Package rdkit :: Package Chem :: Package MolKey :: Module MolKey

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# Source Code for Module rdkit.Chem.MolKey.MolKey

      1  #
      2  #  Copyright (c) 2015, Novartis Institutes for BioMedical Research Inc.
      3  #  All rights reserved.
      4  #
      5  # Redistribution and use in source and binary forms, with or without
      6  # modification, are permitted provided that the following conditions are
      7  # met:
      8  #
      9  #     * Redistributions of source code must retain the above copyright
     10  #       notice, this list of conditions and the following disclaimer.
     11  #     * Redistributions in binary form must reproduce the above
     12  #       copyright notice, this list of conditions and the following
     13  #       disclaimer in the documentation and/or other materials provided
     14  #       with the distribution.
     15  #     * Neither the name of Novartis Institutes for BioMedical Research Inc.
     16  #       nor the names of its contributors may be used to endorse or promote
     17  #       products derived from this software without specific prior written permission.
     18  #
     19  # THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS
     20  # "AS IS" AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT
     21  # LIMITED TO, THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR
     22  # A PARTICULAR PURPOSE ARE DISCLAIMED. IN NO EVENT SHALL THE COPYRIGHT
     23  # OWNER OR CONTRIBUTORS BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL,
     24  # SPECIAL, EXEMPLARY, OR CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT
     25  # LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES; LOSS OF USE,
     26  # DATA, OR PROFITS; OR BUSINESS INTERRUPTION) HOWEVER CAUSED AND ON ANY
     27  # THEORY OF LIABILITY, WHETHER IN CONTRACT, STRICT LIABILITY, OR TORT
     28  # (INCLUDING NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE
     29  # OF THIS SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.
     30  #
     31  # Created by Greg Landrum based on code from Thomas Mueller
     32  # August 2012
     33  #
     34  #pylint: disable=C0111,W0311
     35  try:
     36      from rdkit.Avalon import pyAvalonTools
     37  except ImportError:
     38      raise ImportError("This code requires the RDKit to be built with AvalonTools support")
     39
     40  from rdkit.Chem.MolKey import InchiInfo
     41  from rdkit import RDConfig
     42  from rdkit import Chem
     43  from collections import namedtuple
     44  import logging
     45  import os,re,uuid,base64,hashlib,tempfile
     46
     47 -class MolIdentifierException(Exception):
     48      pass
     49
     50 -class BadMoleculeException(Exception):
     51      pass
     52
     53  MOL_KEY_VERSION = '1'
     54
     55  ERROR_DICT = dict(BAD_MOLECULE=1,
     56                    ALIAS_CONVERSION_FAILED=2,
     57                    TRANSFORMED=4,
     58                    FRAGMENTS_FOUND=8,
     59                    EITHER_WARNING=16,
     60                    STEREO_ERROR=32,
     61                    DUBIOUS_STEREO_REMOVED=64,
     62                    ATOM_CLASH=128,
     63                    ATOM_CHECK_FAILED=256,
     64                    SIZE_CHECK_FAILED=512,
     65                    RECHARGED=1024,
     66                    STEREO_FORCED_BAD=2048,
     67                    STEREO_TRANSFORMED=4096,
     68                    TEMPLATE_TRANSFORMED=8192,
     69                    INCHI_COMPUTATION_ERROR=65536,
     70                    RDKIT_CONVERSION_ERROR=131072,
     71                    INCHI_READWRITE_ERROR=262144,
     72                    NULL_MOL=524288)
     73
     74  INCHI_COMPUTATION_ERROR = ERROR_DICT['INCHI_COMPUTATION_ERROR']
     75  RDKIT_CONVERSION_ERROR = ERROR_DICT['RDKIT_CONVERSION_ERROR']
     76  INCHI_READWRITE_ERROR = ERROR_DICT['INCHI_READWRITE_ERROR']
     77  NULL_MOL = ERROR_DICT['NULL_MOL']
     78
     79  BAD_SET = pyAvalonTools.StruChkResult.bad_set | INCHI_COMPUTATION_ERROR | RDKIT_CONVERSION_ERROR | INCHI_READWRITE_ERROR | NULL_MOL
     80
     81  GET_STEREO_RE = re.compile(r'^InChI=1S(.*?)/(t.*?)/m\d/s1(.*$)')
     82  NULL_SMILES_RE = re.compile(r'^\s*$|^\s*NO_STRUCTURE\s*$', re.IGNORECASE)
     83  PATTERN_NULL_MOL = r'^([\s0]+[1-9]+[\s]+V[\w]*)'
     84
     85  CHIRAL_POS = 12
     86
     87  T_NULL_MOL = (NULL_MOL, '')     # the NULL mol result tuple
     88
     89  stereo_code_dict = {}
     90  stereo_code_dict['DEFAULT'] = 0
     91  stereo_code_dict['S_ACHIR'] = 1
     92  stereo_code_dict['S_ABS'] = 2
     93  stereo_code_dict['S_REL'] = 3
     94  stereo_code_dict['S_PART'] = 4
     95  stereo_code_dict['S_UNKN'] = 5
     96  stereo_code_dict['S_ABS_ACHIR'] = 6
     97  stereo_code_dict['R_ONE'] = 11
     98  stereo_code_dict['R_REL'] = 12
     99  stereo_code_dict['R_OTHER'] = 13
    100  stereo_code_dict['MX_ENANT'] = 21
    101  stereo_code_dict['MX_DIAST'] = 22
    102  stereo_code_dict['MX_SP2'] = 31
    103  stereo_code_dict['MX_DIAST_ABS'] = 32
    104  stereo_code_dict['MX_DIAST_REL'] = 33
    105  stereo_code_dict['OTHER'] = 100
    106  stereo_code_dict['UNDEFINED'] = 200
    107
    108
    109
    110 -def _fix_all(pat, sbt, my_string) :
    111      try :
    112          new_string = re.sub(pat, sbt, my_string)
    113          return new_string
    114      except :
    115          return None
    116
    117 -def _fix_line_ends(my_string) :
    118      pat = '\r\n{0,1}'
    119      sbt = '\n'
    120      return _fix_all(pat, sbt, my_string)
    121
    122 -def _fix_chemdraw_header(my_string) :
    123      pat = '0V2000'
    124      sbt = 'V2000'
    125      return _fix_all(pat, sbt, my_string)
    126
    127 -def _ctab_has_atoms(ctab_lines):
    128      ''' look at atom count position (line 4, characters 0:3)
    129      Return True if the count is >0, False if 0.
    130      Throw BadMoleculeException if there are no characters
    131      at the required position or if they cannot be converted
    132      to a positive integer
    133      '''
    134      try:
    135          str_a_count = ctab_lines[3][0:3]
    136          a_count = int(str_a_count)
    137          if a_count < 0:
    138              raise BadMoleculeException('Atom count negative')
    139          if a_count > 0:
    140              rval = True
    141          else:
    142              rval = False
    143      except IndexError:
    144          raise BadMoleculeException('Invalid molfile format')
    145      except ValueError:
    146          raise BadMoleculeException('Expected integer')
    147
    148      return rval
    149
    150 -def _ctab_remove_chiral_flag(ctab_lines):
    151      ''' read the chiral flag (line 4, characters 12:15)
    152      and set it to 0. Return True if it was 1, False if 0.
    153      Throw BadMoleculeException if there are no characters
    154      at the required position or if they where not 0 or 1
    155      '''
    156      try:
    157          str_a_count = ctab_lines[3][12:15]
    158          a_count = int(str_a_count)
    159          if a_count == 0:
    160              rval = False
    161          elif a_count == 1:
    162              rval = True
    163              orig_line = ctab_lines[3]
    164              ctab_lines[3] = orig_line[:CHIRAL_POS] + '  0' + orig_line[CHIRAL_POS + 3:]
    165          else:
    166              raise BadMoleculeException('Expected chiral flag 0 or 1')
    167      except IndexError:
    168          raise BadMoleculeException('Invalid molfile format')
    169      except ValueError:
    170          raise BadMoleculeException('Expected integer, got {0}'.format(str_a_count))
    171
    172      return rval
    173
    174  __initCalled=False
    175 -def initStruchk(configDir=None,logFile=None):
    176    global __initCalled
    177    if configDir is None:
    178      configDir=os.path.join(RDConfig.RDDataDir,'struchk')
    179    if configDir[-1]!=os.path.sep:
    180      configDir+=os.path.sep
    181    if logFile is None:
    182      fd = tempfile.NamedTemporaryFile(suffix='.log',delete=False)
    183      fd.close()
    184      logFile= fd.name
    185    struchk_init = '''-tm
    186  -ta {0}checkfgs.trn
    187  -tm
    188  -or
    189  -ca {0}checkfgs.chk
    190  -cc
    191  -cl 3
    192  -cs
    193  -cn 999
    194  -l {1}\n'''.format(configDir, logFile)
    195    initRes=pyAvalonTools.InitializeCheckMol(struchk_init)
    196    if initRes:
    197      raise ValueError('bad result from InitializeCheckMol: '+str(initRes))
    198    __initCalled=True
    199
    200 -def CheckCTAB(ctab, isSmiles=True):
    201      if not __initCalled:
    202          initStruchk()
    203      mol_str = ctab
    204      if not mol_str:
    205          raise BadMoleculeException('Unexpected blank or NULL molecule')
    206      else:
    207          mol_str = _fix_line_ends(mol_str)
    208          mol_str = _fix_chemdraw_header(mol_str)
    209
    210          if isSmiles:                  # branch for NULL_MOL checks
    211              if mol_str and NULL_SMILES_RE.match(mol_str):
    212                  rval = T_NULL_MOL
    213              else:
    214                  rval = pyAvalonTools.CheckMoleculeString(mol_str, isSmiles)
    215          else:
    216              # decompose the ctab into lines
    217              # the line terminator may be \n or \r\n, or even r'\n'
    218              ctab_lines = mol_str.split('\n')
    219              if len(ctab_lines) <= 3:
    220                  raise BadMoleculeException('Not enough lines in CTAB')
    221              _ctab_remove_chiral_flag(ctab_lines)
    222              if not _ctab_has_atoms(ctab_lines):
    223                  rval = T_NULL_MOL
    224              else: # reassemble the ctab lines into one string.
    225                  mol_str = '\n'.join(ctab_lines)
    226                  rval = pyAvalonTools.CheckMoleculeString(mol_str, isSmiles)
    227      return rval
    228
    229  InchiResult = namedtuple('InchiResult',['error','inchi','fixed_ctab'])
    230 -def GetInchiForCTAB(ctab):
    231      """
    232      >>> from rdkit.Chem.MolKey import MolKey
    233      >>> from rdkit.Avalon import pyAvalonTools
    234      >>> res = MolKey.GetInchiForCTAB(pyAvalonTools.Generate2DCoords('c1cn[nH]c1C(Cl)Br',True))
    235      >>> res.inchi
    236      'InChI=1/C4H4BrClN2/c5-4(6)3-1-2-7-8-3/h1-2,4H,(H,7,8)/t4?/f/h8H'
    237      >>> res = MolKey.GetInchiForCTAB(pyAvalonTools.Generate2DCoords('c1c[nH]nc1C(Cl)Br',True))
    238      >>> res.inchi
    239      'InChI=1/C4H4BrClN2/c5-4(6)3-1-2-7-8-3/h1-2,4H,(H,7,8)/t4?/f/h7H'
    240      >>>
    241      """
    242      inchi = None
    243      ctab_str = ctab
    244      (strucheck_err, fixed_mol) = CheckCTAB(ctab_str, False)
    245      if strucheck_err & BAD_SET:
    246          return (strucheck_err, None, fixed_mol)
    247
    248      conversion_err = 0
    249      try:
    250          r_mol = Chem.MolFromMolBlock(fixed_mol, sanitize=False)
    251          if r_mol:
    252              inchi = Chem.MolToInchi(r_mol, '/FixedH /SUU')
    253              if not inchi:
    254                  conversion_err = INCHI_COMPUTATION_ERROR
    255          else:
    256              conversion_err = RDKIT_CONVERSION_ERROR
    257      except Chem.InchiReadWriteError:
    258          conversion_err = INCHI_READWRITE_ERROR
    259      # keep warnings from strucheck
    260      return InchiResult(strucheck_err | conversion_err, inchi, fixed_mol)
    261
    262 -def _make_racemate_inchi(inchi):
    263      """ Normalize the stereo information (t-layer) to one selected isomer. """
    264      # set stereo type = 3 (racemate) for consistency
    265      # reset inverted flag to m0 - not inverted
    266      new_stereo = '/m0/s3/'
    267      stereo_match = GET_STEREO_RE.match(inchi)
    268      if stereo_match:
    269          inchi = stereo_match.group(1) + new_stereo + stereo_match.group(2)
    270      return inchi
    271
    272 -def _get_identification_string(err, ctab, inchi, stereo_category=None, extra_stereo=None):
    273      if err & NULL_MOL :
    274          return _get_null_mol_identification_string(extra_stereo)
    275      elif err & BAD_SET:       # bad molecules get special key
    276          return _get_bad_mol_identification_string(ctab, stereo_category, extra_stereo)
    277
    278      # make key string
    279      pieces = []
    280      if inchi:
    281          pieces.append(inchi)
    282      if not stereo_category:
    283          raise MolIdentifierException('Stereo category may not be left undefined')
    284      else:
    285          pieces.append('ST=' + stereo_category)
    286      if extra_stereo:
    287          pieces.append('XTR=' + extra_stereo)
    288      key_string = '/'.join(pieces)
    289      return key_string
    290
    291 -def _get_null_mol_identification_string(extra_stereo) :
    292      key_string = str(uuid.uuid1 ())
    293      return key_string
    294
    295 -def _get_bad_mol_identification_string(ctab, stereo_category, extra_stereo):
    296      pieces = []
    297      ctab_str = ctab
    298      if ctab_str:       # make the ctab part of the key if available
    299          ctab_str = _fix_line_ends(ctab_str)
    300          ctab_str = _fix_chemdraw_header(ctab_str)
    301          ctab_str = '\n'.join(ctab_str.split('\n')[3:])
    302          pieces.append(ctab_str.replace('\n', r'\n')) # make a handy one-line string
    303      else:
    304          pass
    305      if stereo_category: # add xtra info if available
    306          key_string = 'ST={0}'.format(stereo_category)
    307          pieces.append(key_string)
    308      if extra_stereo: # add xtra info if available
    309          key_string = 'XTR={0}'.format(extra_stereo)
    310          pieces.append(key_string)
    311      key_string = '/'.join(pieces)
    312      return key_string
    313
    314 -def _identify(err, ctab, inchi, stereo_category, extra_structure_desc=None):
    315      """ Compute the molecule key based on the inchi string,
    316      stereo category as well as extra structure
    317      information """
    318      key_string = _get_identification_string(err, ctab, inchi, stereo_category, extra_structure_desc)
    319      if key_string:
    320          return "{0}|{1}".format(MOL_KEY_VERSION,
    321                                  base64.b64encode(hashlib.md5(key_string.encode('UTF-8')).digest()).decode()) #pylint: disable=E1101
    322      else:
    323          return None
    324
    325 -def _get_chiral_identification_string(n_def, n_udf) :
    326      assert n_def >= 0
    327      assert n_udf >= 0
    328      id_str = 'OTHER'
    329
    330      if n_def == 0 :             # no defined stereocenters
    331          if n_udf == 0 :         # no undefined ones either
    332              id_str = 'S_ACHIR'  # -> achiral
    333          elif n_udf == 1 :       # one undefined, no defined
    334              id_str = 'R_ONE'    # -> racemate by convention
    335          else:                   # several undefined, no defined
    336              id_str = 'S_UNKN'   # -> can't say anything based on the drawing
    337      else:                       # some stereo defined
    338          if n_udf == 0 :         # fully specified stereo
    339              id_str = 'S_ABS'    # -> absolute stereo
    340          else:                   # multiple possibilities
    341              id_str = 'S_PART'   # -> assume single compound (can usually be separated)
    342      return id_str
    343
    344 -def ErrorBitsToText(err):
    345      " returns a list of error bit descriptions for the error code provided "
    346      error_text_list = []
    347      for err_dict_key in ERROR_DICT:
    348          if (err & ERROR_DICT[err_dict_key]) > 0:
    349              error_text_list.append(err_dict_key)
    350      return error_text_list
    351
    352  MolKeyResult=namedtuple('MolKeyResult',['mol_key','error','inchi','fixed_ctab','stereo_code','stereo_comment'])
    353 -def GetKeyForCTAB(ctab,stereo_info=None,stereo_comment=None,logger=None):
    354      """
    355      >>> from rdkit.Chem.MolKey import MolKey
    356      >>> from rdkit.Avalon import pyAvalonTools
    357      >>> res=MolKey.GetKeyForCTAB(pyAvalonTools.Generate2DCoords('c1ccccc1C(F)Cl',True))
    358      >>> res.mol_key
    359      '1|L7676nfGsSIU33wkx//NCg=='
    360      >>> res.stereo_code
    361      'R_ONE'
    362      >>> res=MolKey.GetKeyForCTAB(pyAvalonTools.Generate2DCoords('c1ccccc1[C@H](F)Cl',True))
    363      >>> res.mol_key
    364      '1|Aj38EIxf13RuPDQG2A0UMw=='
    365      >>> res.stereo_code
    366      'S_ABS'
    367      >>> res=MolKey.GetKeyForCTAB(pyAvalonTools.Generate2DCoords('c1ccccc1[C@@H](F)Cl',True))
    368      >>> res.mol_key
    369      '1|9ypfMrhxn1w0ncRooN5HXw=='
    370      >>> res.stereo_code
    371      'S_ABS'
    372      >>> res=MolKey.GetKeyForCTAB(pyAvalonTools.Generate2DCoords('c1cccc(C(Br)Cl)c1[C@@H](F)Cl',True))
    373      >>> res.mol_key
    374      '1|c96jMSlbn7O9GW5d5uB9Mw=='
    375      >>> res.stereo_code
    376      'S_PART'
    377      >>> res=MolKey.GetKeyForCTAB(pyAvalonTools.Generate2DCoords('c1cccc([C@H](Br)Cl)c1[C@@H](F)Cl',True))
    378      >>> res.mol_key
    379      '1|+B+GCEardrJteE8xzYdGLA=='
    380      >>> res.stereo_code
    381      'S_ABS'
    382      >>> res=MolKey.GetKeyForCTAB(pyAvalonTools.Generate2DCoords('c1cccc(C(Br)Cl)c1C(F)Cl',True))
    383      >>> res.mol_key
    384      '1|5H9R3LvclagMXHp3Clrc/g=='
    385      >>> res.stereo_code
    386      'S_UNKN'
    387      >>> res=MolKey.GetKeyForCTAB(pyAvalonTools.Generate2DCoords('c1cccc(C(Br)Cl)c1C(F)Cl',True),stereo_info='S_REL')
    388      >>> res.mol_key
    389      '1|cqKWVsUEY6QNpGCbDaDTYA=='
    390      >>> res.stereo_code
    391      'S_REL'
    392      >>> res.inchi
    393      'InChI=1/C8H6BrCl2F/c9-7(10)5-3-1-2-4-6(5)8(11)12/h1-4,7-8H/t7?,8?'
    394
    395      """
    396      if logger is None:
    397          logger = logging
    398      try:
    399          err, inchi, fixed_mol = GetInchiForCTAB(ctab)
    400      except BadMoleculeException:
    401          logger.warn('Corrupt molecule substituting no-struct: --->\n{0}\n<----'.format(ctab))
    402          err = NULL_MOL
    403          key = _identify(err, '', '', None, None)
    404          return MolKeyResult(key, err, '', '', None, None)
    405
    406      # read or estimate stereo category and/or extra structure description
    407      stereo_category = None
    408      extra_structure_desc = stereo_comment
    409      if stereo_info:     # check stereo_info field for coded stereo category and extra stereo info
    410          info_flds = stereo_info.split(' ', 1)
    411          code_fld = info_flds[0]
    412          if code_fld in stereo_code_dict:
    413              stereo_category = code_fld
    414              if (not stereo_comment) and len(info_flds) > 1:
    415                  extra_structure_desc = info_flds[1].strip()
    416          else:
    417              logger.warn('stereo code {0} not recognized. Using default value for ctab.'.format(code_fld))
    418
    419      if not (err & BAD_SET):
    420          (n_stereo, n_undef_stereo, is_meso, dummy) = InchiInfo.InchiInfo(inchi).get_sp3_stereo()['main']['non-isotopic']
    421          if stereo_category == None or stereo_category == 'DEFAULT' :  # compute if not set
    422              stereo_category = _get_chiral_identification_string(n_stereo - n_undef_stereo,
    423                                                                 n_undef_stereo)
    424      else:
    425          raise NotImplementedError("currently cannot generate correct keys for molecules with struchk errors")
    426      key = _identify(err, fixed_mol, inchi, stereo_category, extra_structure_desc)
    427      return MolKeyResult(key, err, inchi, fixed_mol, stereo_category, extra_structure_desc)
    428
    429
    430
    431  #------------------------------------
    432  #
    433  #  doctest boilerplate
    434  #
    435 -def _test():
    436    import doctest,sys
    437    return doctest.testmod(sys.modules["__main__"])
    438
    439
    440  if __name__ == '__main__':
    441    import sys
    442    failed,tried = _test()
    443    sys.exit(failed)
    444