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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, unittest, os, sys

from rdkit import RDConfig
from rdkit.RDLogger import logger
logger = logger()
from rdkit import Chem
from rdkit.Chem import rdSubstructLibrary
import time
import pickle
import tempfile

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 fpholderCls in [None, rdSubstructLibrary.PatternHolder]:
      for holder in [rdSubstructLibrary.MolHolder(), rdSubstructLibrary.CachedMolHolder(),
                     rdSubstructLibrary.CachedSmilesMolHolder()]:
        if fpholderCls: fpholder = fpholderCls()
        else: fpholder = None
        slib_ = rdSubstructLibrary.SubstructLibrary(holder, fpholder)
        for i in range(100):
            m = Chem.MolFromSmiles("c1ccccc1")
            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)
          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 fpholderCls in [None, rdSubstructLibrary.PatternHolder]:
      for holder in [rdSubstructLibrary.MolHolder(), rdSubstructLibrary.CachedMolHolder(),
                     rdSubstructLibrary.CachedSmilesMolHolder()]:
        if fpholderCls: fpholder = fpholderCls()
        else: fpholder = None
        
        slib_ = rdSubstructLibrary.SubstructLibrary(holder, fpholder)
        mols = []
        for i in range(100):
            m = Chem.MolFromSmiles("c1ccccc1")
            self.assertEqual(slib_.AddMol(m), i*2)
            mols.append(m)
            m2 = Chem.MolFromSmiles("CCCC")
            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))))

          res = slib.GetMatches(m2)
          self.assertEqual(len(res), 100)
          self.assertTrue(set(res) == set(list(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")

  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 StringIO, BytesIO
    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"
    ]
    
    mols = [Chem.MolFromSmiles(smi) for smi in pdb_ligands]
    holder = rdSubstructLibrary.CachedMolHolder()
    patterns = rdSubstructLibrary.PatternHolder()
    
    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)

      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)) )

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