def test_system_charge_reporting(self):
"""Test if the system_charge is correctly reported."""
pdb = app.PDBxFile(
get_test_data("glu_ala_his-solvated-minimized-renamed.cif",
"testsystems/tripeptides"))
initial_charge = (
0
) # Ion totals are 0, and the system starts in state 0 for both, GLU deprotonated, HIS protonated
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,
)
# pools defined by their residue index for convenience later on
driver.define_pools({"0": [0], "1": [1]})
simulation = app.ConstantPHSimulation(
pdb.topology,
system,
compound_integrator,
driver,
platform=self._default_platform,
)
simulation.context.setPositions(pdb.positions)
simulation.context.setVelocitiesToTemperature(temperature)
filename = uuid.uuid4().hex + ".nc"
ncfile = netCDF4.Dataset(filename, "w")
print("Temporary file: ", filename)
newreporter = tr.TitrationReporter(ncfile, 2)
simulation.update_reporters.append(newreporter)
# Regular MD step
simulation.step(1)
# Update the titration states forcibly from a pregenerated series
glu_states = np.asarray([
1, 4, 4, 1, 0, 2, 0, 2, 4, 3, 2, 1, 0, 2, 0, 0, 0, 0, 0, 0, 1, 2,
1, 3, 1
])
his_states = np.asarray([
2, 1, 0, 1, 2, 2, 1, 2, 2, 1, 0, 2, 2, 1, 2, 2, 2, 2, 2, 2, 0, 2,
2, 2, 1
])
for i in range(len(glu_states)):
simulation.drive.set_titration_state(0,
glu_states[i],
updateContextParameters=False)
simulation.drive.set_titration_state(1,
his_states[i],
updateContextParameters=False)
simulation.update_reporters[0].report(simulation)
tot_charge = 0
for resi, residue in enumerate(simulation.drive.titrationGroups):
icharge = int(floor(0.5 + residue.total_charge))
tot_charge += icharge
assert (
ncfile["Protons/Titration/{}_charge".format(resi)][i] ==
icharge), "Residue charge is not recorded correctly."
assert (
ncfile["Protons/Titration/complex_charge"][i] == tot_charge
), "The recorded complex total charge does not match the actual charge."
# close files to avoid segfaults, possibly
ncfile.close()
def test_atom_status_reporting(self):
"""Test if the atom_status is correctly reported."""
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)
filename = uuid.uuid4().hex + ".nc"
ncfile = netCDF4.Dataset(filename, "w")
print("Temporary file: ", filename)
newreporter = tr.TitrationReporter(ncfile, 2)
simulation.update_reporters.append(newreporter)
# Regular MD step
simulation.step(1)
# Update the titration states forcibly from a pregenerated series
glu_states = np.asarray([
1, 4, 4, 1, 0, 2, 0, 2, 4, 3, 2, 1, 0, 2, 0, 0, 0, 0, 0, 0, 1, 2,
1, 3, 1
])
his_states = np.asarray([
2, 1, 0, 1, 2, 2, 1, 2, 2, 1, 0, 2, 2, 1, 2, 2, 2, 2, 2, 2, 0, 2,
2, 2, 1
])
for i in range(len(glu_states)):
simulation.drive.set_titration_state(0,
glu_states[i],
updateContextParameters=False)
simulation.drive.set_titration_state(1,
his_states[i],
updateContextParameters=False)
simulation.update_reporters[0].report(simulation)
# check glu
self._verify_atom_status(i, 0, ncfile, simulation)
# check his
self._verify_atom_status(i, 1, ncfile, simulation)
ncfile.close()
def test_reports(self):
"""Instantiate a simulation at 300K/1 atm for a small peptide with reporter."""
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=3,
)
# prep the driver for calibration
driver.enable_calibration(
SAMSApproach.ONESITE, group_index=1, update_rule=UpdateRule.BINARY
)
calibration = app.ConstantPHSimulation(
pdb.topology,
system,
compound_integrator,
driver,
platform=self._default_platform,
)
calibration.context.setPositions(pdb.positions)
calibration.context.setVelocitiesToTemperature(temperature)
filename = uuid.uuid4().hex + ".nc"
print("Temporary file: ", filename)
newreporter = sr.SAMSReporter(filename, 2)
calibration.calibration_reporters.append(newreporter)
# Regular MD step
for iteration in range(4):
calibration.step(1)
# Update the titration states using the uniform proposal
calibration.update(1)
# adapt sams weights
calibration.adapt()
# Basic checks for dimension
assert (
newreporter.ncfile["Protons/SAMS"].dimensions["adaptation"].size == 2
), "There should be 2 updates recorded."
assert (
newreporter.ncfile["Protons/SAMS"].dimensions["state"].size == 3
), "There should be 3 states reported."
newreporter.ncfile.close()
def test_reports(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"))
num_atoms = pdb.topology.getNumAtoms()
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,
)
num_titratable = len(driver.titrationGroups)
simulation = app.ConstantPHSimulation(
pdb.topology,
system,
compound_integrator,
driver,
platform=self._default_platform,
)
simulation.context.setPositions(pdb.positions)
simulation.context.setVelocitiesToTemperature(temperature)
filename = uuid.uuid4().hex + ".nc"
print("Temporary file: ", filename)
newreporter = tr.TitrationReporter(filename, 2)
simulation.update_reporters.append(newreporter)
# Regular MD step
simulation.step(1)
# Update the titration states using the uniform proposal
simulation.update(6)
# Basic checks for dimension
assert (newreporter.ncfile["Protons/Titration"].dimensions["update"].
size == 3), "There should be 3 updates recorded."
assert (
newreporter.ncfile["Protons/Titration"].dimensions["residue"].size
== num_titratable
), "There should be {} residues recorded.".format(num_titratable)
assert (
newreporter.ncfile["Protons/Titration"].dimensions["atom"].size ==
num_atoms), "There should be {} atoms recorded.".format(num_atoms)
newreporter.ncfile.close()
def test_reports_every_perturbation_saltswap(self):
"""Instantiate a ConstantPHSimulation at 300K/1 atm for a small peptide, save every perturbation step, with saltswap."""
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=3,
)
simulation = app.ConstantPHSimulation(
pdb.topology,
system,
compound_integrator,
driver,
platform=self._default_platform,
)
simulation.context.setPositions(pdb.positions)
simulation.context.setVelocitiesToTemperature(temperature)
filename = uuid.uuid4().hex + ".nc"
print("Temporary file: ", filename)
# The salinator initializes the system salts
salinator = Salinator(
context=simulation.context,
system=simulation.system,
topology=simulation.topology,
ncmc_integrator=simulation.integrator.getIntegrator(1),
salt_concentration=0.2 * unit.molar,
pressure=pressure,
temperature=temperature,
)
salinator.neutralize()
salinator.initialize_concentration()
swapper = salinator.swapper
driver.enable_neutralizing_ions(swapper)
newreporter = ncr.NCMCReporter(filename, 1, cumulativeworkInterval=1)
simulation.update_reporters.append(newreporter)
# Regular MD step
simulation.step(1)
# Update the titration states using the uniform proposal
simulation.update(4)
# Basic checks for dimension
assert (newreporter.ncfile["Protons/NCMC"].dimensions["update"].size ==
4), "There should be 4 updates recorded."
assert (newreporter.ncfile["Protons/NCMC"].dimensions["residue"].size
== 2), "There should be 2 residues recorded."
assert (newreporter.ncfile["Protons/NCMC"].dimensions["perturbation"].
size == 3), "There should be max 3 perturbations recorded."
assert (newreporter.ncfile["Protons/NCMC"].dimensions["ion_site"].size
== 1269), "The system should have 1269 potential ion sites."
# Ensure clean exit
newreporter.ncfile.sync()
newreporter.ncfile.close()