random.random)
envMatches={}
for env,patt in iteritems(environMatchers):
envMatches[env]=mol.HasSubstructMatch(patt)
for gpIdx in indices:
if randomizeOrder:
compats =bondMatchers[gpIdx][:]
random.shuffle(compats,random=random.random)
else:
compats = bondMatchers[gpIdx]
for i1,i2,bType,patt in compats:
if not envMatches['L'+i1] or not envMatches['L'+i2]: continue
matches = mol.GetSubstructMatches(patt)
i1 = letter.sub('',i1)
i2 = letter.sub('',i2)
for match in matches:
if match not in bondsDone and (match[1],match[0]) not in bondsDone:
bondsDone.add(match)
yield(((match[0],match[1]),(i1,i2)))
def __call__(self, smile):
if _fscores is None:
self.readFragmentScores()
m = Chem.MolFromSmiles(smile)
if m:
try:
# fragment score
fp = rdMolDescriptors.GetMorganFingerprint(
m, 2) #<- 2 is the *radius* of the circular fingerprint
fps = fp.GetNonzeroElements()
score1 = 0.
nf = 0
for bitId, v in iteritems(fps):
nf += v
sfp = bitId
score1 += _fscores.get(sfp, -4) * v
score1 /= nf
# features score
nAtoms = m.GetNumAtoms()
nChiralCenters = len(
Chem.FindMolChiralCenters(m, includeUnassigned=True))
ri = m.GetRingInfo()
nBridgeheads = rdMolDescriptors.CalcNumBridgeheadAtoms(m)
nSpiro = nSpiro = rdMolDescriptors.CalcNumSpiroAtoms(m)
nMacrocycles = 0
for x in ri.AtomRings():
if len(x) > 8:
nMacrocycles += 1
sizePenalty = nAtoms**1.005 - nAtoms
stereoPenalty = math.log10(nChiralCenters + 1)
spiroPenalty = math.log10(nSpiro + 1)
bridgePenalty = math.log10(nBridgeheads + 1)
macrocyclePenalty = 0.
# ---------------------------------------
# This differs from the paper, which defines:
# macrocyclePenalty = math.log10(nMacrocycles+1)
# This form generates better results when 2 or more macrocycles are present
if nMacrocycles > 0:
macrocyclePenalty = math.log10(2)
score2 = 0. - sizePenalty - stereoPenalty - spiroPenalty - bridgePenalty - macrocyclePenalty
# correction for the fingerprint density
# not in the original publication, added in version 1.1
# to make highly symmetrical molecules easier to synthetise
score3 = 0.
if nAtoms > len(fps):
score3 = math.log(float(nAtoms) / len(fps)) * .5
sascore = score1 + score2 + score3
# need to transform "raw" value into scale between 1 and 10
min_score = -4.0
max_score = 2.5
sascore = 11. - (sascore - min_score + 1) / (max_score -
min_score) * 9.
# smooth the 10-end
if sascore > 8.: sascore = 8. + math.log(sascore + 1. - 9.)
if sascore > 10.: sascore = 10.0
elif sascore < 1.: sascore = 1.0
sascore = math.exp(1 - sascore) # minimize the sascore
return sascore
except:
return 0.0
else:
return 0.0
def _gacRecurse(self, res, terminalOnly=False):
for smi, child in iteritems(self.children):
if not terminalOnly or not len(child.children):
res[smi] = child
child._gacRecurse(res, terminalOnly=terminalOnly)
def CalcSAScore(rmol):
if _fscores is None:
ReadFragScores()
mol = copy.deepcopy(rmol)
#Chem.SanitizeMol(mol) # gives crashes!
#fragment score
fp = AllChem.GetMorganFingerprint(
mol, 2) #<- 2 is the *radius* of the circular fingerprint
fps = fp.GetNonzeroElements()
score1 = 0.0
nf = 0
for bitId, v in iteritems(fps):
nf += v
sfp = bitId
score1 += _fscores.get(sfp, -4) * v
score1 /= nf
#features score
nAtoms = mol.GetNumAtoms()
nChiralCenters = len(Chem.FindMolChiralCenters(mol,
includeUnassigned=True))
ri = mol.GetRingInfo()
nBridgehead, nSpiro = NumBridgeheadsAndSpiro(mol, ri)
nMacrocycles = 0
for x in ri.AtomRings():
if len(x) > 8:
nMacrocycles += 1
sizePenalty = nAtoms**1.005 - nAtoms
stereoPenalty = math.log10(nChiralCenters + 1)
spiroPenalty = math.log10(nSpiro + 1)
bridgePenalty = math.log10(nBridgehead + 1)
macrocyclePenalty = 0.0
# -----------------------------
# This differs from the paper, which defines:
# macrocyclePenalty = math.log10(nMacrocycles+1)
# This form generates better results when 2 or more macrocycles are present
if nMacrocycles > 0:
macrocyclePenalty = math.log10(2)
score2 = 0.0 - sizePenalty - stereoPenalty - spiroPenalty - bridgePenalty - macrocyclePenalty
# correction for the fingerprint density
# not in the original publication
# to make highly symmetrical molecules easier to synthesize
score3 = 0.0
if nAtoms > len(fps):
score3 = math.log(float(nAtoms) / len(fps)) * 0.5
sascore = score1 + score2 + score3
# need to transform "raw" value into scale between 1 and 10
minv = -4.0
maxv = 2.5
sascore = 11.0 - (sascore - minv + 1) / (maxv - minv) * 9.0
# smooth the 10-end
if sascore > 8.0:
sascore = 8.0 + math.log(sascore - 8.0)
if sascore > 10.0:
sascore = 10.0
elif sascore < 1.0:
sascore = 1.0
return sascore
def _gacRecurse(self,res,terminalOnly=False):
for smi,child in iteritems(self.children):
if not terminalOnly or not len(child.children):
res[smi] = child
child._gacRecurse(res,terminalOnly=terminalOnly)
g1 = re.sub('[a-z,A-Z]','',g1)
g2 = re.sub('[a-z,A-Z]','',g2)
sma='[$(%s):1]%s;!@[$(%s):2]>>[%s*]-[*:1].[%s*]-[*:2]'%(r1,bnd,r2,g1,g2)
gp[j] =sma
for gp in smartsGps:
for defn in gp:
try:
t=Reactions.ReactionFromSmarts(defn)
t.Initialize()
except:
print(defn)
raise
environMatchers={}
for env,sma in iteritems(environs):
environMatchers[env]=Chem.MolFromSmarts(sma)
bondMatchers=[]
for i,compats in enumerate(reactionDefs):
tmp=[]
for i1,i2,bType in compats:
e1 = environs['L%s'%i1]
e2 = environs['L%s'%i2]
patt = '[$(%s)]%s;!@[$(%s)]'%(e1,bType,e2)
patt = Chem.MolFromSmarts(patt)
tmp.append((i1,i2,bType,patt))
bondMatchers.append(tmp)
reactions = tuple([[Reactions.ReactionFromSmarts(y) for y in x] for x in smartsGps])
reverseReactions = []
def synthetic_accessibility(mol, _fscores=None):
'''
calculation of synthetic accessibility score as described in:
'Estimation of Synthetic Accessibility Score of Drug-like Molecules
based on Molecular Complexity and Fragment Contributions'
Peter Ertl and Ansgar Schuffenhauer
Journal of Cheminformatics 1:8 (2009)
http://www.jcheminf.com/content/1/1/8
several small modifications to the original paper are included
particularly slightly different formula for marocyclic penalty
and taking into account also molecule symmetry (fingerprint density)
for a set of 10k diverse molecules the agreement between the original method
as implemented in PipelinePilot and this implementation is r2 = 0.97
peter ertl & greg landrum, september 2013
Parameters
----------
mol : Mol
Returns
-------
float : synthetic accessibility score
'''
if _fscores is None:
with gzip.open(os.path.join(os.path.dirname(__file__), 'fpscores.pkl.gz'), 'rb') as f:
_fscores = pickle.load(f)
out_dict = {}
for each_list in _fscores:
for each_idx in range(1,len(each_list)):
out_dict[each_list[each_idx]] = float(each_list[0])
_fscores = out_dict
# fragment score
# 2 is the *radius* of the circular fingerprint
fingerprint = rdMolDescriptors.GetMorganFingerprint(mol, 2)
fingerprints = fingerprint.GetNonzeroElements()
score1 = 0.
nf = 0
for bit_id, value in iteritems(fingerprints):
nf += value
sfp = bit_id
score1 += _fscores.get(sfp, -4) * value
score1 /= nf
# features score
num_atoms = mol.GetNumAtoms()
num_chiral_centers = len(Chem.FindMolChiralCenters(mol, includeUnassigned=True))
ring_info = mol.GetRingInfo()
num_spiro = rdMolDescriptors.CalcNumSpiroAtoms(mol)
num_bridgeheads = rdMolDescriptors.CalcNumBridgeheadAtoms(mol)
num_macrocycles = 0
for each_ring in ring_info.AtomRings():
if len(each_ring) > 8:
num_macrocycles += 1
size_penalty = num_atoms ** 1.005 - num_atoms
stereo_penalty = math.log10(num_chiral_centers + 1)
spiro_penalty = math.log10(num_spiro + 1)
bridge_penalty = math.log10(num_bridgeheads + 1)
macrocycle_penalty = 0.
# ---------------------------------------
# This differs from the paper, which defines:
# macrocycle_penalty = math.log10(num_macrocycles+1)
# This form generates better results when 2 or more macrocycles are present
if num_macrocycles > 0:
macrocycle_penalty = math.log10(2)
score2 = 0. -size_penalty -stereo_penalty -spiro_penalty -bridge_penalty -macrocycle_penalty
# correction for the fingerprint density
# not in the original publication, added in version 1.1
# to make highly symmetrical molecules easier to synthetise
score3 = 0.
if num_atoms > len(fingerprints):
score3 = math.log(float(num_atoms) / len(fingerprints)) * .5
sascore = score1 + score2 + score3
# need to transform "raw" value into scale between 1 and 10
min_score = -4.0
max_score = 2.5
sascore = 11. - (sascore - min_score + 1) / (max_score - min_score) * 9.
# smooth the 10-end
if sascore > 8.:
sascore = 8. + math.log(sascore+1.-9.)
if sascore > 10.:
sascore = 10.0
elif sascore < 1.:
sascore = 1.0
return sascore