from rdkit import RDConfig
import sys, os
from time import sleep
from multiprocessing import Process, Value
import unittest
from rdkit import Chem
from rdkit.Chem import ChemicalForceFields
from rdkit.Chem import rdMolTransforms


class OptSafe:

  def __init__(self):
    self.minInfLoop = """minInfLoop
     RDKit          3D

  7  5  0  0  0  0  0  0  0  0999 V2000
    1.7321   -0.5000    0.0000 Br  0  0  0  0  0  0  0  0  0  0  0  0
    0.8660   -0.0000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000   -0.5000    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.5000   -1.3660    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8660   -1.0000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5000    0.3660    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.2321   -0.5000    0.0000 Br  0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0  0  0  0
  2  3  1  0  0  0  0
  3  4  1  0  0  0  0
  3  5  1  0  0  0  0
  3  6  1  0  0  0  0
M  CHG  2   3   1   7  -1
M  END"""

  def uffOptFunc(self, v, mol):
    ff = ChemicalForceFields.UFFGetMoleculeForceField(mol)
    try:
      ff.Minimize()
    except RuntimeError:
      pass
    v.value = True
    return

  def mmffOptFunc(self, v, mol):
    mp = ChemicalForceFields.MMFFGetMoleculeProperties(mol)
    ff = ChemicalForceFields.MMFFGetMoleculeForceField(mol, mp)
    try:
      ff.Minimize()
    except RuntimeError:
      pass
    v.value = True
    return

  def opt(self, mol, optFunc):
    OPT_SLEEP_SEC = 0.2
    MAX_OPT_SLEEP_SEC = 3
    v = Value('b', False)
    optProcess = Process(target=optFunc, args=(v, mol))
    optProcess.start()
    s = 0.0
    while ((s < MAX_OPT_SLEEP_SEC) and (not v.value)):
      s += OPT_SLEEP_SEC
      sleep(OPT_SLEEP_SEC)
    if (not v.value):
      sys.stderr.write('Killing Minimize() or it will loop indefinitely\n')
      optProcess.terminate()
    optProcess.join()
    return bool(v.value)


class TestCase(unittest.TestCase):

  def setUp(self):
    self.molB = """butane
     RDKit          3D
butane
 17 16  0  0  0  0  0  0  0  0999 V2000
    0.0000    0.0000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.4280    0.0000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7913   -0.2660    0.9927 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.9040    1.3004   -0.3485 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5407    2.0271    0.3782 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.5407    1.5664   -1.3411 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.3320    1.3004   -0.3485 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6953    1.5162   -1.3532 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.8080    0.0192    0.0649 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.4447   -0.7431   -0.6243 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.4447   -0.1966    1.0697 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.8980    0.0192    0.0649 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.6954    2.0627    0.3408 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.7913   -0.7267   -0.7267 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3633    0.7267    0.7267 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3633   -0.9926    0.2660 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3633    0.2660   -0.9926 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0  0  0  0
  1 15  1  0  0  0  0
  1 16  1  0  0  0  0
  1 17  1  0  0  0  0
  2  3  1  0  0  0  0
  2  4  1  0  0  0  0
  2 14  1  0  0  0  0
  4  5  1  0  0  0  0
  4  6  1  0  0  0  0
  4  7  1  0  0  0  0
  7  8  1  0  0  0  0
  7  9  1  0  0  0  0
  7 13  1  0  0  0  0
  9 10  1  0  0  0  0
  9 11  1  0  0  0  0
  9 12  1  0  0  0  0
M  END"""

  def testUFFMinInfLoop(self):
    os = OptSafe()
    m = Chem.MolFromMolBlock(os.minInfLoop)
    self.assertTrue(m)
    ok = False
    try:
      ok = os.opt(m, os.uffOptFunc)
    except RuntimeError:
      ok = True
      pass
    self.assertTrue(ok)

  def testUFFDistanceConstraints(self):
    m = Chem.MolFromMolBlock(self.molB, True, False)
    ff = ChemicalForceFields.UFFGetMoleculeForceField(m)
    self.assertTrue(ff)
    ff.UFFAddDistanceConstraint(1, 3, False, 2.0, 2.0, 1.0e5)
    r = ff.Minimize()
    self.assertTrue(r == 0)
    conf = m.GetConformer()
    dist = rdMolTransforms.GetBondLength(conf, 1, 3)
    self.assertTrue(dist > 1.99)
    ff = ChemicalForceFields.UFFGetMoleculeForceField(m)
    self.assertTrue(ff)
    ff.UFFAddDistanceConstraint(1, 3, True, -0.2, 0.2, 1.0e5)
    r = ff.Minimize()
    self.assertTrue(r == 0)
    conf = m.GetConformer()
    dist = rdMolTransforms.GetBondLength(conf, 1, 3)
    self.assertTrue(dist > 1.79)

  def testUFFAngleConstraints(self):
    m = Chem.MolFromMolBlock(self.molB, True, False)
    ff = ChemicalForceFields.UFFGetMoleculeForceField(m)
    self.assertTrue(ff)
    ff.UFFAddAngleConstraint(1, 3, 6, False, 90.0, 90.0, 1.0e5)
    r = ff.Minimize()
    self.assertTrue(r == 0)
    conf = m.GetConformer()
    angle = rdMolTransforms.GetAngleDeg(conf, 1, 3, 6)
    self.assertTrue(int(angle) == 90)
    ff = ChemicalForceFields.UFFGetMoleculeForceField(m)
    self.assertTrue(ff)
    ff.UFFAddAngleConstraint(1, 3, 6, True, -10.0, 10.0, 1.0e5)
    r = ff.Minimize()
    self.assertTrue(r == 0)
    conf = m.GetConformer()
    angle = rdMolTransforms.GetAngleDeg(conf, 1, 3, 6)
    self.assertTrue(int(angle) == 100)
    ff = ChemicalForceFields.UFFGetMoleculeForceField(m)
    self.assertTrue(ff)
    ff.UFFAddAngleConstraint(1, 3, 6, False, -10.0, 10.0, 1.0e5)
    r = ff.Minimize()
    self.assertTrue(r == 0)
    conf = m.GetConformer()
    angle = rdMolTransforms.GetAngleDeg(conf, 1, 3, 6)
    self.assertEqual(int(angle), 10)

  def testUFFTorsionConstraints(self):
    m = Chem.MolFromMolBlock(self.molB, True, False)
    conf = m.GetConformer()
    rdMolTransforms.SetDihedralDeg(conf, 1, 3, 6, 8, 15.0)
    ff = ChemicalForceFields.UFFGetMoleculeForceField(m)
    self.assertTrue(ff)
    ff.UFFAddTorsionConstraint(1, 3, 6, 8, False, 10.0, 20.0, 1.0e5)
    r = ff.Minimize()
    self.assertTrue(r == 0)
    dihedral = rdMolTransforms.GetDihedralDeg(conf, 1, 3, 6, 8)
    self.assertTrue(int(dihedral) == 20)
    rdMolTransforms.SetDihedralDeg(conf, 1, 3, 6, 8, -30.0)
    ff = ChemicalForceFields.UFFGetMoleculeForceField(m)
    self.assertTrue(ff)
    ff.UFFAddTorsionConstraint(1, 3, 6, 8, True, -10.0, 8.0, 1.0e5)
    r = ff.Minimize()
    self.assertTrue(r == 0)
    conf = m.GetConformer()
    dihedral = rdMolTransforms.GetDihedralDeg(conf, 1, 3, 6, 8)
    self.assertEquals(int(dihedral), -40)
    rdMolTransforms.SetDihedralDeg(conf, 1, 3, 6, 8, -10.0)
    ff = ChemicalForceFields.UFFGetMoleculeForceField(m)
    self.assertTrue(ff)
    ff.UFFAddTorsionConstraint(1, 3, 6, 8, False, -10.0, 8.0, 1.0e6)
    r = ff.Minimize(500)
    self.assertTrue(r == 0)
    conf = m.GetConformer()
    dihedral = rdMolTransforms.GetDihedralDeg(conf, 1, 3, 6, 8)
    self.assertTrue(int(dihedral) == -10)

  def testUFFPositionConstraints(self):
    m = Chem.MolFromMolBlock(self.molB, True, False)
    ff = ChemicalForceFields.UFFGetMoleculeForceField(m)
    self.assertTrue(ff)
    conf = m.GetConformer()
    p = conf.GetAtomPosition(1)
    ff.UFFAddPositionConstraint(1, 0.3, 1.0e5)
    r = ff.Minimize()
    self.assertTrue(r == 0)
    q = conf.GetAtomPosition(1)
    self.assertTrue((p - q).Length() < 0.3)

  def testUFFFixedAtoms(self):
    m = Chem.MolFromMolBlock(self.molB, True, False)
    ff = ChemicalForceFields.UFFGetMoleculeForceField(m)
    self.assertTrue(ff)
    conf = m.GetConformer()
    fp = conf.GetAtomPosition(1)
    ff.AddFixedPoint(1)
    r = ff.Minimize()
    self.assertTrue(r == 0)
    fq = conf.GetAtomPosition(1)
    self.assertTrue((fp - fq).Length() < 0.01)

  def testMMFFMinInfLoop(self):
    os = OptSafe()
    m = Chem.MolFromMolBlock(os.minInfLoop)
    self.assertTrue(m)
    ok = False
    try:
      ok = os.opt(m, os.mmffOptFunc)
    except RuntimeError:
      ok = True
      pass
    self.assertTrue(ok)

  def testMMFFDistanceConstraints(self):
    m = Chem.MolFromMolBlock(self.molB, True, False)
    mp = ChemicalForceFields.MMFFGetMoleculeProperties(m)
    ff = ChemicalForceFields.MMFFGetMoleculeForceField(m, mp)
    self.assertTrue(ff)
    ff.MMFFAddDistanceConstraint(1, 3, False, 2.0, 2.0, 1.0e5)
    r = ff.Minimize()
    self.assertTrue(r == 0)
    conf = m.GetConformer()
    dist = rdMolTransforms.GetBondLength(conf, 1, 3)
    self.assertTrue(dist > 1.99)
    ff = ChemicalForceFields.MMFFGetMoleculeForceField(m, mp)
    self.assertTrue(ff)
    ff.MMFFAddDistanceConstraint(1, 3, True, -0.2, 0.2, 1.0e5)
    r = ff.Minimize()
    self.assertTrue(r == 0)
    conf = m.GetConformer()
    dist = rdMolTransforms.GetBondLength(conf, 1, 3)
    self.assertTrue(dist > 1.79)

  def testMMFFAngleConstraints(self):
    m = Chem.MolFromMolBlock(self.molB, True, False)
    mp = ChemicalForceFields.MMFFGetMoleculeProperties(m)
    ff = ChemicalForceFields.MMFFGetMoleculeForceField(m, mp)
    self.assertTrue(ff)
    ff.MMFFAddAngleConstraint(1, 3, 6, False, 90.0, 90.0, 1.0e5)
    r = ff.Minimize()
    self.assertTrue(r == 0)
    conf = m.GetConformer()
    angle = rdMolTransforms.GetAngleDeg(conf, 1, 3, 6)
    self.assertTrue(int(angle) == 90)
    ff = ChemicalForceFields.MMFFGetMoleculeForceField(m, mp)
    self.assertTrue(ff)
    ff.MMFFAddAngleConstraint(1, 3, 6, True, -10.0, 10.0, 1.0e5)
    r = ff.Minimize()
    self.assertTrue(r == 0)
    conf = m.GetConformer()
    angle = rdMolTransforms.GetAngleDeg(conf, 1, 3, 6)
    self.assertTrue(int(angle) == 100)
    ff = ChemicalForceFields.MMFFGetMoleculeForceField(m, mp)
    self.assertTrue(ff)
    ff.MMFFAddAngleConstraint(1, 3, 6, False, -10.0, 10.0, 1.0e5)
    r = ff.Minimize()
    self.assertTrue(r == 0)
    conf = m.GetConformer()
    angle = rdMolTransforms.GetAngleDeg(conf, 1, 3, 6)
    self.assertEquals(int(angle), 10)  #(int(angle) == 10)

  def testMMFFTorsionConstraints(self):
    m = Chem.MolFromMolBlock(self.molB, True, False)
    conf = m.GetConformer()
    rdMolTransforms.SetDihedralDeg(conf, 1, 3, 6, 8, 15.0)
    mp = ChemicalForceFields.MMFFGetMoleculeProperties(m)
    ff = ChemicalForceFields.MMFFGetMoleculeForceField(m, mp)
    self.assertTrue(ff)
    ff.MMFFAddTorsionConstraint(1, 3, 6, 8, False, 10.0, 20.0, 1.0e5)
    r = ff.Minimize()
    self.assertTrue(r == 0)
    dihedral = rdMolTransforms.GetDihedralDeg(conf, 1, 3, 6, 8)
    self.assertEquals(int(dihedral), 20)
    rdMolTransforms.SetDihedralDeg(conf, 1, 3, 6, 8, -30.0)
    ff = ChemicalForceFields.MMFFGetMoleculeForceField(m, mp)
    self.assertTrue(ff)
    ff.MMFFAddTorsionConstraint(1, 3, 6, 8, True, -10.0, 8.0, 1.0e5)
    r = ff.Minimize()
    self.assertTrue(r == 0)
    conf = m.GetConformer()
    dihedral = rdMolTransforms.GetDihedralDeg(conf, 1, 3, 6, 8)
    self.assertTrue(int(dihedral) == -40)
    rdMolTransforms.SetDihedralDeg(conf, 1, 3, 6, 8, -10.0)
    ff = ChemicalForceFields.MMFFGetMoleculeForceField(m, mp)
    self.assertTrue(ff)
    ff.MMFFAddTorsionConstraint(1, 3, 6, 8, False, -10.0, 8.0, 1.0e5)
    r = ff.Minimize(1000)
    self.assertTrue(r == 0)
    conf = m.GetConformer()
    dihedral = rdMolTransforms.GetDihedralDeg(conf, 1, 3, 6, 8)
    self.assertTrue(int(dihedral) == -10)

  def testMMFFPositionConstraints(self):
    m = Chem.MolFromMolBlock(self.molB, True, False)
    mp = ChemicalForceFields.MMFFGetMoleculeProperties(m)
    ff = ChemicalForceFields.MMFFGetMoleculeForceField(m, mp)
    self.assertTrue(ff)
    conf = m.GetConformer()
    p = conf.GetAtomPosition(1)
    ff.MMFFAddPositionConstraint(1, 0.3, 1.0e5)
    r = ff.Minimize()
    self.assertTrue(r == 0)
    q = conf.GetAtomPosition(1)
    self.assertTrue((p - q).Length() < 0.3)

  def testMMFFFixedAtoms(self):
    m = Chem.MolFromMolBlock(self.molB, True, False)
    mp = ChemicalForceFields.MMFFGetMoleculeProperties(m)
    ff = ChemicalForceFields.MMFFGetMoleculeForceField(m, mp)
    self.assertTrue(ff)
    conf = m.GetConformer()
    fp = conf.GetAtomPosition(1)
    ff.AddFixedPoint(1)
    r = ff.Minimize()
    self.assertTrue(r == 0)
    fq = conf.GetAtomPosition(1)
    self.assertTrue((fp - fq).Length() < 0.01)


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