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""" This is a rough coverage test of the python wrapper for the SubstructLibrary

it is intended to be shallow but broad.
"""

import doctest
import logging
import os
import sys
import unittest

from rdkit import RDConfig, RDLogger, rdBase
from rdkit.RDLogger import logger

logger = logger()
import pickle
import tempfile
import time

from rdkit import Chem
from rdkit.Chem import rdSubstructLibrary, rdGeneralizedSubstruct, rdTautomerQuery


def load_tests(loader, tests, ignore):
  tests.addTests(doctest.DocTestSuite(rdSubstructLibrary))
  return tests


def makeStereoExamples():
  el = "NO"
  mols = []
  for e in el:
    for e2 in el:
      if e != e2:
        smi = "C1CCO[C@@](%s)(%s)1" % (e, e2)
        m = Chem.MolFromSmiles(smi)
        if m:
          mols.append(m)
        smi = "C1CCO[C@](%s)(%s)1" % (e, e2)
        m = Chem.MolFromSmiles(smi)
        if m:
          mols.append(m)

  return mols


class TestCase(unittest.TestCase):

  def setUp(self):
    pass

  def test0SubstructLibrary(self):
    for keyholderCls in [None, rdSubstructLibrary.KeyFromPropHolder]:
      for fpholderCls in [None, rdSubstructLibrary.PatternHolder]:
        for holder in [
            rdSubstructLibrary.MolHolder(),
            rdSubstructLibrary.CachedMolHolder(),
            rdSubstructLibrary.CachedSmilesMolHolder()
        ]:
          if fpholderCls:
            fpholder = fpholderCls()
          else:
            fpholder = None
          if keyholderCls:
            keyholder = keyholderCls()
            self.assertEqual(keyholder.GetPropName(), "_Name")
          else:
            keyholder = None
          slib_ = rdSubstructLibrary.SubstructLibrary(holder, fpholder, keyholder)
          for i in range(100):
            m = Chem.MolFromSmiles("c1ccccc1")
            m.SetProp("_Name", str(i))
            self.assertEqual(slib_.AddMol(m), i)

          libs = [slib_]
          if rdSubstructLibrary.SubstructLibraryCanSerialize():
            serialized1 = pickle.loads(pickle.dumps(slib_))
            serialized2 = rdSubstructLibrary.SubstructLibrary(slib_.Serialize())
            libs.append(serialized1)
            libs.append(serialized2)

          for slib in libs:
            res = slib.GetMatches(m)

            if keyholderCls:
              for idx in res:
                self.assertEqual(str(idx), slib.GetKeyHolder().GetKey(idx))
              self.assertEqual([str(idx) for idx in res], list(slib.GetKeyHolder().GetKeys(res)))

            t2 = time.time()
            self.assertTrue(len(res) == 100)

            res = slib.GetMatches(m)

            self.assertEqual(len(res), 100)
            self.assertTrue(set(res) == set(list(range(100))))

            res = slib.GetMatches(m, maxResults=100)
            self.assertEqual(len(res), 100)
            self.assertEqual(len(slib.GetMatches(m, startIdx=0, endIdx=100)), 100)

            self.assertTrue(slib.HasMatch(m))
            self.assertEqual(slib.CountMatches(m), 100)

  def test1SubstructLibrary(self):
    for keyholderCls in [None, rdSubstructLibrary.KeyFromPropHolder]:
      for fpholderCls in [None, rdSubstructLibrary.PatternHolder]:
        for holder in [
            rdSubstructLibrary.MolHolder(),
            rdSubstructLibrary.CachedMolHolder(),
            rdSubstructLibrary.CachedSmilesMolHolder()
        ]:
          if fpholderCls:
            fpholder = fpholderCls()
          else:
            fpholder = None
          if keyholderCls:
            keyholder = keyholderCls()
            self.assertEqual(keyholder.GetPropName(), "_Name")
          else:
            keyholder = None

          slib_ = rdSubstructLibrary.SubstructLibrary(holder, fpholder, keyholder)
          mols = []
          for i in range(100):
            m = Chem.MolFromSmiles("c1ccccc1")
            m.SetProp("_Name", str(i * 2))
            self.assertEqual(slib_.AddMol(m), i * 2)
            mols.append(m)
            m2 = Chem.MolFromSmiles("CCCC")
            m2.SetProp("_Name", str(i * 2 + 1))
            self.assertEqual(slib_.AddMol(m2), i * 2 + 1)
            mols.append(m2)

          libs = [slib_]
          if rdSubstructLibrary.SubstructLibraryCanSerialize():
            serialized1 = pickle.loads(pickle.dumps(slib_))
            serialized2 = rdSubstructLibrary.SubstructLibrary(slib_.Serialize())
            libs.append(serialized1)
            libs.append(serialized2)

          for slib in libs:
            res = slib.GetMatches(m)
            self.assertEqual(len(res), 100)
            self.assertEqual(set(res), set(list(range(0, 200, 2))))
            if keyholderCls:
              self.assertEqual([str(idx) for idx in res], [str(idx) for idx in range(0, 200, 2)])

            res = slib.GetMatches(m2)
            self.assertEqual(len(res), 100)
            self.assertTrue(set(res) == set(list(range(1, 200, 2))))
            if keyholderCls:
              self.assertEqual([str(idx) for idx in res], [str(idx) for idx in range(1, 200, 2)])

            res = slib.GetMatches(m)
            self.assertEqual(len(res), 100)

            res = slib.GetMatches(m, maxResults=100)
            self.assertEqual(len(res), 100)

            self.assertEqual(len(slib.GetMatches(m, startIdx=0, endIdx=50 * 2)), 50)
            self.assertEqual(len(slib.GetMatches(m2, startIdx=1, endIdx=50 * 2 + 1)), 50)

            self.assertTrue(slib.HasMatch(m))
            self.assertTrue(slib.HasMatch(m2))
            self.assertEqual(slib.CountMatches(m), 100)
            self.assertEqual(slib.CountMatches(m2), 100)

  def testOptions(self):
    mols = makeStereoExamples() * 10

    for holderCls in [
        rdSubstructLibrary.MolHolder,
        rdSubstructLibrary.CachedMolHolder,
        rdSubstructLibrary.CachedSmilesMolHolder,
        rdSubstructLibrary.CachedTrustedSmilesMolHolder,
    ]:
      holder = holderCls()
      slib_ = rdSubstructLibrary.SubstructLibrary(holder, None)

      for mol in mols:
        slib_.AddMol(mol)

      libs = [slib_]
      if rdSubstructLibrary.SubstructLibraryCanSerialize():
        serialized1 = pickle.loads(pickle.dumps(slib_))
        serialized2 = rdSubstructLibrary.SubstructLibrary(slib_.Serialize())
        libs.append(serialized1)
        libs.append(serialized2)

      for slib in libs:
        core = Chem.MolFromSmarts("C-1-C-C-O-C(-*)(-*)1")
        res = slib.GetMatches(core)
        self.assertEqual(len(res),
                         len([x for x in mols if x.HasSubstructMatch(core, useChirality=True)]))

        core = Chem.MolFromSmarts("C-1-C-C-O-C(-[O])(-[N])1")
        core.SetProp("core", "core")
        res = slib.GetMatches(core, useChirality=False)
        self.assertEqual(len(res),
                         len([x for x in mols if x.HasSubstructMatch(core, useChirality=False)]))

        core = Chem.MolFromSmarts("C-1-C-C-O-[C@@](-[O])(-[N])1")
        res = slib.GetMatches(core, useChirality=False)
        self.assertEqual(len(res),
                         len([x for x in mols if x.HasSubstructMatch(core, useChirality=False)]))

        core = Chem.MolFromSmarts("C-1-C-C-O-[C@@](-[O])(-[N])1")
        res = slib.GetMatches(core)
        self.assertEqual(len(res),
                         len([x for x in mols if x.HasSubstructMatch(core, useChirality=True)]))

  def testSmilesCache(self):
    mols = makeStereoExamples() * 10
    holder = rdSubstructLibrary.CachedSmilesMolHolder()

    slib_ = rdSubstructLibrary.SubstructLibrary(holder, None)

    for mol in mols:
      holder.AddSmiles(Chem.MolToSmiles(mol, isomericSmiles=True))

    libs = [slib_]
    if rdSubstructLibrary.SubstructLibraryCanSerialize():
      serialized1 = pickle.loads(pickle.dumps(slib_))
      serialized2 = rdSubstructLibrary.SubstructLibrary(slib_.Serialize())
      libs.append(serialized1)
      libs.append(serialized2)

    for slib in libs:
      core = Chem.MolFromSmarts("C-1-C-C-O-C(-*)(-*)1")
      res = slib.GetMatches(core)
      self.assertEqual(len(res),
                       len([x for x in mols if x.HasSubstructMatch(core, useChirality=True)]))

      core = Chem.MolFromSmarts("C-1-C-C-O-C(-[O])(-[N])1")
      core.SetProp("core", "core")
      res = slib.GetMatches(core, useChirality=False)
      self.assertEqual(len(res),
                       len([x for x in mols if x.HasSubstructMatch(core, useChirality=False)]))

      core = Chem.MolFromSmarts("C-1-C-C-O-[C@@](-[O])(-[N])1")
      res = slib.GetMatches(core, useChirality=False)
      self.assertEqual(len(res),
                       len([x for x in mols if x.HasSubstructMatch(core, useChirality=False)]))

      core = Chem.MolFromSmarts("C-1-C-C-O-[C@@](-[O])(-[N])1")
      res = slib.GetMatches(core)
      self.assertEqual(len(res),
                       len([x for x in mols if x.HasSubstructMatch(core, useChirality=True)]))

  def testTrustedSmilesCache(self):
    mols = makeStereoExamples() * 10
    holder = rdSubstructLibrary.CachedTrustedSmilesMolHolder()

    slib_ = rdSubstructLibrary.SubstructLibrary(holder, None)

    for mol in mols:
      holder.AddSmiles(Chem.MolToSmiles(mol, isomericSmiles=True))

    libs = [slib_]
    if rdSubstructLibrary.SubstructLibraryCanSerialize():
      serialized1 = pickle.loads(pickle.dumps(slib_))
      serialized2 = rdSubstructLibrary.SubstructLibrary(slib_.Serialize())
      libs.append(serialized1)
      libs.append(serialized2)

    for slib in libs:
      core = Chem.MolFromSmarts("C-1-C-C-O-C(-*)(-*)1")
      res = slib.GetMatches(core)
      self.assertEqual(len(res),
                       len([x for x in mols if x.HasSubstructMatch(core, useChirality=True)]))

      core = Chem.MolFromSmarts("C-1-C-C-O-C(-[O])(-[N])1")
      core.SetProp("core", "core")
      res = slib.GetMatches(core, useChirality=False)
      self.assertEqual(len(res),
                       len([x for x in mols if x.HasSubstructMatch(core, useChirality=False)]))

      core = Chem.MolFromSmarts("C-1-C-C-O-[C@@](-[O])(-[N])1")
      res = slib.GetMatches(core, useChirality=False)
      self.assertEqual(len(res),
                       len([x for x in mols if x.HasSubstructMatch(core, useChirality=False)]))

      core = Chem.MolFromSmarts("C-1-C-C-O-[C@@](-[O])(-[N])1")
      res = slib.GetMatches(core)
      self.assertEqual(len(res),
                       len([x for x in mols if x.HasSubstructMatch(core, useChirality=True)]))

  def testBinaryCache(self):
    mols = makeStereoExamples() * 10
    holder = rdSubstructLibrary.CachedMolHolder()

    slib_ = rdSubstructLibrary.SubstructLibrary(holder, None)

    for mol in mols:
      holder.AddBinary(mol.ToBinary())

    libs = [slib_]
    if rdSubstructLibrary.SubstructLibraryCanSerialize():
      serialized1 = pickle.loads(pickle.dumps(slib_))
      serialized2 = rdSubstructLibrary.SubstructLibrary(slib_.Serialize())
      libs.append(serialized1)
      libs.append(serialized2)

    for slib in libs:
      core = Chem.MolFromSmarts("C-1-C-C-O-C(-*)(-*)1")
      res = slib.GetMatches(core)
      self.assertEqual(len(res),
                       len([x for x in mols if x.HasSubstructMatch(core, useChirality=True)]))

      core = Chem.MolFromSmarts("C-1-C-C-O-C(-[O])(-[N])1")
      core.SetProp("core", "core")
      res = slib.GetMatches(core, useChirality=False)
      self.assertEqual(len(res),
                       len([x for x in mols if x.HasSubstructMatch(core, useChirality=False)]))

      core = Chem.MolFromSmarts("C-1-C-C-O-[C@@](-[O])(-[N])1")
      res = slib.GetMatches(core, useChirality=False)
      self.assertEqual(len(res),
                       len([x for x in mols if x.HasSubstructMatch(core, useChirality=False)]))

      core = Chem.MolFromSmarts("C-1-C-C-O-[C@@](-[O])(-[N])1")
      res = slib.GetMatches(core)
      self.assertEqual(len(res),
                       len([x for x in mols if x.HasSubstructMatch(core, useChirality=True)]))

  def testRingSmartsWithTrustedSmiles(self):
    pat = Chem.MolFromSmarts("[C&R1]")
    pat2 = Chem.MolFromSmarts("C@C")  # ring bond
    holder = rdSubstructLibrary.CachedTrustedSmilesMolHolder()
    lib = rdSubstructLibrary.SubstructLibrary(holder)
    lib.AddMol(Chem.MolFromSmiles("C1CC1"))

    # make sure we can get an unsanitized molecule that fails (no ring info)
    print("Testing atom rings")
    with self.assertRaises(RuntimeError):
      holder.GetMol(0).HasSubstructMatch(pat)
    print("testing bond rings")
    with self.assertRaises(RuntimeError):
      holder.GetMol(0).HasSubstructMatch(pat2)

    # shouldn't throw
    print("searching atom rings")
    self.assertEqual(len(lib.GetMatches(pat)), 1)
    self.assertEqual(lib.CountMatches(pat), 1)
    print("searching bond rings")
    self.assertEqual(len(lib.GetMatches(pat2)), 1)
    self.assertEqual(lib.CountMatches(pat2), 1)
    print("done")

  @unittest.skipIf(not rdBase._serializationEnabled, "not built with serialization support")
  def test_init_from_and_to_stream(self):
    mols = makeStereoExamples() * 10
    holder = rdSubstructLibrary.CachedSmilesMolHolder()

    # one day I'll fix this, but we need to write text but read binary
    #  grrr....  something about the python_streambuf handler.
    slib = rdSubstructLibrary.SubstructLibrary(holder, None)

    for mol in mols:
      holder.AddSmiles(Chem.MolToSmiles(mol, isomericSmiles=True))

    if rdSubstructLibrary.SubstructLibraryCanSerialize():
      fd, path = tempfile.mkstemp()
      with open(path, 'w') as file:
        slib.ToStream(file)

      with open(path, 'rb') as file:
        slib2 = rdSubstructLibrary.SubstructLibrary()
        slib2.InitFromStream(file)
        self.assertEqual(len(slib), len(slib2))

    from io import BytesIO, StringIO
    s = StringIO()
    slib.ToStream(s)

    sb = BytesIO(s.getvalue().encode("ascii"))
    self.assertTrue(len(sb.getvalue()) > 0)
    slib3 = rdSubstructLibrary.SubstructLibrary()
    slib3.InitFromStream(sb)
    self.assertEqual(len(slib), len(slib2))

  def test_addpatterns(self):
    pdb_ligands = [
      "CCS(=O)(=O)c1ccc(OC)c(Nc2ncc(-c3cccc(-c4ccccn4)c3)o2)c1",
      "COc1ccc(S(=O)(=O)NCC2CC2)cc1Nc1ncc(-c2cccc(-c3cccnc3)c2)o1",
      "COc1ccc(-c2oc3ncnc(N)c3c2-c2ccc(NC(=O)Nc3cc(C(F)(F)F)ccc3F)cc2)cc1",
      "COC(=O)Nc1nc2ccc(Oc3ccc(NC(=O)Nc4cc(C(F)(F)F)ccc4F)cc3)cc2[nH]1",
      "COc1cc(Nc2ncnc(-c3cccnc3Nc3ccccc3)n2)cc(OC)c1OC",
      "O=C(Nc1ccc(Oc2ccccc2)cc1)c1cccnc1NCc1ccncc1", "O=C(Nc1ccc(Oc2ccccc2)cc1)c1cccnc1NCc1ccncc1",
      "CNC(=O)c1cc(Oc2ccc3[nH]c(Nc4ccc(Cl)c(C(F)(F)F)c4)nc3c2)ccn1",
      "CNC(=O)c1cc(Oc2ccc3oc(Nc4ccc(Cl)c(OCC5CCC[NH+]5C)c4)nc3c2)ccn1",
      "CNC(=O)c1cc(Oc2ccc3oc(Nc4ccc(Cl)c(OCC5CCC[NH+]5C)c4)nc3c2)ccn1",
      "COc1cc2nccc(Oc3ccc4c(c3)OCCN4C(=O)Nc3ccc(Cl)cc3)c2cc1OC",
      "CNC(=O)c1c(C)oc2cc(Oc3cc[nH+]c4cc(OCCN5CCOCC5)ccc34)ccc12",
      "COc1cc2[nH+]ccc(Oc3ccc4c(C(=O)Nc5ccc(Cl)cc5)cccc4c3)c2cc1OC",
      "COc1cc2[nH+]ccc(Oc3ccc4c(C(=O)Nc5ccc(Cl)cc5)cccc4c3)c2cc1OC",
      "COc1cc2[nH+]ccc(Oc3ccc4c(C(=O)NC5CC5)cccc4c3)c2cc1OC",
      "COc1cc2[nH+]ccc(Oc3ccc4c(C(=O)NC5CC5)cccc4c3)c2cc1OC",
      "Cc1ccc(C(=O)Nc2cc(CCC[NH+](C)C)cc(C(F)(F)F)c2)cc1Nc1ncccc1-c1ccncn1",
      "COc1cc(Nc2nccc(Nc3ccc4c(C)n[nH]c4c3)n2)cc(OC)c1OC",
      "COc1cc(Nc2nccc(N(C)c3ccc4c(C)n[nH]c4c3)n2)cc(OC)c1OC",
      "Cc1ccn(-c2ccc3c(c2)NCC3(C)C)c(=O)c1-c1ccc2nc(N)ncc2c1",
      "Cc1ccn(-c2ccc3c(c2)NCC3(C)C)c(=O)c1-c1ccc2nc(N)ncc2c1",
      "Cc1ccc(C(=O)NCCC2CCCC2)cc1C(=O)Nc1ccc(N)nc1", "Cc1ccc(C(=O)NCCC2CCCC2)cc1C(=O)Nc1ccc(N)nc1",
      "Cc1ccn(-c2cccc(C(F)(F)F)c2)c(=O)c1-c1ccc2nc(N)ncc2c1",
      "Cc1ccn(-c2cccc(C(F)(F)F)c2)c(=O)c1-c1ccc2nc(N)ncc2c1",
      "O=C(Nc1cncnc1)c1c(Cl)ccc2c(Nc3cccc(C(F)(F)F)c3)noc12",
      "O=C(Nc1cncnc1)c1c(Cl)ccc2c(Nc3cccc(C(F)(F)F)c3)noc12",
      "CC1(C)CNc2cc(NC(=O)c3cccnc3NCc3ccncc3)ccc21", "CC1(C)CNc2cc(NC(=O)c3cccnc3NCc3ccncc3)ccc21"
    ]

    for patterns in [
        rdSubstructLibrary.PatternHolder(),
        rdSubstructLibrary.TautomerPatternHolder()
    ]:
      mols = [Chem.MolFromSmiles(smi) for smi in pdb_ligands]
      holder = rdSubstructLibrary.CachedMolHolder()
      slib_with_patterns = rdSubstructLibrary.SubstructLibrary(holder, patterns)

      for mol in mols:
        slib_with_patterns.AddMol(mol)

      for nthreads in [1, 2, 0]:
        slib_without_patterns = rdSubstructLibrary.SubstructLibrary(holder, None)
        rdSubstructLibrary.AddPatterns(slib_without_patterns, nthreads)
        # check for seg fault
        #  were the fingerprints really created
        slib_without_patterns.GetFpHolder().GetFingerprint(0)
        for mol in mols:
          l1 = slib_with_patterns.CountMatches(mol)
          l2 = slib_without_patterns.CountMatches(mol)
          self.assertTrue(l1)
          self.assertEqual(l1, l2)

  def test_basic_addpatterns(self):
    # add mols
    pdb_ligands = [
      "CCS(=O)(=O)c1ccc(OC)c(Nc2ncc(-c3cccc(-c4ccccn4)c3)o2)c1",
      "COc1ccc(S(=O)(=O)NCC2CC2)cc1Nc1ncc(-c2cccc(-c3cccnc3)c2)o1",
      "COc1ccc(-c2oc3ncnc(N)c3c2-c2ccc(NC(=O)Nc3cc(C(F)(F)F)ccc3F)cc2)cc1",
      "COC(=O)Nc1nc2ccc(Oc3ccc(NC(=O)Nc4cc(C(F)(F)F)ccc4F)cc3)cc2[nH]1",
      "COc1cc(Nc2ncnc(-c3cccnc3Nc3ccccc3)n2)cc(OC)c1OC",
      "O=C(Nc1ccc(Oc2ccccc2)cc1)c1cccnc1NCc1ccncc1", "O=C(Nc1ccc(Oc2ccccc2)cc1)c1cccnc1NCc1ccncc1",
      "CNC(=O)c1cc(Oc2ccc3[nH]c(Nc4ccc(Cl)c(C(F)(F)F)c4)nc3c2)ccn1",
      "CNC(=O)c1cc(Oc2ccc3oc(Nc4ccc(Cl)c(OCC5CCC[NH+]5C)c4)nc3c2)ccn1",
      "CNC(=O)c1cc(Oc2ccc3oc(Nc4ccc(Cl)c(OCC5CCC[NH+]5C)c4)nc3c2)ccn1",
      "COc1cc2nccc(Oc3ccc4c(c3)OCCN4C(=O)Nc3ccc(Cl)cc3)c2cc1OC",
      "CNC(=O)c1c(C)oc2cc(Oc3cc[nH+]c4cc(OCCN5CCOCC5)ccc34)ccc12",
      "COc1cc2[nH+]ccc(Oc3ccc4c(C(=O)Nc5ccc(Cl)cc5)cccc4c3)c2cc1OC",
      "COc1cc2[nH+]ccc(Oc3ccc4c(C(=O)Nc5ccc(Cl)cc5)cccc4c3)c2cc1OC",
      "COc1cc2[nH+]ccc(Oc3ccc4c(C(=O)NC5CC5)cccc4c3)c2cc1OC",
      "COc1cc2[nH+]ccc(Oc3ccc4c(C(=O)NC5CC5)cccc4c3)c2cc1OC",
      "Cc1ccc(C(=O)Nc2cc(CCC[NH+](C)C)cc(C(F)(F)F)c2)cc1Nc1ncccc1-c1ccncn1",
      "COc1cc(Nc2nccc(Nc3ccc4c(C)n[nH]c4c3)n2)cc(OC)c1OC",
      "COc1cc(Nc2nccc(N(C)c3ccc4c(C)n[nH]c4c3)n2)cc(OC)c1OC",
      "Cc1ccn(-c2ccc3c(c2)NCC3(C)C)c(=O)c1-c1ccc2nc(N)ncc2c1",
      "Cc1ccn(-c2ccc3c(c2)NCC3(C)C)c(=O)c1-c1ccc2nc(N)ncc2c1",
      "Cc1ccc(C(=O)NCCC2CCCC2)cc1C(=O)Nc1ccc(N)nc1", "Cc1ccc(C(=O)NCCC2CCCC2)cc1C(=O)Nc1ccc(N)nc1",
      "Cc1ccn(-c2cccc(C(F)(F)F)c2)c(=O)c1-c1ccc2nc(N)ncc2c1",
      "Cc1ccn(-c2cccc(C(F)(F)F)c2)c(=O)c1-c1ccc2nc(N)ncc2c1",
      "O=C(Nc1cncnc1)c1c(Cl)ccc2c(Nc3cccc(C(F)(F)F)c3)noc12",
      "O=C(Nc1cncnc1)c1c(Cl)ccc2c(Nc3cccc(C(F)(F)F)c3)noc12",
      "CC1(C)CNc2cc(NC(=O)c3cccnc3NCc3ccncc3)ccc21", "CC1(C)CNc2cc(NC(=O)c3cccnc3NCc3ccncc3)ccc21"
    ]

    for holder in [
        rdSubstructLibrary.CachedSmilesMolHolder(),
        rdSubstructLibrary.CachedTrustedSmilesMolHolder()
    ]:
      for smi in pdb_ligands:
        holder.AddSmiles(smi)

      for patttern in [
          None,
          rdSubstructLibrary.PatternHolder(),
          rdSubstructLibrary.TautomerPatternHolder()
      ]:
        lib = rdSubstructLibrary.SubstructLibrary(holder)
        rdSubstructLibrary.AddPatterns(lib, numThreads=-1)
        self.assertEqual(len(lib.GetMolHolder()), len(lib.GetFpHolder()))
        for smi in pdb_ligands:
          self.assertTrue(lib.CountMatches(Chem.MolFromSmiles(smi)))

  def test_PatternHolder(self):
    for holder in [rdSubstructLibrary.PatternHolder, rdSubstructLibrary.TautomerPatternHolder]:
      fname = os.path.join(os.environ["RDBASE"], "Data", "NCI", "first_5K.smi")
      suppl = Chem.SmilesMolSupplier(fname, delimiter="\t", titleLine=False)
      mols1 = rdSubstructLibrary.CachedTrustedSmilesMolHolder()
      fps1 = holder(2048)
      ssslib1 = rdSubstructLibrary.SubstructLibrary(mols1, fps1)
      mols2 = rdSubstructLibrary.CachedTrustedSmilesMolHolder()
      fps2 = holder()
      ssslib2 = rdSubstructLibrary.SubstructLibrary(mols2, fps2)

      RDLogger.DisableLog('rdApp.error')
      for i in range(0, 1000, 10):
        try:
          mol = suppl[i]
        except Exception:
          continue
        if (not mol):
          continue
        mols1.AddSmiles(Chem.MolToSmiles(mol))
        fps1.AddFingerprint(fps1.MakeFingerprint(mol))
        ssslib2.AddMol(mol)
      RDLogger.EnableLog('rdApp.error')
      query = Chem.MolFromSmarts("N")
      self.assertIsNotNone(query)
      matches1 = sorted(ssslib1.GetMatches(query))
      matches2 = sorted(ssslib2.GetMatches(query))
      self.assertEqual(len(matches1), len(matches2))
      self.assertTrue(all([m1 == matches2[i] for i, m1 in enumerate(matches1)]))

  def testMolBundles(self):
    ssl = rdSubstructLibrary.SubstructLibrary()
    for smi in ('CCOC', 'CCNC', 'COOCOO', 'CCNC', 'CCCC'):
      ssl.AddMol(Chem.MolFromSmiles(smi))
    bndl = Chem.MolBundle()
    for smi in ('COC', 'CCC'):
      bndl.AddMol(Chem.MolFromSmiles(smi))
    self.assertEqual(list(ssl.GetMatches(bndl)), [0, 4])
    bndl.AddMol(Chem.MolFromSmiles('CN'))
    self.assertEqual(list(sorted(ssl.GetMatches(bndl))), [0, 1, 3, 4])

  def testSubstructParameters(self):
    ssl = rdSubstructLibrary.SubstructLibrary()
    for smi in ('C[C@H](F)Cl', 'C[C@@H](F)Cl', 'CC(F)Cl'):
      ssl.AddMol(Chem.MolFromSmiles(smi))
    bndl = Chem.MolBundle()
    for smi in ('C[C@H](F)Cl', ):
      bndl.AddMol(Chem.MolFromSmiles(smi))
    params = Chem.SubstructMatchParameters()
    self.assertEqual(list(sorted(ssl.GetMatches(bndl, params))), [0, 1, 2])

    params.useChirality = True
    self.assertEqual(list(sorted(ssl.GetMatches(bndl, params))), [0])

  def testSearchOrder(self):
    for keyholder in [None, rdSubstructLibrary.KeyFromPropHolder()]:
      ssl = rdSubstructLibrary.SubstructLibrary(rdSubstructLibrary.MolHolder(), keyholder)
      for idx, smi in enumerate(("CCCOC", "CCCCOCC", "CCOC", "COC", "CCCCCOC")):
        m = Chem.MolFromSmiles(smi)
        m.SetProp("_Name", str(idx))
        ssl.AddMol(m)

      ssl.SetSearchOrder((3, 2, 0, 1, 4))
      self.assertEqual(ssl.GetSearchOrder(), (3, 2, 0, 1, 4))
      qm = Chem.MolFromSmiles('COC')
      self.assertEqual(list(ssl.GetMatches(qm, maxResults=2)), [3, 2])
      self.assertEqual(list(ssl.GetMatches(qm, maxResults=2)), [3, 2])
      if keyholder:
        self.assertEqual(keyholder.GetPropName(), "_Name")
        self.assertEqual(list(ssl.GetKeyHolder().GetKeys(ssl.GetMatches(qm, maxResults=2))),
                         ['3', '2'])

      # make sure we can clear the search order:
      ssl.SetSearchOrder(None)
      self.assertEqual(ssl.GetSearchOrder(), ())

      ssl.SetSearchOrder((3, 2, 0, 1, 4))
      self.assertEqual(ssl.GetSearchOrder(), (3, 2, 0, 1, 4))

      ssl.SetSearchOrder([])
      self.assertEqual(ssl.GetSearchOrder(), ())

  def testSearchOrder2(self):
    ssl = rdSubstructLibrary.SubstructLibrary()
    for smi in ("CCCOC", "CCCCOCC", "CCOC", "COC", "CCCCCOC"):
      ssl.AddMol(Chem.MolFromSmiles(smi))

    def setSearchSmallestFirst(sslib):
      searchOrder = list(range(len(sslib)))
      holder = sslib.GetMolHolder()
      searchOrder.sort(key=lambda x, holder=holder: holder.GetMol(x).GetNumAtoms())
      sslib.SetSearchOrder(searchOrder)

    setSearchSmallestFirst(ssl)
    qm = Chem.MolFromSmiles('COC')
    self.assertEqual(list(ssl.GetMatches(qm)), [3, 2, 0, 1, 4])

  def testPropHolder(self):
    for propname in [None, 'foo']:
      if propname is None:
        keyholder = rdSubstructLibrary.KeyFromPropHolder()
      else:
        keyholder = rdSubstructLibrary.KeyFromPropHolder(propname)

      library = rdSubstructLibrary.SubstructLibrary(rdSubstructLibrary.MolHolder(), keyholder)
      m = Chem.MolFromSmiles('CCC')
      if propname is None:
        self.assertEqual(keyholder.GetPropName(), "_Name")
      else:
        self.assertEqual(keyholder.GetPropName(), propname)

      if propname:
        m.SetProp(propname, 'Z11234')
      else:
        m.SetProp("_Name", 'Z11234')

      library.AddMol(m)
      indices = library.GetMatches(m)
      self.assertEqual(['Z11234'], list(library.GetKeyHolder().GetKeys(indices)))

  def test_bad_smiles(self):
    # add mols
    pdb_ligands = [
      "&CCS(=O)(=O)c1ccc(OC)c(Nc2ncc(-c3cccc(-c4ccccn4)c3)o2)c1",
      "&COc1ccc(S(=O)(=O)NCC2CC2)cc1Nc1ncc(-c2cccc(-c3cccnc3)c2)o1",
      "&COc1ccc(-c2oc3ncnc(N)c3c2-c2ccc(NC(=O)Nc3cc(C(F)(F)F)ccc3F)cc2)cc1",
      "&COC(=O)Nc1nc2ccc(Oc3ccc(NC(=O)Nc4cc(C(F)(F)F)ccc4F)cc3)cc2[nH]1",
      "&COc1cc(Nc2ncnc(-c3cccnc3Nc3ccccc3)n2)cc(OC)c1OC",
      "&O=C(Nc1ccc(Oc2ccccc2)cc1)c1cccnc1NCc1ccncc1",
      "&O=C(Nc1ccc(Oc2ccccc2)cc1)c1cccnc1NCc1ccncc1",
      "&CNC(=O)c1cc(Oc2ccc3[nH]c(Nc4ccc(Cl)c(C(F)(F)F)c4)nc3c2)ccn1",
      "&CNC(=O)c1cc(Oc2ccc3oc(Nc4ccc(Cl)c(OCC5CCC[NH+]5C)c4)nc3c2)ccn1",
      "&CNC(=O)c1cc(Oc2ccc3oc(Nc4ccc(Cl)c(OCC5CCC[NH+]5C)c4)nc3c2)ccn1",
      "&COc1cc2nccc(Oc3ccc4c(c3)OCCN4C(=O)Nc3ccc(Cl)cc3)c2cc1OC",
      "&CNC(=O)c1c(C)oc2cc(Oc3cc[nH+]c4cc(OCCN5CCOCC5)ccc34)ccc12",
      "&COc1cc2[nH+]ccc(Oc3ccc4c(C(=O)Nc5ccc(Cl)cc5)cccc4c3)c2cc1OC",
      "&COc1cc2[nH+]ccc(Oc3ccc4c(C(=O)Nc5ccc(Cl)cc5)cccc4c3)c2cc1OC",
      "&COc1cc2[nH+]ccc(Oc3ccc4c(C(=O)NC5CC5)cccc4c3)c2cc1OC",
      "&COc1cc2[nH+]ccc(Oc3ccc4c(C(=O)NC5CC5)cccc4c3)c2cc1OC",
      "&Cc1ccc(C(=O)Nc2cc(CCC[NH+](C)C)cc(C(F)(F)F)c2)cc1Nc1ncccc1-c1ccncn1",
      "&COc1cc(Nc2nccc(Nc3ccc4c(C)n[nH]c4c3)n2)cc(OC)c1OC",
      "&COc1cc(Nc2nccc(N(C)c3ccc4c(C)n[nH]c4c3)n2)cc(OC)c1OC",
      "&Cc1ccn(-c2ccc3c(c2)NCC3(C)C)c(=O)c1-c1ccc2nc(N)ncc2c1",
      "&Cc1ccn(-c2ccc3c(c2)NCC3(C)C)c(=O)c1-c1ccc2nc(N)ncc2c1",
      "&Cc1ccc(C(=O)NCCC2CCCC2)cc1C(=O)Nc1ccc(N)nc1",
      "&Cc1ccc(C(=O)NCCC2CCCC2)cc1C(=O)Nc1ccc(N)nc1",
      "&Cc1ccn(-c2cccc(C(F)(F)F)c2)c(=O)c1-c1ccc2nc(N)ncc2c1",
      "&Cc1ccn(-c2cccc(C(F)(F)F)c2)c(=O)c1-c1ccc2nc(N)ncc2c1",
      "&O=C(Nc1cncnc1)c1c(Cl)ccc2c(Nc3cccc(C(F)(F)F)c3)noc12",
      "&O=C(Nc1cncnc1)c1c(Cl)ccc2c(Nc3cccc(C(F)(F)F)c3)noc12",
      "&CC1(C)CNc2cc(NC(=O)c3cccnc3NCc3ccncc3)ccc21", "&CC1(C)CNc2cc(NC(=O)c3cccnc3NCc3ccncc3)ccc21"
    ]
    # this test is really verbose, so disable the actual output without
    # disabling that logging happens.
    rdBase.LogToPythonLogger()
    pylog = logging.getLogger("rdkit")
    pylog.setLevel(logging.CRITICAL)
    for holder in [
        rdSubstructLibrary.CachedSmilesMolHolder(),
        rdSubstructLibrary.CachedTrustedSmilesMolHolder()
    ]:
      for smi in pdb_ligands:
        holder.AddSmiles(smi)
      lib = rdSubstructLibrary.SubstructLibrary(holder)
      # this should excercise the logger
      smi = "CCS(=O)(=O)c1ccc(OC)c(Nc2ncc(-c3cccc(-c4ccccn4)c3)o2)c1"
      self.assertEqual(0, lib.CountMatches(Chem.MolFromSmiles(smi)))

      # test add patterns
      rdSubstructLibrary.AddPatterns(lib, -1)
    pylog.setLevel(logging.WARN)
    rdBase.LogToCppStreams()

  @unittest.skipIf(not rdBase._serializationEnabled, "not built with serialization support")
  def test_using_xqms(self):
    smis = ["COCC=O", "COOCC=O", "COOOCC=O", "COOOOCC=O"]

    for holder in [
        rdSubstructLibrary.CachedSmilesMolHolder(),
        rdSubstructLibrary.CachedTrustedSmilesMolHolder()
    ]:
      for smi in smis:
        holder.AddSmiles(smi)
      fph = rdSubstructLibrary.TautomerPatternHolder()
      lib = rdSubstructLibrary.SubstructLibrary(holder)

      mol = Chem.MolFromSmiles("COCC")
      xqm = rdGeneralizedSubstruct.CreateExtendedQueryMol(mol)
      res = lib.GetMatches(xqm)
      self.assertEqual(list(res), [0])
      self.assertTrue(lib.HasMatch(xqm))
      self.assertEqual(lib.CountMatches(xqm), 1)

      mol = Chem.MolFromSmiles("COC=CO")
      xqm = rdGeneralizedSubstruct.CreateExtendedQueryMol(mol)
      res = lib.GetMatches(xqm)
      self.assertEqual(list(res), [0])
      self.assertTrue(lib.HasMatch(xqm))
      self.assertEqual(lib.CountMatches(xqm), 1)

      mol = Chem.MolFromSmiles("COCC |LN:1:1.3|")
      xqm = rdGeneralizedSubstruct.CreateExtendedQueryMol(mol)
      res = lib.GetMatches(xqm)
      self.assertEqual(list(res), [0, 1, 2])
      self.assertTrue(lib.HasMatch(xqm))
      self.assertEqual(lib.CountMatches(xqm), 3)

      mol = Chem.MolFromSmiles("COC=CO |LN:1:1.3|")
      xqm = rdGeneralizedSubstruct.CreateExtendedQueryMol(mol)
      res = lib.GetMatches(xqm)
      self.assertEqual(list(res), [0, 1, 2])
      self.assertTrue(lib.HasMatch(xqm))
      self.assertEqual(lib.CountMatches(xqm), 3)

      mol = Chem.MolFromSmiles("CNC=CO |LN:1:1.3|")
      xqm = rdGeneralizedSubstruct.CreateExtendedQueryMol(mol)
      res = lib.GetMatches(xqm)
      self.assertEqual(list(res), [])
      self.assertFalse(lib.HasMatch(xqm))
      self.assertEqual(lib.CountMatches(xqm), 0)


if __name__ == '__main__':
  unittest.main()