def restraint_selection_template(topography_ligand_atoms=None,
restrained_receptor_atoms=None,
restrained_ligand_atoms=None,
topography_regions=None):
"""The DSL atom selection works as expected."""
test_system = testsystems.HostGuestVacuum()
topography = Topography(test_system.topology, ligand_atoms=topography_ligand_atoms)
if topography_regions is not None:
for region, selection in topography_regions.items():
topography.add_region(region, selection)
sampler_state = states.SamplerState(positions=test_system.positions)
thermodynamic_state = states.ThermodynamicState(test_system.system,
temperature=300.0 * unit.kelvin)
# Initialize with DSL and without processing the string raises an error.
restraint = yank.restraints.Harmonic(spring_constant=2.0 * unit.kilojoule_per_mole / unit.nanometer ** 2,
restrained_receptor_atoms=restrained_receptor_atoms,
restrained_ligand_atoms=restrained_ligand_atoms)
with nose.tools.assert_raises(yank.restraints.RestraintParameterError):
restraint.restrain_state(thermodynamic_state)
# After parameter determination, the indices of the restrained atoms are correct.
restraint.determine_missing_parameters(thermodynamic_state, sampler_state, topography)
assert len(restraint.restrained_receptor_atoms) == 14
assert len(restraint.restrained_ligand_atoms) == 30
# The bond force is configured correctly.
restraint.restrain_state(thermodynamic_state)
system = thermodynamic_state.system
for force in system.getForces():
if isinstance(force, openmm.CustomCentroidBondForce):
assert force.getBondParameters(0)[0] == (0, 1)
assert len(force.getGroupParameters(0)[0]) == 14
assert len(force.getGroupParameters(1)[0]) == 30
assert isinstance(force, openmm.CustomCentroidBondForce) # We have found a force.
def restraint_selection_template(topography_ligand_atoms=None,
restrained_receptor_atoms=None,
restrained_ligand_atoms=None,
topography_regions=None):
"""The DSL atom selection works as expected."""
test_system = testsystems.HostGuestVacuum()
topography = Topography(test_system.topology, ligand_atoms=topography_ligand_atoms)
if topography_regions is not None:
for region, selection in topography_regions.items():
topography.add_region(region, selection)
sampler_state = states.SamplerState(positions=test_system.positions)
thermodynamic_state = states.ThermodynamicState(test_system.system,
temperature=300.0 * unit.kelvin)
# Initialize with DSL and without processing the string raises an error.
restraint = yank.restraints.Harmonic(spring_constant=2.0 * unit.kilojoule_per_mole / unit.nanometer ** 2,
restrained_receptor_atoms=restrained_receptor_atoms,
restrained_ligand_atoms=restrained_ligand_atoms)
with nose.tools.assert_raises(yank.restraints.RestraintParameterError):
restraint.restrain_state(thermodynamic_state)
# After parameter determination, the indices of the restrained atoms are correct.
restraint.determine_missing_parameters(thermodynamic_state, sampler_state, topography)
assert len(restraint.restrained_receptor_atoms) == 14
assert len(restraint.restrained_ligand_atoms) == 30
# The bond force is configured correctly.
restraint.restrain_state(thermodynamic_state)
system = thermodynamic_state.system
for force in system.getForces():
if isinstance(force, openmm.CustomCentroidBondForce):
assert force.getBondParameters(0)[0] == (0, 1)
assert len(force.getGroupParameters(0)[0]) == 14
assert len(force.getGroupParameters(1)[0]) == 30
assert isinstance(force, openmm.CustomCentroidBondForce) # We have found a force.
def test_harmonic_standard_state():
"""
Test that the expected harmonic standard state correction is close to our approximation
Also ensures that PBC bonds are being computed and disabled correctly as expected
"""
LJ_fluid = testsystems.LennardJonesFluid()
# Create Harmonic restraint.
restraint = yank.restraints.create_restraint('Harmonic',
restrained_receptor_atoms=1)
# Determine other parameters.
ligand_atoms = [3, 4, 5]
topography = Topography(LJ_fluid.topology, ligand_atoms=ligand_atoms)
sampler_state = states.SamplerState(positions=LJ_fluid.positions)
thermodynamic_state = states.ThermodynamicState(system=LJ_fluid.system,
temperature=300.0 *
unit.kelvin)
restraint.determine_missing_parameters(thermodynamic_state, sampler_state,
topography)
spring_constant = restraint.spring_constant
# Compute standard-state volume for a single molecule in a box of size (1 L) / (avogadros number)
liter = 1000.0 * unit.centimeters**3 # one liter
box_volume = liter / (unit.AVOGADRO_CONSTANT_NA * unit.mole
) # standard state volume
analytical_shell_volume = (
2 * math.pi / (spring_constant * thermodynamic_state.beta))**(3.0 / 2)
analytical_standard_state_G = -math.log(
box_volume / analytical_shell_volume)
restraint_standard_state_G = restraint.get_standard_state_correction(
thermodynamic_state)
np.testing.assert_allclose(analytical_standard_state_G,
restraint_standard_state_G)
def setup_class(cls):
lysozyme = testsystems.LysozymeImplicit()
system, positions = lysozyme.system, lysozyme.positions
thermodynamic_state = states.ThermodynamicState(system, 300*unit.kelvin)
sampler_state = states.SamplerState(positions)
topography = Topography(lysozyme.topology, ligand_atoms='resname TMP')
cls.lysozyme_test_case = (thermodynamic_state, sampler_state, topography)
def test_BoreschLike_standard_state_analytical():
"""
Perform some analytical tests of the Boresch standard state correction.
Also ensures that PBC is being handled correctly
"""
LJ_fluid = testsystems.LennardJonesFluid()
# Define receptor and ligand atoms
receptor_atoms = [0, 1, 2]
ligand_atoms = [3, 4, 5]
# Create restraint
K_r = 1.0 * unit.kilocalories_per_mole / unit.angstrom**2
r_0 = 0.0 * unit.angstrom
K_theta = 0.0 * unit.kilocalories_per_mole / unit.degrees**2
theta_0 = 30.0 * unit.degrees
topography = Topography(LJ_fluid.topology, ligand_atoms=ligand_atoms)
sampler_state = states.SamplerState(positions=LJ_fluid.positions)
thermodynamic_state = states.ThermodynamicState(system=LJ_fluid.system,
temperature=300.0 *
unit.kelvin)
for restraint_name in ['Boresch', 'PeriodicTorsionBoresch']:
restraint = yank.restraints.create_restraint(
'Boresch',
restrained_receptor_atoms=receptor_atoms,
restrained_ligand_atoms=ligand_atoms,
K_r=K_r,
r_aA0=r_0,
K_thetaA=K_theta,
theta_A0=theta_0,
K_thetaB=K_theta,
theta_B0=theta_0,
K_phiA=K_theta,
phi_A0=theta_0,
K_phiB=K_theta,
phi_B0=theta_0,
K_phiC=K_theta,
phi_C0=theta_0)
# Determine other parameters
restraint.determine_missing_parameters(thermodynamic_state,
sampler_state, topography)
# Compute standard-state volume for a single molecule in a box of size (1 L) / (avogadros number)
liter = 1000.0 * unit.centimeters**3 # one liter
box_volume = liter / (unit.AVOGADRO_CONSTANT_NA * unit.mole
) # standard state volume
analytical_shell_volume = (2 * math.pi /
(K_r * thermodynamic_state.beta))**(3.0 / 2)
analytical_standard_state_G = -math.log(
box_volume / analytical_shell_volume)
restraint_standard_state_G = restraint.get_standard_state_correction(
thermodynamic_state)
msg = 'Failed test for restraint {}'.format(restraint_name)
np.testing.assert_allclose(analytical_standard_state_G,
restraint_standard_state_G,
err_msg=msg)
def test_partial_parametrization():
"""The automatic restraint parametrization doesn't overwrite user values."""
# Create states and identify ligand/receptor.
test_system = testsystems.HostGuestVacuum()
topography = Topography(test_system.topology, ligand_atoms='resname B2')
sampler_state = states.SamplerState(positions=test_system.positions)
thermodynamic_state = states.ThermodynamicState(test_system.system,
temperature=300.0*unit.kelvin)
# Test case: (restraint_type, constructor_kwargs)
boresch = dict(restrained_ligand_atoms=[130, 131, 136], K_r=1.0*unit.kilojoule_per_mole/unit.angstroms**2)
test_cases = [
('Harmonic', dict(spring_constant=2.0*unit.kilojoule_per_mole/unit.nanometer**2,
restrained_receptor_atoms=[5])),
('FlatBottom', dict(well_radius=1.0*unit.angstrom, restrained_ligand_atoms=[130])),
('Boresch', boresch),
('PeriodicTorsionBoresch', boresch),
]
if OpenMM73.dev_validate:
test_cases.append(('RMSD', dict(restrained_ligand_atoms=[130, 131, 136],
K_RMSD=1.0 * unit.kilojoule_per_mole / unit.angstroms ** 2)))
for restraint_type, kwargs in test_cases:
state = copy.deepcopy(thermodynamic_state)
restraint = yank.restraints.create_restraint(restraint_type, **kwargs)
# Test-precondition: The restraint has undefined parameters.
with nose.tools.assert_raises(yank.restraints.RestraintParameterError):
restraint.restrain_state(state)
# The automatic parametrization maintains user values.
restraint.determine_missing_parameters(state, sampler_state, topography)
for parameter_name, parameter_value in kwargs.items():
assert getattr(restraint, parameter_name) == parameter_value
# The rest of the parameters has been determined.
restraint.get_standard_state_correction(state)
# The force has been configured correctly.
restraint.restrain_state(state)
system = state.system
for force in system.getForces():
# RadiallySymmetricRestraint between two single atoms.
if isinstance(force, openmm.CustomBondForce):
particle1, particle2, _ = force.getBondParameters(0)
assert particle1 == restraint.restrained_receptor_atoms[0]
assert particle2 == restraint.restrained_ligand_atoms[0]
# Boresch restraint.
elif isinstance(force, openmm.CustomCompoundBondForce):
particles, _ = force.getBondParameters(0)
assert particles == tuple(restraint.restrained_receptor_atoms + restraint.restrained_ligand_atoms)
# RMSD restraint.
elif OpenMM73.dev_validate and isinstance(force, openmm.CustomCVForce):
rmsd_cv = force.getCollectiveVariable(0)
particles = rmsd_cv.getParticles()
assert particles == tuple(restraint.restrained_receptor_atoms + restraint.restrained_ligand_atoms)
def build_test_case():
"""Create a new ThermodynamicState, SamplerState and Topography."""
# Create a test system
t = HostGuestNoninteracting()
# Create states and topography encoding the info to determine the parameters.
topography = Topography(t.topology, ligand_atoms='resname B2')
sampler_state = states.SamplerState(positions=t.positions)
thermodynamic_state = states.ThermodynamicState(system=t.system, temperature=300.0*unit.kelvin)
return thermodynamic_state, sampler_state, topography
