class TestTrypsinLigandParameterization:
"""Test the parameterization of the 1D ligand"""
messy_input = get_test_data(
"1D_allH.mae", "testsystems/trypsin1d"
) # typical hand generated input for an epik calculation
messy_epik_output = get_test_data(
"1D_epik.mae", "testsystems/trypsin1d"
) # some messy epik generated output with scrambled and duplicated hydrogen names
preprocessed_mol2 = get_test_data(
"1D_preprocessed.mol2", "testsystems/trypsin1d"
) # A cleaned up mol2 file. Parameterization should work for this one
ffxml_file = get_test_data(
"1D.ffxml", "testsystems/trypsin1d"
) # A cleaned up mol2 file. Parameterization should work for this one
def test_mapping_states(self):
"""Test the generation of a clean mol2 file from an epik result."""
unique_filename = "{}.mol2".format(str(uuid4()))
protons_app.ligands.epik_results_to_mol2(
TestTrypsinLigandParameterization.messy_epik_output, unique_filename
)
assert path.isfile(unique_filename), "No output mol2 file was produced"
remove(unique_filename) # clean up after ourselves
@pytest.mark.skipif(
not is_schrodinger_suite_installed() or not found_gaff or not hasOpenEye,
reason="This test requires Schrodinger's suite, OpenEye, and gaff",
)
def test_running_epik(self):
"""Test if Epik is run successfully on the molecule."""
unique_id = str(uuid4())
unique_filename = "{}.mae".format(unique_id)
log_name = "{}.log".format(unique_id)
protons_app.ligands.generate_epik_states(
TestTrypsinLigandParameterization.messy_input,
unique_filename,
pH=7.8,
max_penalty=10.0,
workdir=None,
tautomerize=False,
)
assert path.isfile(unique_filename), "No Epik output file was produced"
epik_data = retrieve_epik_info(unique_filename)
assert len(epik_data) > 0, "No Epik data was extracted."
remove(unique_filename) # clean up after ourselves
remove(log_name)
def setup_viologen_implicit():
"""
Set up viologen in implicit solvent
"""
viologen = SystemSetup()
viologen.temperature = 300.0 * unit.kelvin
viologen.pressure = 1.0 * unit.atmospheres
viologen.timestep = 1.0 * unit.femtoseconds
viologen.collision_rate = 1.0 / unit.picoseconds
viologen.pH = 7.0
testsystems = get_test_data("viologen", "testsystems")
viologen.ffxml_files = os.path.join(testsystems,
"viologen-protons.ffxml")
viologen.gaff = os.path.join(testsystems, "gaff.xml")
viologen.forcefield = ForceField(viologen.gaff, "gaff-obc2.xml",
viologen.ffxml_files)
viologen.pdbfile = app.PDBFile(
os.path.join(testsystems, "viologen-vacuum.pdb"))
viologen.topology = viologen.pdbfile.topology
viologen.positions = viologen.pdbfile.getPositions(asNumpy=True)
viologen.constraint_tolerance = 1.0e-7
viologen.integrator = openmm.LangevinIntegrator(
viologen.temperature, viologen.collision_rate, viologen.timestep)
viologen.integrator.setConstraintTolerance(
viologen.constraint_tolerance)
viologen.system = viologen.forcefield.createSystem(
viologen.topology,
nonbondedMethod=app.NoCutoff,
constraints=app.HBonds)
viologen.cooh1 = { # indices in topology of the first cooh group
"HO": 56,
"OH": 0,
"CO": 1,
"OC": 2,
"R": 3,
}
viologen.cooh2 = { # indices in topology of the second cooh group
"HO": 57,
"OH": 27,
"CO": 25,
"OC": 26,
"R": 24,
}
viologen.simulation = app.Simulation(
viologen.topology,
viologen.system,
viologen.integrator,
TestCarboxylicAcid.platform,
)
viologen.simulation.context.setPositions(viologen.positions)
viologen.context = viologen.simulation.context
viologen.perturbations_per_trial = 10
viologen.propagations_per_step = 1
return viologen
def test_create_calibration_system(self):
"""Create a solvated imidazole system."""
# An protonated imidazole molecule in vacuum
vacuum_file = get_test_data("imidazole.pdb", "testsystems/imidazole_explicit")
input_xml = get_test_data(
"protons-imidazole-ph-feature.xml", "testsystems/imidazole_explicit"
)
output_basename = str(uuid4())
hxml = "{}-h.xml".format(str(uuid4()))
protons_app.ligands.create_hydrogen_definitions(input_xml, hxml)
protons_app.ligands.prepare_calibration_systems(
vacuum_file,
output_basename,
ffxml=input_xml,
hxml=hxml,
delete_old_H=True,
minimize=False,
)
def setup_viologen_implicit():
"""
Set up viologen in implicit solvent
"""
viologen = SystemSetup()
viologen.temperature = 300.0 * unit.kelvin
viologen.pressure = 1.0 * unit.atmospheres
viologen.timestep = 1.0 * unit.femtoseconds
viologen.collision_rate = 1.0 / unit.picoseconds
viologen.pH = 7.0
testsystems = get_test_data("viologen", "testsystems")
viologen.ffxml_files = os.path.join(testsystems, "viologen-protons.ffxml")
viologen.gaff = os.path.join(testsystems, "gaff.xml")
viologen.forcefield = ForceField(
viologen.gaff, "gaff-obc2.xml", viologen.ffxml_files
)
viologen.pdbfile = app.PDBFile(os.path.join(testsystems, "viologen-vacuum.pdb"))
viologen.topology = viologen.pdbfile.topology
viologen.positions = viologen.pdbfile.getPositions(asNumpy=True)
viologen.constraint_tolerance = 1.0e-7
viologen.integrator = openmm.LangevinIntegrator(
viologen.temperature, viologen.collision_rate, viologen.timestep
)
viologen.integrator.setConstraintTolerance(viologen.constraint_tolerance)
viologen.system = viologen.forcefield.createSystem(
viologen.topology, nonbondedMethod=app.NoCutoff, constraints=app.HBonds
)
viologen.cooh1 = { # indices in topology of the first cooh group
"HO": 56,
"OH": 0,
"CO": 1,
"OC": 2,
"R": 3,
}
viologen.cooh2 = { # indices in topology of the second cooh group
"HO": 57,
"OH": 27,
"CO": 25,
"OC": 26,
"R": 24,
}
viologen.simulation = app.Simulation(
viologen.topology,
viologen.system,
viologen.integrator,
TestCarboxylicAcid.platform,
)
viologen.simulation.context.setPositions(viologen.positions)
viologen.context = viologen.simulation.context
viologen.perturbations_per_trial = 10
viologen.propagations_per_step = 1
return viologen
def setup_amino_acid_water(three_letter_code):
"""
Set up glutamic acid in water
"""
if three_letter_code not in ["glh", "ash"]:
raise ValueError("Amino acid not available.")
aa = SystemSetup()
aa.temperature = 300.0 * unit.kelvin
aa.pressure = 1.0 * unit.atmospheres
aa.timestep = 1.0 * unit.femtoseconds
aa.collision_rate = 1.0 / unit.picoseconds
aa.pH = 7.0
testsystems = get_test_data("amino_acid", "testsystems")
aa.ffxml_files = "amber10-constph.xml"
aa.forcefield = ForceField(aa.ffxml_files, "tip3p.xml")
aa.pdbfile = app.PDBFile(
os.path.join(testsystems, "{}.pdb".format(three_letter_code))
)
aa.topology = aa.pdbfile.topology
aa.positions = aa.pdbfile.getPositions(asNumpy=True)
aa.constraint_tolerance = 1.0e-7
aa.integrator = create_compound_gbaoab_integrator(aa)
aa.integrator.setConstraintTolerance(aa.constraint_tolerance)
aa.system = aa.forcefield.createSystem(
aa.topology,
nonbondedMethod=app.PME,
nonbondedCutoff=1.0 * unit.nanometers,
constraints=app.HBonds,
rigidWater=True,
ewaldErrorTolerance=0.0005,
)
aa.system.addForce(openmm.MonteCarloBarostat(aa.pressure, aa.temperature, 25))
aa.simulation = app.Simulation(
aa.topology, aa.system, aa.integrator, TestCarboxylicAcid.platform
)
aa.simulation.context.setPositions(aa.positions)
aa.context = aa.simulation.context
aa.perturbations_per_trial = 1000
aa.propagations_per_step = 1
return aa
def setup_amino_acid_water(three_letter_code):
"""
Set up glutamic acid in water
"""
if three_letter_code not in ["glh", "ash"]:
raise ValueError("Amino acid not available.")
aa = SystemSetup()
aa.temperature = 300.0 * unit.kelvin
aa.pressure = 1.0 * unit.atmospheres
aa.timestep = 1.0 * unit.femtoseconds
aa.collision_rate = 1.0 / unit.picoseconds
aa.pH = 7.0
testsystems = get_test_data("amino_acid", "testsystems")
aa.ffxml_files = "amber10-constph.xml"
aa.forcefield = ForceField(aa.ffxml_files, "tip3p.xml")
aa.pdbfile = app.PDBFile(
os.path.join(testsystems, "{}.pdb".format(three_letter_code)))
aa.topology = aa.pdbfile.topology
aa.positions = aa.pdbfile.getPositions(asNumpy=True)
aa.constraint_tolerance = 1.0e-7
aa.integrator = create_compound_gbaoab_integrator(aa)
aa.integrator.setConstraintTolerance(aa.constraint_tolerance)
aa.system = aa.forcefield.createSystem(
aa.topology,
nonbondedMethod=app.PME,
nonbondedCutoff=1.0 * unit.nanometers,
constraints=app.HBonds,
rigidWater=True,
ewaldErrorTolerance=0.0005,
)
aa.system.addForce(
openmm.MonteCarloBarostat(aa.pressure, aa.temperature, 25))
aa.simulation = app.Simulation(aa.topology, aa.system, aa.integrator,
TestCarboxylicAcid.platform)
aa.simulation.context.setPositions(aa.positions)
aa.context = aa.simulation.context
aa.perturbations_per_trial = 1000
aa.propagations_per_step = 1
return aa
def setup_viologen_water():
"""
Set up viologen in water
"""
viologen = SystemSetup()
viologen.temperature = 300.0 * unit.kelvin
viologen.pressure = 1.0 * unit.atmospheres
viologen.timestep = 1.0 * unit.femtoseconds
viologen.collision_rate = 1.0 / unit.picoseconds
viologen.pH = 7.0
testsystems = get_test_data("viologen", "testsystems")
viologen.ffxml_files = os.path.join(testsystems,
"viologen-protons-cooh.ffxml")
viologen.gaff = os.path.join(testsystems, "gaff.xml")
viologen.forcefield = ForceField(viologen.gaff, viologen.ffxml_files,
"tip3p.xml")
viologen.pdbfile = app.PDBFile(
os.path.join(testsystems, "viologen-solvated.pdb"))
viologen.topology = viologen.pdbfile.topology
viologen.positions = viologen.pdbfile.getPositions(asNumpy=True)
viologen.constraint_tolerance = 1.0e-7
viologen.integrator = create_compound_gbaoab_integrator(viologen)
viologen.integrator.setConstraintTolerance(
viologen.constraint_tolerance)
viologen.system = viologen.forcefield.createSystem(
viologen.topology,
nonbondedMethod=app.PME,
nonbondedCutoff=1.0 * unit.nanometers,
constraints=app.HBonds,
rigidWater=True,
ewaldErrorTolerance=0.0005,
)
viologen.system.addForce(
openmm.MonteCarloBarostat(viologen.pressure, viologen.temperature,
25))
viologen.cooh1 = { # indices in topology of the first cooh group
"HO": 56,
"OH": 1,
"CO": 0,
"OC": 2,
"R": 3,
}
viologen.cooh2 = { # indices in topology of the second cooh group
"HO": 57,
"OH": 27,
"CO": 25,
"OC": 26,
"R": 24,
}
viologen.simulation = app.Simulation(
viologen.topology,
viologen.system,
viologen.integrator,
TestCarboxylicAcid.platform,
)
viologen.simulation.context.setPositions(viologen.positions)
viologen.context = viologen.simulation.context
viologen.perturbations_per_trial = 1000
viologen.propagations_per_step = 1
return viologen
def setup_viologen_water():
"""
Set up viologen in water
"""
viologen = SystemSetup()
viologen.temperature = 300.0 * unit.kelvin
viologen.pressure = 1.0 * unit.atmospheres
viologen.timestep = 1.0 * unit.femtoseconds
viologen.collision_rate = 1.0 / unit.picoseconds
viologen.pH = 7.0
testsystems = get_test_data("viologen", "testsystems")
viologen.ffxml_files = os.path.join(testsystems, "viologen-protons-cooh.ffxml")
viologen.gaff = os.path.join(testsystems, "gaff.xml")
viologen.forcefield = ForceField(
viologen.gaff, viologen.ffxml_files, "tip3p.xml"
)
viologen.pdbfile = app.PDBFile(
os.path.join(testsystems, "viologen-solvated.pdb")
)
viologen.topology = viologen.pdbfile.topology
viologen.positions = viologen.pdbfile.getPositions(asNumpy=True)
viologen.constraint_tolerance = 1.0e-7
viologen.integrator = create_compound_gbaoab_integrator(viologen)
viologen.integrator.setConstraintTolerance(viologen.constraint_tolerance)
viologen.system = viologen.forcefield.createSystem(
viologen.topology,
nonbondedMethod=app.PME,
nonbondedCutoff=1.0 * unit.nanometers,
constraints=app.HBonds,
rigidWater=True,
ewaldErrorTolerance=0.0005,
)
viologen.system.addForce(
openmm.MonteCarloBarostat(viologen.pressure, viologen.temperature, 25)
)
viologen.cooh1 = { # indices in topology of the first cooh group
"HO": 56,
"OH": 1,
"CO": 0,
"OC": 2,
"R": 3,
}
viologen.cooh2 = { # indices in topology of the second cooh group
"HO": 57,
"OH": 27,
"CO": 25,
"OC": 26,
"R": 24,
}
viologen.simulation = app.Simulation(
viologen.topology,
viologen.system,
viologen.integrator,
TestCarboxylicAcid.platform,
)
viologen.simulation.context.setPositions(viologen.positions)
viologen.context = viologen.simulation.context
viologen.perturbations_per_trial = 1000
viologen.propagations_per_step = 1
return viologen
