def test_create_constantphcalibration_with_reporters(self):
"""Test running a calibration using constant-pH with reporters."""
pdb = app.PDBxFile(
get_test_data(
"glu_ala_his-solvated-minimized-renamed.cif", "testsystems/tripeptides"
)
)
forcefield = app.ForceField(
"amber10-constph.xml", "ions_tip3p.xml", "tip3p.xml"
)
system = forcefield.createSystem(
pdb.topology,
nonbondedMethod=app.PME,
nonbondedCutoff=1.0 * unit.nanometers,
constraints=app.HBonds,
rigidWater=True,
ewaldErrorTolerance=0.0005,
)
temperature = 300 * unit.kelvin
integrator = GBAOABIntegrator(
temperature=temperature,
collision_rate=1.0 / unit.picoseconds,
timestep=2.0 * unit.femtoseconds,
constraint_tolerance=1.0e-7,
external_work=False,
)
ncmcintegrator = GBAOABIntegrator(
temperature=temperature,
collision_rate=1.0 / unit.picoseconds,
timestep=2.0 * unit.femtoseconds,
constraint_tolerance=1.0e-7,
external_work=True,
)
compound_integrator = mm.CompoundIntegrator()
compound_integrator.addIntegrator(integrator)
compound_integrator.addIntegrator(ncmcintegrator)
pressure = 1.0 * unit.atmosphere
system.addForce(mm.MonteCarloBarostat(pressure, temperature))
driver = ForceFieldProtonDrive(
temperature,
pdb.topology,
system,
forcefield,
["amber10-constph.xml"],
pressure=pressure,
perturbations_per_trial=2,
propagations_per_step=1,
)
# prep the driver for calibration
driver.enable_calibration(SAMSApproach.ONESITE, group_index=-1)
simulation = app.ConstantPHSimulation(
pdb.topology,
system,
compound_integrator,
driver,
platform=self._default_platform,
)
simulation.context.setPositions(pdb.positions)
simulation.context.setVelocitiesToTemperature(temperature)
# Outputfile for reporters
newname = uuid4().hex + ".nc"
ncfile = netCDF4.Dataset(newname, "w")
tr = TitrationReporter(ncfile, 1)
mr = MetadataReporter(ncfile)
nr = NCMCReporter(ncfile, 1)
sr = SAMSReporter(ncfile, 1)
simulation.update_reporters.append(tr)
simulation.update_reporters.append(mr)
simulation.update_reporters.append(nr)
simulation.calibration_reporters.append(sr)
simulation.step(1)
# Update the titration states using the uniform proposal
simulation.update(1)
# Adapt the weights using binary update.
simulation.adapt()
# Attempt to prevent segfaults by closing files
ncfile.close()
def test_create_importance_sampling_reporters(self):
"""Instantiate a ConstantPHSimulation at 300K/1 atm for a small peptide using importance sampling with reporters."""
pdb = app.PDBxFile(
get_test_data(
"glu_ala_his-solvated-minimized-renamed.cif", "testsystems/tripeptides"
)
)
forcefield = app.ForceField(
"amber10-constph.xml", "ions_tip3p.xml", "tip3p.xml"
)
system = forcefield.createSystem(
pdb.topology,
nonbondedMethod=app.PME,
nonbondedCutoff=1.0 * unit.nanometers,
constraints=app.HBonds,
rigidWater=True,
ewaldErrorTolerance=0.0005,
)
temperature = 300 * unit.kelvin
integrator = GBAOABIntegrator(
temperature=temperature,
collision_rate=1.0 / unit.picoseconds,
timestep=2.0 * unit.femtoseconds,
constraint_tolerance=1.0e-7,
external_work=False,
)
ncmcintegrator = GBAOABIntegrator(
temperature=temperature,
collision_rate=1.0 / unit.picoseconds,
timestep=2.0 * unit.femtoseconds,
constraint_tolerance=1.0e-7,
external_work=True,
)
compound_integrator = mm.CompoundIntegrator()
compound_integrator.addIntegrator(integrator)
compound_integrator.addIntegrator(ncmcintegrator)
pressure = 1.0 * unit.atmosphere
system.addForce(mm.MonteCarloBarostat(pressure, temperature))
driver = ForceFieldProtonDrive(
temperature,
pdb.topology,
system,
forcefield,
["amber10-constph.xml"],
pressure=pressure,
perturbations_per_trial=0,
sampling_method=SamplingMethod.IMPORTANCE,
)
simulation = app.ConstantPHSimulation(
pdb.topology,
system,
compound_integrator,
driver,
platform=self._default_platform,
)
simulation.context.setPositions(pdb.positions)
simulation.context.setVelocitiesToTemperature(temperature)
newname = uuid4().hex + ".nc"
ncfile = netCDF4.Dataset(newname, "w")
tr = TitrationReporter(ncfile, 1)
mr = MetadataReporter(ncfile)
nr = NCMCReporter(ncfile, 1)
simulation.update_reporters.append(tr)
simulation.update_reporters.append(mr)
simulation.update_reporters.append(nr)
# Regular MD step
simulation.step(1)
# Update the titration states using the uniform proposal
niters = 3
for x in range(niters):
simulation.update(1)
n_total_states = np.product([len(group) for group in driver.titrationGroups])
assert (
len(ncfile["Protons/Titration/update"][:]) == n_total_states * niters
), "The wrong number of updates were recorded"
work_values = np.split(ncfile["Protons/NCMC/total_work"][:], niters)
init_states = ncfile["Protons/NCMC/initial_state"][:, :]
assert np.all(init_states == 0), "States should all be zero at the start."
first_run = work_values[0]
assert np.all(
np.unique(first_run) == np.sort(first_run)
), "No work values should be duplicated."
# Since instanteneous switching is used, this should be true
for x in range(1, niters):
assert np.all(
np.isclose(work_values[x], first_run)
), "Work should be equal for all states."
# Switch state
driver.set_titration_state(0, 3, updateContextParameters=True, updateIons=True)
driver.set_titration_state(1, 1, updateContextParameters=True, updateIons=True)
simulation.update(1)
assert (
ncfile["Protons/NCMC/initial_state"][-n_total_states, 0] == 3
), "Initial state was not changed correctly."
assert (
ncfile["Protons/NCMC/initial_state"][-n_total_states, 1] == 1
), "Initial state was not changed correctly."
work_values = np.split(ncfile["Protons/NCMC/total_work"][:], niters + 1)
assert not np.all(
np.isclose(work_values[0], work_values[-1])
), "Work values starting from different state should differ."
return
def test_create_constantphcalibration_resume(self):
"""Test running a calibration using constant-pH."""
pdb = app.PDBxFile(
get_test_data(
"glu_ala_his-solvated-minimized-renamed.cif", "testsystems/tripeptides"
)
)
forcefield = app.ForceField(
"amber10-constph.xml", "ions_tip3p.xml", "tip3p.xml"
)
system = forcefield.createSystem(
pdb.topology,
nonbondedMethod=app.PME,
nonbondedCutoff=1.0 * unit.nanometers,
constraints=app.HBonds,
rigidWater=True,
ewaldErrorTolerance=0.0005,
)
temperature = 300 * unit.kelvin
integrator = GBAOABIntegrator(
temperature=temperature,
collision_rate=1.0 / unit.picoseconds,
timestep=2.0 * unit.femtoseconds,
constraint_tolerance=1.0e-7,
external_work=False,
)
ncmcintegrator = GBAOABIntegrator(
temperature=temperature,
collision_rate=1.0 / unit.picoseconds,
timestep=2.0 * unit.femtoseconds,
constraint_tolerance=1.0e-7,
external_work=True,
)
compound_integrator = mm.CompoundIntegrator()
compound_integrator.addIntegrator(integrator)
compound_integrator.addIntegrator(ncmcintegrator)
pressure = 1.0 * unit.atmosphere
system.addForce(mm.MonteCarloBarostat(pressure, temperature))
driver = ForceFieldProtonDrive(
temperature,
pdb.topology,
system,
forcefield,
["amber10-constph.xml"],
pressure=pressure,
perturbations_per_trial=0,
)
driver.enable_calibration(SAMSApproach.ONESITE, group_index=-1)
simulation = app.ConstantPHSimulation(
pdb.topology,
system,
compound_integrator,
driver,
platform=self._default_platform,
)
simulation.context.setPositions(pdb.positions)
simulation.context.setVelocitiesToTemperature(temperature)
simulation.step(1)
# Update the titration states using the uniform proposal
simulation.update(1)
# Adapt the weights using binary update, a few times just to rack up the counters.
for x in range(5):
simulation.adapt()
# retrieve the samsProperties
# TODO use deserialize proton drive for this
xml = simulation.drive.state_to_xml()
driver2 = NCMCProtonDrive(
temperature,
pdb.topology,
system,
pressure=pressure,
perturbations_per_trial=0,
)
driver2.state_from_xml_tree(etree.fromstring(xml))
integrator2 = GBAOABIntegrator(
temperature=temperature,
collision_rate=1.0 / unit.picoseconds,
timestep=2.0 * unit.femtoseconds,
constraint_tolerance=1.0e-7,
external_work=False,
)
ncmcintegrator2 = GBAOABIntegrator(
temperature=temperature,
collision_rate=1.0 / unit.picoseconds,
timestep=2.0 * unit.femtoseconds,
constraint_tolerance=1.0e-7,
external_work=True,
)
compound_integrator2 = mm.CompoundIntegrator()
compound_integrator2.addIntegrator(integrator2)
compound_integrator2.addIntegrator(ncmcintegrator2)
# Make a new calibration and do another step, ignore the state for this example
simulation2 = app.ConstantPHSimulation(
pdb.topology,
system,
compound_integrator2,
driver2,
platform=self._default_platform,
)
assert (
simulation2.drive.calibration_state._stage
is simulation.drive.calibration_state._stage
)
# get going then
simulation2.context.setPositions(pdb.positions)
simulation2.context.setVelocitiesToTemperature(temperature)
simulation2.step(1)
# Update the titration states using the uniform proposal
simulation2.update(1)
# Adapt the weights using binary update.
simulation2.adapt()
assert (
simulation2.drive.calibration_state._current_adaptation
== -simulation.drive.calibration_state._min_burn + 6
), "The resumed calibration does not have the right adaptation_index"
def test_create_peptide_calibration_with_residue_pools_using_protons_xml():
"""Test if protons.xml can be used to successfully create a peptide Simulation object in OpenMM and
Instantiate a ForceFieldProtonDrive, while using pools of residues to sample from,
and calibrate histidine."""
sys_details = SystemSetup()
sys_details.timestep = 0.5 * unit.femtoseconds
sys_details.temperature = 300.0 * unit.kelvin
sys_details.collision_rate = 1.0 / unit.picosecond
sys_details.pressure = 1.0 * unit.atmospheres
sys_details.barostatInterval = 25
sys_details.constraint_tolerance = 1.0e-7
app.Topology.loadBondDefinitions(bonds_path)
# Load pdb file with protons compatible residue names
pdbx = app.PDBxFile(
get_test_data(
"glu_ala_his-solvated-minimized-renamed.cif", "testsystems/tripeptides"
)
)
forcefield = app.ForceField(ffxml_path, ions_spce_path, "spce.xml")
# System Configuration
nonbondedMethod = app.PME
constraints = app.AllBonds
rigidWater = True
sys_details.constraintTolerance = 1.0e-7
# Simulation Options
platform = mm.Platform.getPlatformByName("Reference")
# Prepare the Simulation
topology = pdbx.topology
positions = pdbx.positions
system = forcefield.createSystem(
topology,
nonbondedMethod=nonbondedMethod,
constraints=constraints,
rigidWater=rigidWater,
)
system.addForce(
mm.MonteCarloBarostat(
sys_details.pressure, sys_details.temperature, sys_details.barostatInterval
)
)
integrator = create_compound_gbaoab_integrator(testsystem=sys_details)
driver = ForceFieldProtonDrive(
sys_details.temperature,
topology,
system,
forcefield,
ffxml_path,
pressure=sys_details.pressure,
perturbations_per_trial=1,
)
pools = {"glu": [0], "his": [1], "glu-his": [0, 1]}
driver.define_pools(pools)
driver.enable_calibration(SAMSApproach.ONESITE, group_index=1)
sams_sampler = SAMSCalibrationEngine(driver) # SAMS on HIS
simulation = app.Simulation(topology, system, integrator, platform)
simulation.context.setPositions(positions)
simulation.context.setVelocitiesToTemperature(sys_details.temperature)
driver.attach_context(simulation.context)
# run one step and one update
simulation.step(1)
driver.update(UniformProposal(), nattempts=1, residue_pool="his")
sams_sampler.adapt_zetas()
# Clean up so that the classes remain unmodified
# unit test specific errors might occur otherwise when loading files due
# to class side effects
app.Topology.unloadStandardBonds()
def test_peptide_system_integrity():
"""
Set up peptide, and assure that the systems particles have not been modified after driver instantiation.
"""
sys_details = SystemSetup()
sys_details.timestep = 0.5 * unit.femtoseconds
sys_details.temperature = 300.0 * unit.kelvin
sys_details.collision_rate = 1.0 / unit.picosecond
sys_details.pressure = 1.0 * unit.atmospheres
sys_details.barostatInterval = 25
sys_details.constraint_tolerance = 1.0e-7
app.Topology.loadBondDefinitions(bonds_path)
# Load pdb file with protons compatible residue names
pdbx = app.PDBxFile(
get_test_data(
"glu_ala_his-solvated-minimized-renamed.cif", "testsystems/tripeptides"
)
)
forcefield = app.ForceField(ffxml_path, ions_spce_path, "spce.xml")
# System Configuration
nonbondedMethod = app.PME
constraints = app.AllBonds
rigidWater = True
sys_details.constraintTolerance = 1.0e-7
# Simulation Options
platform = mm.Platform.getPlatformByName("Reference")
# Prepare the Simulation
topology = pdbx.topology
positions = pdbx.positions
system = forcefield.createSystem(
topology,
nonbondedMethod=nonbondedMethod,
constraints=constraints,
rigidWater=rigidWater,
)
system.addForce(
mm.MonteCarloBarostat(
sys_details.pressure, sys_details.temperature, sys_details.barostatInterval
)
)
integrator = create_compound_gbaoab_integrator(testsystem=sys_details)
original_system = pattern_from_multiline(
mm.XmlSerializer.serialize(system), "<Particle"
)
driver = ForceFieldProtonDrive(
sys_details.temperature,
topology,
system,
forcefield,
ffxml_path,
pressure=sys_details.pressure,
perturbations_per_trial=1,
)
after_driver = pattern_from_multiline(
mm.XmlSerializer.serialize(system), "<Particle"
)
# Clean up so that the classes remain unmodified
# unit test specific errors might occur otherwise when loading files due
# to class side effects
app.Topology.unloadStandardBonds()
# Make sure there are no differences between the particles in each system
assert original_system == after_driver
def test_create_simulation(self):
"""Instantiate a ConstantPHSimulation at 300K/1 atm for a small peptide."""
pdb = app.PDBxFile(
get_test_data("glu_ala_his-solvated-minimized-renamed.cif",
"testsystems/tripeptides"))
forcefield = app.ForceField("amber10-constph.xml", "ions_tip3p.xml",
"tip3p.xml")
system = forcefield.createSystem(
pdb.topology,
nonbondedMethod=app.PME,
nonbondedCutoff=1.0 * unit.nanometers,
constraints=app.HBonds,
rigidWater=True,
ewaldErrorTolerance=0.0005,
)
temperature = 300 * unit.kelvin
integrator = GBAOABIntegrator(
temperature=temperature,
collision_rate=1.0 / unit.picoseconds,
timestep=2.0 * unit.femtoseconds,
constraint_tolerance=1.0e-7,
external_work=False,
)
ncmcintegrator = GBAOABIntegrator(
temperature=temperature,
collision_rate=1.0 / unit.picoseconds,
timestep=2.0 * unit.femtoseconds,
constraint_tolerance=1.0e-7,
external_work=True,
)
compound_integrator = mm.CompoundIntegrator()
compound_integrator.addIntegrator(integrator)
compound_integrator.addIntegrator(ncmcintegrator)
pressure = 1.0 * unit.atmosphere
system.addForce(mm.MonteCarloBarostat(pressure, temperature))
driver = ForceFieldProtonDrive(
temperature,
pdb.topology,
system,
forcefield,
["amber10-constph.xml"],
pressure=pressure,
perturbations_per_trial=0,
)
simulation = app.ConstantPHSimulation(
pdb.topology,
system,
compound_integrator,
driver,
platform=self._default_platform,
)
simulation.context.setPositions(pdb.positions)
simulation.context.setVelocitiesToTemperature(temperature)
# Regular MD step
simulation.step(1)
# Update the titration states using the uniform proposal
simulation.update(1)
print("Done!")
def test_create_constantphcalibration_with_reporters(self):
"""Test running a calibration using constant-pH with reporters."""
pdb = app.PDBxFile(
get_test_data("glu_ala_his-solvated-minimized-renamed.cif",
"testsystems/tripeptides"))
forcefield = app.ForceField("amber10-constph.xml", "ions_tip3p.xml",
"tip3p.xml")
system = forcefield.createSystem(
pdb.topology,
nonbondedMethod=app.PME,
nonbondedCutoff=1.0 * unit.nanometers,
constraints=app.HBonds,
rigidWater=True,
ewaldErrorTolerance=0.0005,
)
temperature = 300 * unit.kelvin
integrator = GBAOABIntegrator(
temperature=temperature,
collision_rate=1.0 / unit.picoseconds,
timestep=2.0 * unit.femtoseconds,
constraint_tolerance=1.0e-7,
external_work=False,
)
ncmcintegrator = GBAOABIntegrator(
temperature=temperature,
collision_rate=1.0 / unit.picoseconds,
timestep=2.0 * unit.femtoseconds,
constraint_tolerance=1.0e-7,
external_work=True,
)
compound_integrator = mm.CompoundIntegrator()
compound_integrator.addIntegrator(integrator)
compound_integrator.addIntegrator(ncmcintegrator)
pressure = 1.0 * unit.atmosphere
system.addForce(mm.MonteCarloBarostat(pressure, temperature))
driver = ForceFieldProtonDrive(
temperature,
pdb.topology,
system,
forcefield,
["amber10-constph.xml"],
pressure=pressure,
perturbations_per_trial=2,
propagations_per_step=1,
)
# prep the driver for calibration
driver.enable_calibration(SAMSApproach.ONESITE, group_index=-1)
simulation = app.ConstantPHSimulation(
pdb.topology,
system,
compound_integrator,
driver,
platform=self._default_platform,
)
simulation.context.setPositions(pdb.positions)
simulation.context.setVelocitiesToTemperature(temperature)
# Outputfile for reporters
newname = uuid4().hex + ".nc"
ncfile = netCDF4.Dataset(newname, "w")
tr = TitrationReporter(ncfile, 1)
mr = MetadataReporter(ncfile)
nr = NCMCReporter(ncfile, 1)
sr = SAMSReporter(ncfile, 1)
simulation.update_reporters.append(tr)
simulation.update_reporters.append(mr)
simulation.update_reporters.append(nr)
simulation.calibration_reporters.append(sr)
simulation.step(1)
# Update the titration states using the uniform proposal
simulation.update(1)
# Adapt the weights using binary update.
simulation.adapt()
# Attempt to prevent segfaults by closing files
ncfile.close()
def test_create_constantphcalibration_resume(self):
"""Test running a calibration using constant-pH."""
pdb = app.PDBxFile(
get_test_data("glu_ala_his-solvated-minimized-renamed.cif",
"testsystems/tripeptides"))
forcefield = app.ForceField("amber10-constph.xml", "ions_tip3p.xml",
"tip3p.xml")
system = forcefield.createSystem(
pdb.topology,
nonbondedMethod=app.PME,
nonbondedCutoff=1.0 * unit.nanometers,
constraints=app.HBonds,
rigidWater=True,
ewaldErrorTolerance=0.0005,
)
temperature = 300 * unit.kelvin
integrator = GBAOABIntegrator(
temperature=temperature,
collision_rate=1.0 / unit.picoseconds,
timestep=2.0 * unit.femtoseconds,
constraint_tolerance=1.0e-7,
external_work=False,
)
ncmcintegrator = GBAOABIntegrator(
temperature=temperature,
collision_rate=1.0 / unit.picoseconds,
timestep=2.0 * unit.femtoseconds,
constraint_tolerance=1.0e-7,
external_work=True,
)
compound_integrator = mm.CompoundIntegrator()
compound_integrator.addIntegrator(integrator)
compound_integrator.addIntegrator(ncmcintegrator)
pressure = 1.0 * unit.atmosphere
system.addForce(mm.MonteCarloBarostat(pressure, temperature))
driver = ForceFieldProtonDrive(
temperature,
pdb.topology,
system,
forcefield,
["amber10-constph.xml"],
pressure=pressure,
perturbations_per_trial=0,
)
driver.enable_calibration(SAMSApproach.ONESITE, group_index=-1)
simulation = app.ConstantPHSimulation(
pdb.topology,
system,
compound_integrator,
driver,
platform=self._default_platform,
)
simulation.context.setPositions(pdb.positions)
simulation.context.setVelocitiesToTemperature(temperature)
simulation.step(1)
# Update the titration states using the uniform proposal
simulation.update(1)
# Adapt the weights using binary update, a few times just to rack up the counters.
for x in range(5):
simulation.adapt()
# retrieve the samsProperties
# TODO use deserialize proton drive for this
xml = simulation.drive.state_to_xml()
driver2 = NCMCProtonDrive(
temperature,
pdb.topology,
system,
pressure=pressure,
perturbations_per_trial=0,
)
driver2.state_from_xml_tree(etree.fromstring(xml))
integrator2 = GBAOABIntegrator(
temperature=temperature,
collision_rate=1.0 / unit.picoseconds,
timestep=2.0 * unit.femtoseconds,
constraint_tolerance=1.0e-7,
external_work=False,
)
ncmcintegrator2 = GBAOABIntegrator(
temperature=temperature,
collision_rate=1.0 / unit.picoseconds,
timestep=2.0 * unit.femtoseconds,
constraint_tolerance=1.0e-7,
external_work=True,
)
compound_integrator2 = mm.CompoundIntegrator()
compound_integrator2.addIntegrator(integrator2)
compound_integrator2.addIntegrator(ncmcintegrator2)
# Make a new calibration and do another step, ignore the state for this example
simulation2 = app.ConstantPHSimulation(
pdb.topology,
system,
compound_integrator2,
driver2,
platform=self._default_platform,
)
assert (simulation2.drive.calibration_state._stage is
simulation.drive.calibration_state._stage)
# get going then
simulation2.context.setPositions(pdb.positions)
simulation2.context.setVelocitiesToTemperature(temperature)
simulation2.step(1)
# Update the titration states using the uniform proposal
simulation2.update(1)
# Adapt the weights using binary update.
simulation2.adapt()
assert (
simulation2.drive.calibration_state._current_adaptation ==
-simulation.drive.calibration_state._min_burn + 6
), "The resumed calibration does not have the right adaptation_index"
def test_create_importance_sampling_reporters(self):
"""Instantiate a ConstantPHSimulation at 300K/1 atm for a small peptide using importance sampling with reporters."""
pdb = app.PDBxFile(
get_test_data("glu_ala_his-solvated-minimized-renamed.cif",
"testsystems/tripeptides"))
forcefield = app.ForceField("amber10-constph.xml", "ions_tip3p.xml",
"tip3p.xml")
system = forcefield.createSystem(
pdb.topology,
nonbondedMethod=app.PME,
nonbondedCutoff=1.0 * unit.nanometers,
constraints=app.HBonds,
rigidWater=True,
ewaldErrorTolerance=0.0005,
)
temperature = 300 * unit.kelvin
integrator = GBAOABIntegrator(
temperature=temperature,
collision_rate=1.0 / unit.picoseconds,
timestep=2.0 * unit.femtoseconds,
constraint_tolerance=1.0e-7,
external_work=False,
)
ncmcintegrator = GBAOABIntegrator(
temperature=temperature,
collision_rate=1.0 / unit.picoseconds,
timestep=2.0 * unit.femtoseconds,
constraint_tolerance=1.0e-7,
external_work=True,
)
compound_integrator = mm.CompoundIntegrator()
compound_integrator.addIntegrator(integrator)
compound_integrator.addIntegrator(ncmcintegrator)
pressure = 1.0 * unit.atmosphere
system.addForce(mm.MonteCarloBarostat(pressure, temperature))
driver = ForceFieldProtonDrive(
temperature,
pdb.topology,
system,
forcefield,
["amber10-constph.xml"],
pressure=pressure,
perturbations_per_trial=0,
sampling_method=SamplingMethod.IMPORTANCE,
)
simulation = app.ConstantPHSimulation(
pdb.topology,
system,
compound_integrator,
driver,
platform=self._default_platform,
)
simulation.context.setPositions(pdb.positions)
simulation.context.setVelocitiesToTemperature(temperature)
newname = uuid4().hex + ".nc"
ncfile = netCDF4.Dataset(newname, "w")
tr = TitrationReporter(ncfile, 1)
mr = MetadataReporter(ncfile)
nr = NCMCReporter(ncfile, 1)
simulation.update_reporters.append(tr)
simulation.update_reporters.append(mr)
simulation.update_reporters.append(nr)
# Regular MD step
simulation.step(1)
# Update the titration states using the uniform proposal
niters = 3
for x in range(niters):
simulation.update(1)
n_total_states = np.product(
[len(group) for group in driver.titrationGroups])
assert (len(ncfile["Protons/Titration/update"][:]) == n_total_states *
niters), "The wrong number of updates were recorded"
work_values = np.split(ncfile["Protons/NCMC/total_work"][:], niters)
init_states = ncfile["Protons/NCMC/initial_state"][:, :]
assert np.all(
init_states == 0), "States should all be zero at the start."
first_run = work_values[0]
assert np.all(np.unique(first_run) == np.sort(
first_run)), "No work values should be duplicated."
# Since instanteneous switching is used, this should be true
for x in range(1, niters):
assert np.all(
np.isclose(work_values[x],
first_run)), "Work should be equal for all states."
# Switch state
driver.set_titration_state(0,
3,
updateContextParameters=True,
updateIons=True)
driver.set_titration_state(1,
1,
updateContextParameters=True,
updateIons=True)
simulation.update(1)
assert (ncfile["Protons/NCMC/initial_state"][-n_total_states, 0] == 3
), "Initial state was not changed correctly."
assert (ncfile["Protons/NCMC/initial_state"][-n_total_states, 1] == 1
), "Initial state was not changed correctly."
work_values = np.split(ncfile["Protons/NCMC/total_work"][:],
niters + 1)
assert not np.all(
np.isclose(work_values[0], work_values[-1])
), "Work values starting from different state should differ."
return
def test_create_importance_sampling(self):
"""Instantiate a ConstantPHSimulation at 300K/1 atm for a small peptide using importance sampling."""
pdb = app.PDBxFile(
get_test_data("glu_ala_his-solvated-minimized-renamed.cif",
"testsystems/tripeptides"))
forcefield = app.ForceField("amber10-constph.xml", "ions_tip3p.xml",
"tip3p.xml")
system = forcefield.createSystem(
pdb.topology,
nonbondedMethod=app.PME,
nonbondedCutoff=1.0 * unit.nanometers,
constraints=app.HBonds,
rigidWater=True,
ewaldErrorTolerance=0.0005,
)
temperature = 300 * unit.kelvin
integrator = GBAOABIntegrator(
temperature=temperature,
collision_rate=1.0 / unit.picoseconds,
timestep=2.0 * unit.femtoseconds,
constraint_tolerance=1.0e-7,
external_work=False,
)
ncmcintegrator = GBAOABIntegrator(
temperature=temperature,
collision_rate=1.0 / unit.picoseconds,
timestep=2.0 * unit.femtoseconds,
constraint_tolerance=1.0e-7,
external_work=True,
)
compound_integrator = mm.CompoundIntegrator()
compound_integrator.addIntegrator(integrator)
compound_integrator.addIntegrator(ncmcintegrator)
pressure = 1.0 * unit.atmosphere
system.addForce(mm.MonteCarloBarostat(pressure, temperature))
driver = ForceFieldProtonDrive(
temperature,
pdb.topology,
system,
forcefield,
["amber10-constph.xml"],
pressure=pressure,
perturbations_per_trial=0,
sampling_method=SamplingMethod.IMPORTANCE,
)
simulation = app.ConstantPHSimulation(
pdb.topology,
system,
compound_integrator,
driver,
platform=self._default_platform,
)
simulation.context.setPositions(pdb.positions)
simulation.context.setVelocitiesToTemperature(temperature)
# Regular MD step
simulation.step(1)
# Update the titration states using the uniform proposal
simulation.update(1)
# Total states is 15 but proposing the same state as current does not get added to statistics.
assert simulation.drive.nattempted == 14, "Not enough switch were attempted."
assert simulation.drive.naccepted == 0, "No acceptance should have occurred."
assert (simulation.drive.nattempted == simulation.drive.nrejected
), "The rejection count should match the number of attempts"
print("Done!")