def run_without_work_accumulation(
self,
testsystem,
parameter_name,
parameter_initial,
parameter_final,
platform_name="Reference",
name=None,
):
"""Compare external work accumulation between Reference and CPU platforms.
"""
if name is None:
name = testsystem.name
from openmmtools.constants import kB
system, topology = testsystem.system, testsystem.topology
temperature = 298.0 * unit.kelvin
platform = openmm.Platform.getPlatformByName(platform_name)
# TODO: Set precision and determinism if platform is ['OpenCL', 'CUDA']
nsteps = 20
kT = kB * temperature
integrator = GBAOABIntegrator(temperature=temperature, external_work=False)
context = openmm.Context(system, integrator, platform)
context.setParameter(parameter_name, parameter_initial)
context.setPositions(testsystem.positions)
context.setVelocitiesToTemperature(temperature)
integrator.step(1)
for step in range(nsteps):
lambda_value = float(step + 1) / float(nsteps)
parameter_value = (
parameter_initial * (1 - lambda_value) + parameter_final * lambda_value
)
initial_energy = context.getState(getEnergy=True).getPotentialEnergy()
context.setParameter(parameter_name, parameter_value)
final_energy = context.getState(getEnergy=True).getPotentialEnergy()
integrator.step(1)
del context, integrator
def run_without_work_accumulation(
self,
testsystem,
parameter_name,
parameter_initial,
parameter_final,
platform_name="Reference",
name=None,
):
"""Compare external work accumulation between Reference and CPU platforms.
"""
if name is None:
name = testsystem.name
from openmmtools.constants import kB
system, topology = testsystem.system, testsystem.topology
temperature = 298.0 * unit.kelvin
platform = openmm.Platform.getPlatformByName(platform_name)
# TODO: Set precision and determinism if platform is ['OpenCL', 'CUDA']
nsteps = 20
kT = kB * temperature
integrator = GBAOABIntegrator(temperature=temperature,
external_work=False)
context = openmm.Context(system, integrator, platform)
context.setParameter(parameter_name, parameter_initial)
context.setPositions(testsystem.positions)
context.setVelocitiesToTemperature(temperature)
integrator.step(1)
for step in range(nsteps):
lambda_value = float(step + 1) / float(nsteps)
parameter_value = (parameter_initial * (1 - lambda_value) +
parameter_final * lambda_value)
initial_energy = context.getState(
getEnergy=True).getPotentialEnergy()
context.setParameter(parameter_name, parameter_value)
final_energy = context.getState(
getEnergy=True).getPotentialEnergy()
integrator.step(1)
del context, integrator
def compare_external_protocol_work_accumulation(
self,
testsystem,
parameter_name,
parameter_initial,
parameter_final,
platform_name="Reference",
name=None,
):
"""Compare external work accumulation between Reference and CPU platforms.
"""
if name is None:
name = testsystem.name
from openmmtools.constants import kB
system, topology = testsystem.system, testsystem.topology
temperature = 298.0 * unit.kelvin
platform = openmm.Platform.getPlatformByName(platform_name)
# TODO: Set precision and determinism if platform is ['OpenCL', 'CUDA']
nsteps = 20
kT = kB * temperature
integrator = GBAOABIntegrator(temperature=temperature)
context = openmm.Context(system, integrator, platform)
context.setParameter(parameter_name, parameter_initial)
context.setPositions(testsystem.positions)
context.setVelocitiesToTemperature(temperature)
assert (
integrator.getGlobalVariableByName("protocol_work") == 0
), "Protocol work should be 0 initially"
integrator.step(1)
assert (
integrator.getGlobalVariableByName("protocol_work") == 0
), "There should be no protocol work."
external_protocol_work = 0.0
for step in range(nsteps):
lambda_value = float(step + 1) / float(nsteps)
parameter_value = (
parameter_initial * (1 - lambda_value) + parameter_final * lambda_value
)
initial_energy = context.getState(getEnergy=True).getPotentialEnergy()
context.setParameter(parameter_name, parameter_value)
final_energy = context.getState(getEnergy=True).getPotentialEnergy()
external_protocol_work += (final_energy - initial_energy) / kT
integrator.step(1)
integrator_protocol_work = (
integrator.getGlobalVariableByName("protocol_work")
* unit.kilojoules_per_mole
/ kT
)
message = "\n"
message += "protocol work discrepancy noted for %s on platform %s\n" % (
name,
platform_name,
)
message += (
"step %5d : external %16e kT | integrator %16e kT | difference %16e kT"
% (
step,
external_protocol_work,
integrator_protocol_work,
external_protocol_work - integrator_protocol_work,
)
)
# Test relative tolerance
assert (
pytest.approx(external_protocol_work, 0.001) == integrator_protocol_work
), message
del context, integrator
def compare_external_protocol_work_accumulation(
self,
testsystem,
parameter_name,
parameter_initial,
parameter_final,
platform_name="Reference",
name=None,
):
"""Compare external work accumulation between Reference and CPU platforms.
"""
if name is None:
name = testsystem.name
from openmmtools.constants import kB
system, topology = testsystem.system, testsystem.topology
temperature = 298.0 * unit.kelvin
platform = openmm.Platform.getPlatformByName(platform_name)
# TODO: Set precision and determinism if platform is ['OpenCL', 'CUDA']
nsteps = 20
kT = kB * temperature
integrator = GBAOABIntegrator(temperature=temperature)
context = openmm.Context(system, integrator, platform)
context.setParameter(parameter_name, parameter_initial)
context.setPositions(testsystem.positions)
context.setVelocitiesToTemperature(temperature)
assert (integrator.getGlobalVariableByName("protocol_work") == 0
), "Protocol work should be 0 initially"
integrator.step(1)
assert (integrator.getGlobalVariableByName("protocol_work") == 0
), "There should be no protocol work."
external_protocol_work = 0.0
for step in range(nsteps):
lambda_value = float(step + 1) / float(nsteps)
parameter_value = (parameter_initial * (1 - lambda_value) +
parameter_final * lambda_value)
initial_energy = context.getState(
getEnergy=True).getPotentialEnergy()
context.setParameter(parameter_name, parameter_value)
final_energy = context.getState(
getEnergy=True).getPotentialEnergy()
external_protocol_work += (final_energy - initial_energy) / kT
integrator.step(1)
integrator_protocol_work = (
integrator.getGlobalVariableByName("protocol_work") *
unit.kilojoules_per_mole / kT)
message = "\n"
message += "protocol work discrepancy noted for %s on platform %s\n" % (
name,
platform_name,
)
message += (
"step %5d : external %16e kT | integrator %16e kT | difference %16e kT"
% (
step,
external_protocol_work,
integrator_protocol_work,
external_protocol_work - integrator_protocol_work,
))
# Test relative tolerance
assert (pytest.approx(external_protocol_work,
0.001) == integrator_protocol_work), message
del context, integrator
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!")