Package rdkit :: Package Chem :: Module MolSurf

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# Source Code for Module rdkit.Chem.MolSurf

      1  # $Id$
      2  #
      3  # Copyright (C) 2001-2008 greg Landrum and Rational Discovery LLC
      4  #
      5  #   @@ All Rights Reserved @@
      6  #  This file is part of the RDKit.
      7  #  The contents are covered by the terms of the BSD license
      8  #  which is included in the file license.txt, found at the root
      9  #  of the RDKit source tree.
     10  #
     11  """ Exposes functionality for MOE-like approximate molecular surface area
     12  descriptors.
     13
     14    The MOE-like VSA descriptors are also calculated here
     15
     16  """
     17  from __future__ import print_function
     18  from rdkit import Chem
     19  from rdkit.Chem.PeriodicTable import numTable
     20  from rdkit.Chem import Crippen
     21  from rdkit.Chem import rdPartialCharges,rdMolDescriptors
     22  import numpy
     23  import bisect
     24  radCol = 5
     25  bondScaleFacts = [ .1,0,.2,.3] # aromatic,single,double,triple
     26
     27 -def _LabuteHelper(mol,includeHs=1,force=0):
     28    """ *Internal Use Only*
     29      helper function for LabuteASA calculation
     30      returns an array of atomic contributions to the ASA
     31
     32    **Note:** Changes here affect the version numbers of all ASA descriptors
     33
     34    """
     35    if not force:
     36      try:
     37        res = mol._labuteContribs
     38      except AttributeError:
     39        pass
     40      else:
     41        if res:
     42          return res
     43    tpl = rdMolDescriptors._CalcLabuteASAContribs(mol,includeHs)
     44    ats,hs=tpl
     45    Vi=[hs]+list(ats)
     46    mol._labuteContribs=Vi
     47    return Vi
     48 -def _pyLabuteHelper(mol,includeHs=1,force=0):
     49    """ *Internal Use Only*
     50      helper function for LabuteASA calculation
     51      returns an array of atomic contributions to the ASA
     52
     53    **Note:** Changes here affect the version numbers of all ASA descriptors
     54
     55    """
     56    import math
     57    if not force:
     58      try:
     59        res = mol._labuteContribs
     60      except AttributeError:
     61        pass
     62      else:
     63        if res.all():
     64          return res
     65
     66    nAts = mol.GetNumAtoms()
     67    Vi = numpy.zeros(nAts+1,'d')
     68    rads = numpy.zeros(nAts+1,'d')
     69
     70    # 0 contains the H information
     71    rads[0] = numTable[1][radCol]
     72    for i in xrange(nAts):
     73      rads[i+1] = numTable[mol.GetAtomWithIdx(i).GetAtomicNum()][radCol]
     74
     75    # start with explicit bonds
     76    for bond in mol.GetBonds():
     77      idx1 = bond.GetBeginAtomIdx()+1
     78      idx2 = bond.GetEndAtomIdx()+1
     79      Ri = rads[idx1]
     80      Rj = rads[idx2]
     81
     82      if not bond.GetIsAromatic():
     83        bij = Ri+Rj - bondScaleFacts[bond.GetBondType()]
     84      else:
     85        bij = Ri+Rj - bondScaleFacts[0]
     86      dij = min( max( abs(Ri-Rj), bij), Ri+Rj)
     87      Vi[idx1] += Rj*Rj - (Ri-dij)**2 / dij
     88      Vi[idx2] += Ri*Ri - (Rj-dij)**2 / dij
     89
     90    # add in hydrogens
     91    if includeHs:
     92      j = 0
     93      Rj = rads[j]
     94      for i in xrange(1,nAts+1):
     95        Ri = rads[i]
     96        bij = Ri+Rj
     97        dij = min( max( abs(Ri-Rj), bij), Ri+Rj)
     98        Vi[i] += Rj*Rj - (Ri-dij)**2 / dij
     99        Vi[j] += Ri*Ri - (Rj-dij)**2 / dij
    100
    101    for i in xrange(nAts+1):
    102      Ri = rads[i]
    103      Vi[i] = 4*math.pi * Ri**2 - math.pi * Ri * Vi[i]
    104
    105    mol._labuteContribs=Vi
    106    return Vi
    107
    108  #def SMR_VSA(mol,bins=[0.11,0.26,0.35,0.39,0.44,0.485,0.56]):
    109  # original default bins from assuming Labute values are logs
    110  # mrBins=[1.29, 1.82, 2.24, 2.45, 2.75, 3.05, 3.63]
    111  mrBins=[1.29, 1.82, 2.24, 2.45, 2.75, 3.05, 3.63,3.8,4.0]
    112 -def pySMR_VSA_(mol,bins=None,force=1):
    113    """ *Internal Use Only*
    114    """
    115    if not force:
    116      try:
    117        res = mol._smrVSA
    118      except AttributeError:
    119        pass
    120      else:
    121        if res.all():
    122          return res
    123
    124    if bins is None: bins = mrBins
    125    Crippen._Init()
    126    propContribs = Crippen._GetAtomContribs(mol,force=force)
    127    volContribs = _LabuteHelper(mol)
    128
    129    ans = numpy.zeros(len(bins)+1,'d')
    130    for i in range(len(propContribs)):
    131      prop = propContribs[i]
    132      vol = volContribs[i+1]
    133      if prop is not None:
    134        bin = bisect.bisect_right(bins,prop[1])
    135        ans[bin] += vol
    136
    137    mol._smrVSA=ans
    138    return ans
    139  SMR_VSA_ = rdMolDescriptors.SMR_VSA_
    140
    141  #
    142  # Original bins (from Labute paper) are:
    143  #  [-0.4,-0.2,0,0.1,0.15,0.2,0.25,0.3,0.4]
    144  #
    145  logpBins=[-0.4,-0.2,0,0.1,0.15,0.2,0.25,0.3,0.4,0.5,0.6]
    146 -def pySlogP_VSA_(mol,bins=None,force=1):
    147    """ *Internal Use Only*
    148    """
    149    if not force:
    150      try:
    151        res = mol._slogpVSA
    152      except AttributeError:
    153        pass
    154      else:
    155        if res.all():
    156          return res
    157
    158    if bins is None: bins = logpBins
    159    Crippen._Init()
    160    propContribs = Crippen._GetAtomContribs(mol,force=force)
    161    volContribs = _LabuteHelper(mol)
    162
    163    ans = numpy.zeros(len(bins)+1,'d')
    164    for i in range(len(propContribs)):
    165      prop = propContribs[i]
    166      vol = volContribs[i+1]
    167      if prop is not None:
    168        bin = bisect.bisect_right(bins,prop[0])
    169        ans[bin] += vol
    170
    171    mol._slogpVSA=ans
    172    return ans
    173  SlogP_VSA_ = rdMolDescriptors.SlogP_VSA_
    174
    175  chgBins=[-.3,-.25,-.20,-.15,-.10,-.05,0,.05,.10,.15,.20,.25,.30]
    176 -def pyPEOE_VSA_(mol,bins=None,force=1):
    177    """ *Internal Use Only*
    178    """
    179    if not force:
    180      try:
    181        res = mol._peoeVSA
    182      except AttributeError:
    183        pass
    184      else:
    185        if res.all():
    186          return res
    187    if bins is None: bins = chgBins
    188    Crippen._Init()
    189    #print('\ts:',repr(mol.GetMol()))
    190    #print('\t\t:',len(mol.GetAtoms()))
    191    rdPartialCharges.ComputeGasteigerCharges(mol)
    192
    193    #propContribs = [float(x.GetProp('_GasteigerCharge'))  for x in mol.GetAtoms()]
    194    propContribs=[]
    195    for at in mol.GetAtoms():
    196      p = at.GetProp('_GasteigerCharge')
    197      try:
    198        v = float(p)
    199      except ValueError:
    200        v = 0.0
    201      propContribs.append(v)
    202    #print '\tp',propContribs
    203    volContribs = _LabuteHelper(mol)
    204    #print '\tv',volContribs
    205
    206    ans = numpy.zeros(len(bins)+1,'d')
    207    for i in range(len(propContribs)):
    208      prop = propContribs[i]
    209      vol = volContribs[i+1]
    210      if prop is not None:
    211        bin = bisect.bisect_right(bins,prop)
    212        ans[bin] += vol
    213
    214    mol._peoeVSA=ans
    215    return ans
    216  PEOE_VSA_=rdMolDescriptors.PEOE_VSA_
    217
    218  #-------------------------------------------------
    219  # install the various VSA descriptors in the namespace
    220 -def _InstallDescriptors():
    221    for i in range(len(mrBins)):
    222      fn = lambda x,y=i:SMR_VSA_(x,force=0)[y]
    223      if i > 0:
    224        fn.__doc__="MOE MR VSA Descriptor %d (% 4.2f <= x < % 4.2f)"%(i+1,mrBins[i-1],mrBins[i])
    225      else:
    226        fn.__doc__="MOE MR VSA Descriptor %d (-inf < x < % 4.2f)"%(i+1,mrBins[i])
    227      name="SMR_VSA%d"%(i+1)
    228      fn.version="1.0.1"
    229      globals()[name]=fn
    230    i+=1
    231    fn = lambda x,y=i:SMR_VSA_(x,force=0)[y]
    232    fn.__doc__="MOE MR VSA Descriptor %d (% 4.2f <= x < inf)"%(i+1,mrBins[i-1])
    233    fn.version="1.0.1"
    234    name="SMR_VSA%d"%(i+1)
    235    globals()[name]=fn
    236
    237    for i in range(len(logpBins)):
    238      fn = lambda x,y=i:SlogP_VSA_(x,force=0)[y]
    239      if i > 0:
    240        fn.__doc__="MOE logP VSA Descriptor %d (% 4.2f <= x < % 4.2f)"%(i+1,logpBins[i-1],
    241                                                                        logpBins[i])
    242      else:
    243        fn.__doc__="MOE logP VSA Descriptor %d (-inf < x < % 4.2f)"%(i+1,logpBins[i])
    244      name="SlogP_VSA%d"%(i+1)
    245      fn.version="1.0.1"
    246      globals()[name]=fn
    247    i+=1
    248    fn = lambda x,y=i:SlogP_VSA_(x,force=0)[y]
    249    fn.__doc__="MOE logP VSA Descriptor %d (% 4.2f <= x < inf)"%(i+1,logpBins[i-1])
    250    fn.version="1.0.1"
    251    name="SlogP_VSA%d"%(i+1)
    252    globals()[name]=fn
    253
    254    for i in range(len(chgBins)):
    255      fn = lambda x,y=i:PEOE_VSA_(x,force=0)[y]
    256      if i > 0:
    257        fn.__doc__="MOE Charge VSA Descriptor %d (% 4.2f <= x < % 4.2f)"%(i+1,chgBins[i-1],
    258                                                                          chgBins[i])
    259      else:
    260        fn.__doc__="MOE Charge VSA Descriptor %d (-inf < x < % 4.2f)"%(i+1,chgBins[i])
    261      name="PEOE_VSA%d"%(i+1)
    262      fn.version="1.0.1"
    263      globals()[name]=fn
    264    i+=1
    265    fn = lambda x,y=i:PEOE_VSA_(x,force=0)[y]
    266    fn.version="1.0.1"
    267    fn.__doc__="MOE Charge VSA Descriptor %d (% 4.2f <= x < inf)"%(i+1,chgBins[i-1])
    268    name="PEOE_VSA%d"%(i+1)
    269    globals()[name]=fn
    270    fn = None
    271    # Change log for the MOE-type descriptors:
    272    #  version 1.0.1: optimizations, values unaffected
    273  _InstallDescriptors()
    274
    275 -def pyLabuteASA(mol,includeHs=1):
    276    """ calculates Labute's Approximate Surface Area (ASA from MOE)
    277
    278      Definition from P. Labute's article in the Journal of the Chemical Computing Group
    279      and J. Mol. Graph. Mod.  _18_ 464-477 (2000)
    280
    281    """
    282    Vi = _LabuteHelper(mol,includeHs=includeHs)
    283    return sum(Vi)
    284  pyLabuteASA.version="1.0.1"
    285  # Change log for LabuteASA:
    286  #  version 1.0.1: optimizations, values unaffected
    287  LabuteASA=lambda *x,**y:rdMolDescriptors.CalcLabuteASA(*x,**y)
    288  LabuteASA.version=rdMolDescriptors._CalcLabuteASA_version
    289
    290
    291 -def _pyTPSAContribs(mol,verbose=False):
    292    """ DEPRECATED: this has been reimplmented in C++
    293    calculates atomic contributions to a molecules TPSA
    294
    295     Algorithm described in:
    296      P. Ertl, B. Rohde, P. Selzer
    297       Fast Calculation of Molecular Polar Surface Area as a Sum of Fragment-based
    298       Contributions and Its Application to the Prediction of Drug Transport
    299       Properties, J.Med.Chem. 43, 3714-3717, 2000
    300
    301     Implementation based on the Daylight contrib program tpsa.c
    302
    303     NOTE: The JMC paper describing the TPSA algorithm includes
    304     contributions from sulfur and phosphorus, however according to
    305     Peter Ertl (personal communication, 2010) the correlation of TPSA
    306     with various ADME properties is better if only contributions from
    307     oxygen and nitrogen are used. This matches the daylight contrib
    308     implementation.
    309
    310    """
    311    res = [0]*mol.GetNumAtoms()
    312    for i in range(mol.GetNumAtoms()):
    313      atom = mol.GetAtomWithIdx(i)
    314      atNum = atom.GetAtomicNum()
    315      if atNum in [7,8]:
    316        #nHs = atom.GetImplicitValence()-atom.GetHvyValence()
    317        nHs = atom.GetTotalNumHs()
    318        chg = atom.GetFormalCharge()
    319        isArom = atom.GetIsAromatic()
    320        in3Ring = atom.IsInRingSize(3)
    321
    322        bonds = atom.GetBonds()
    323        numNeighbors = atom.GetDegree()
    324        nSing = 0
    325        nDoub = 0
    326        nTrip = 0
    327        nArom = 0
    328        for bond in bonds:
    329          otherAt = bond.GetOtherAtom(atom)
    330          if otherAt.GetAtomicNum()!=1:
    331            if bond.GetIsAromatic():
    332              nArom += 1
    333            else:
    334              ord = bond.GetBondType()
    335              if ord == Chem.BondType.SINGLE:
    336                nSing += 1
    337              elif ord == Chem.BondType.DOUBLE:
    338                nDoub += 1
    339              elif ord == Chem.BondType.TRIPLE:
    340                nTrip += 1
    341          else:
    342            numNeighbors-=1
    343            nHs += 1
    344        tmp = -1
    345        if atNum == 7:
    346          if numNeighbors == 1:
    347            if nHs==0 and nTrip==1 and chg==0: tmp = 23.79
    348            elif nHs==1 and nDoub==1 and chg==0: tmp = 23.85
    349            elif nHs==2 and nSing==1 and chg==0: tmp = 26.02
    350            elif nHs==2 and nDoub==1 and chg==1: tmp = 25.59
    351            elif nHs==3 and nSing==1 and chg==1: tmp = 27.64
    352          elif numNeighbors == 2:
    353            if nHs==0 and nSing==1 and nDoub==1 and chg==0: tmp = 12.36
    354            elif nHs==0 and nTrip==1 and nDoub==1 and chg==0: tmp = 13.60
    355            elif nHs==1 and nSing==2 and chg==0:
    356              if not in3Ring: tmp = 12.03
    357              else: tmp=21.94
    358            elif nHs==0 and nTrip==1 and nSing==1 and chg==1: tmp = 4.36
    359            elif nHs==1 and nDoub==1 and nSing==1 and chg==1: tmp = 13.97
    360            elif nHs==2 and nSing==2 and chg==1: tmp = 16.61
    361            elif nHs==0 and nArom==2 and chg==0: tmp = 12.89
    362            elif nHs==1 and nArom==2 and chg==0: tmp = 15.79
    363            elif nHs==1 and nArom==2 and chg==1: tmp = 14.14
    364          elif numNeighbors == 3:
    365            if nHs==0 and nSing==3 and chg==0:
    366              if not in3Ring: tmp = 3.24
    367              else: tmp = 3.01
    368            elif nHs==0 and nSing==1 and nDoub==2 and chg==0: tmp = 11.68
    369            elif nHs==0 and nSing==2 and nDoub==1 and chg==1: tmp = 3.01
    370            elif nHs==1 and nSing==3 and chg==1: tmp = 4.44
    371            elif nHs==0 and nArom==3 and chg==0: tmp = 4.41
    372            elif nHs==0 and nSing==1 and nArom==2 and chg==0: tmp = 4.93
    373            elif nHs==0 and nDoub==1 and nArom==2 and chg==0: tmp = 8.39
    374            elif nHs==0 and nArom==3 and chg==1: tmp = 4.10
    375            elif nHs==0 and nSing==1 and nArom==2 and chg==1: tmp = 3.88
    376          elif numNeighbors == 4:
    377            if nHs==0 and nSing==4 and chg==1: tmp = 0.00
    378          if tmp < 0.0:
    379            tmp = 30.5 - numNeighbors * 8.2 + nHs * 1.5
    380            if tmp < 0.0: tmp = 0.0
    381        elif atNum==8:
    382          #print(nHs,nSing,chg)
    383          if numNeighbors == 1:
    384            if nHs==0 and nDoub==1 and chg==0: tmp = 17.07
    385            elif nHs==1 and nSing==1 and chg==0: tmp = 20.23
    386            elif nHs==0 and nSing==1 and chg==-1: tmp = 23.06
    387          elif numNeighbors == 2:
    388            if nHs==0 and nSing==2 and chg==0:
    389              if not in3Ring: tmp = 9.23
    390              else: tmp = 12.53
    391            elif nHs==0 and nArom==2 and chg==0: tmp = 13.14
    392
    393          if tmp < 0.0:
    394            tmp = 28.5 - numNeighbors * 8.6 + nHs * 1.5
    395            if tmp < 0.0: tmp = 0.0
    396        if verbose:
    397          print('\t',atom.GetIdx(),atom.GetSymbol(),atNum,nHs,nSing,nDoub,nTrip,nArom,chg,tmp)
    398
    399        res[atom.GetIdx()] = tmp
    400    return res
    401
    402 -def _pyTPSA(mol,verbose=False):
    403    """ DEPRECATED: this has been reimplmented in C++
    404     calculates the polar surface area of a molecule based upon fragments
    405
    406     Algorithm in:
    407      P. Ertl, B. Rohde, P. Selzer
    408       Fast Calculation of Molecular Polar Surface Area as a Sum of Fragment-based
    409       Contributions and Its Application to the Prediction of Drug Transport
    410       Properties, J.Med.Chem. 43, 3714-3717, 2000
    411
    412     Implementation based on the Daylight contrib program tpsa.c
    413    """
    414    contribs = _pyTPSAContribs(mol,verbose=verbose)
    415    res = 0.0
    416    for contrib in contribs:
    417      res += contrib
    418    return res
    419  _pyTPSA.version="1.0.1"
    420
    421  TPSA=lambda *x,**y:rdMolDescriptors.CalcTPSA(*x,**y)
    422  TPSA.version=rdMolDescriptors._CalcTPSA_version
    423
    424
    425  if __name__ == '__main__':
    426    smis = ['C','CC','CCC','CCCC','CO','CCO','COC']
    427    smis = ['C(=O)O','c1ccccc1']
    428    for smi in smis:
    429      m = Chem.MolFromSmiles(smi)
    430      #print(smi, LabuteASA(m))
    431      print('-----------\n',smi)
    432      #print('M:',['% 4.2f'%x for x in SMR_VSA_(m)])
    433      #print('L:',['% 4.2f'%x for x in SlogP_VSA_(m)])
    434      print('P:',['% 4.2f'%x for x in PEOE_VSA_(m)])
    435      print('P:',['% 4.2f'%x for x in PEOE_VSA_(m)])
    436      print()
    437