def compare_energy_components(rest_system,
other_system,
positions,
platform=REFERENCE_PLATFORM):
"""
Get energy components of a given system
"""
platform = configure_platform(platform)
# Create thermodynamic state and sampler state for non-rest system
thermostate_other = ThermodynamicState(system=other_system,
temperature=temperature)
# Create context for non-rest system
integrator_other = openmm.VerletIntegrator(1.0 * unit.femtosecond)
context_other = thermostate_other.create_context(integrator_other)
context_other.setPositions(positions)
# Get energy components for non-rest system
components_other = [
component[1]
for component in compute_potential_components(context_other, beta=beta)
]
# Create thermodynamic state for rest_system
thermostate_rest = ThermodynamicState(system=rest_system,
temperature=temperature)
# Create context forrest system
integrator_rest = openmm.VerletIntegrator(1.0 * unit.femtosecond)
context_rest = thermostate_rest.create_context(integrator_rest)
context_rest.setPositions(positions)
# Get energy components for rest system
components_rest = [
component[1]
for component in compute_potential_components(context_rest, beta=beta)
]
# Check that bond, angle, and torsion energies match
for other, rest in zip(components_other[:3], components_rest[:3]):
assert np.isclose(
[other], [rest]
), f"The energies do not match for the {other[0]}: {other[1]} (other system) vs. {rest[1]} (REST system)"
# Check that nonbonded energies match
print(components_rest)
nonbonded_other = np.array(components_other[3:]).sum()
nonbonded_rest = np.array(components_rest[3:]).sum()
assert np.isclose(
[nonbonded_other], [nonbonded_rest]
), f"The energies do not match for the NonbondedForce: {nonbonded_other} (other system) vs. {nonbonded_rest} (REST system)"
def test_mutate_quick():
"""
Abbreviated version of test_mutate_all for travis.
"""
import perses.rjmc.topology_proposal as topology_proposal
import perses.rjmc.geometry as geometry
from perses.tests.utils import compute_potential_components
from openmmtools import testsystems as ts
geometry_engine = geometry.FFAllAngleGeometryEngine()
aminos = ['ALA','VAL','GLY','PHE','PRO','TRP']
for aa in aminos:
topology, positions = _get_capped_amino_acid(amino_acid=aa)
modeller = app.Modeller(topology, positions)
ff_filename = "amber99sbildn.xml"
max_point_mutants = 1
ff = app.ForceField(ff_filename)
system = ff.createSystem(modeller.topology)
chain_id = '1'
system_generator = topology_proposal.SystemGenerator([ff_filename])
pm_top_engine = topology_proposal.PointMutationEngine(modeller.topology, system_generator, chain_id, max_point_mutants=max_point_mutants)
current_system = system
current_topology = modeller.topology
current_positions = modeller.positions
minimize_integrator = openmm.VerletIntegrator(1.0*unit.femtosecond)
platform = openmm.Platform.getPlatformByName("Reference")
minimize_context = openmm.Context(current_system, minimize_integrator, platform)
minimize_context.setPositions(current_positions)
initial_state = minimize_context.getState(getEnergy=True)
initial_potential = initial_state.getPotentialEnergy()
openmm.LocalEnergyMinimizer.minimize(minimize_context)
final_state = minimize_context.getState(getEnergy=True, getPositions=True)
final_potential = final_state.getPotentialEnergy()
current_positions = final_state.getPositions()
print("Minimized initial structure from %s to %s" % (str(initial_potential), str(final_potential)))
for k, proposed_amino in enumerate(aminos):
pm_top_engine._allowed_mutations = [[('2',proposed_amino)]]
pm_top_proposal = pm_top_engine.propose(current_system, current_topology)
new_positions, logp = geometry_engine.propose(pm_top_proposal, current_positions, beta)
new_system = pm_top_proposal.new_system
if np.isnan(logp):
raise Exception("NaN in the logp")
integrator = openmm.VerletIntegrator(1*unit.femtoseconds)
platform = openmm.Platform.getPlatformByName("Reference")
context = openmm.Context(new_system, integrator, platform)
context.setPositions(new_positions)
state = context.getState(getEnergy=True)
print(compute_potential_components(context))
potential = state.getPotentialEnergy()
potential_without_units = potential / potential.unit
print(str(potential))
if np.isnan(potential_without_units):
raise Exception("Energy after proposal is NaN")
def test_mutate_quick():
"""
Abbreviated version of test_mutate_all for travis.
"""
import perses.rjmc.topology_proposal as topology_proposal
import perses.rjmc.geometry as geometry
from perses.tests.utils import compute_potential_components
from openmmtools import testsystems as ts
geometry_engine = geometry.FFAllAngleGeometryEngine()
aminos = ['ALA','VAL','GLY','PHE','PRO','TRP']
for aa in aminos:
topology, positions = _get_capped_amino_acid(amino_acid=aa)
modeller = app.Modeller(topology, positions)
ff_filename = "amber99sbildn.xml"
max_point_mutants = 1
ff = app.ForceField(ff_filename)
system = ff.createSystem(modeller.topology)
chain_id = '1'
system_generator = topology_proposal.SystemGenerator([ff_filename])
pm_top_engine = topology_proposal.PointMutationEngine(modeller.topology, system_generator, chain_id, max_point_mutants=max_point_mutants)
current_system = system
current_topology = modeller.topology
current_positions = modeller.positions
minimize_integrator = openmm.VerletIntegrator(1.0*unit.femtosecond)
platform = openmm.Platform.getPlatformByName("Reference")
minimize_context = openmm.Context(current_system, minimize_integrator, platform)
minimize_context.setPositions(current_positions)
initial_state = minimize_context.getState(getEnergy=True)
initial_potential = initial_state.getPotentialEnergy()
openmm.LocalEnergyMinimizer.minimize(minimize_context)
final_state = minimize_context.getState(getEnergy=True, getPositions=True)
final_potential = final_state.getPotentialEnergy()
current_positions = final_state.getPositions()
print("Minimized initial structure from %s to %s" % (str(initial_potential), str(final_potential)))
for k, proposed_amino in enumerate(aminos):
pm_top_engine._allowed_mutations = [[('2',proposed_amino)]]
pm_top_proposal = pm_top_engine.propose(current_system, current_topology)
new_positions, logp = geometry_engine.propose(pm_top_proposal, current_positions, beta)
new_system = pm_top_proposal.new_system
if np.isnan(logp):
raise Exception("NaN in the logp")
integrator = openmm.VerletIntegrator(1*unit.femtoseconds)
platform = openmm.Platform.getPlatformByName("Reference")
context = openmm.Context(new_system, integrator, platform)
context.setPositions(new_positions)
state = context.getState(getEnergy=True)
print(compute_potential_components(context))
potential = state.getPotentialEnergy()
potential_without_units = potential / potential.unit
print(str(potential))
if np.isnan(potential_without_units):
raise Exception("Energy after proposal is NaN")
def test_run_geometry_engine(index=0):
"""
Run the geometry engine a few times to make sure that it actually runs
without exceptions. Convert n-pentane to 2-methylpentane
"""
import logging
logging.basicConfig(level=logging.DEBUG)
import copy
#molecule_name_1 = 'glycine'
#molecule_name_2 = 'tryptophan'
molecule_name_1 = 'erlotinib'
molecule_name_2 = 'imatinib'
molecule1 = generate_initial_molecule(molecule_name_1)
molecule2 = generate_initial_molecule(molecule_name_2)
new_to_old_atom_mapping = align_molecules(molecule1, molecule2)
sys1, pos1, top1 = oemol_to_openmm_system(molecule1, molecule_name_1)
sys2, pos2, top2 = oemol_to_openmm_system(molecule2, molecule_name_2)
import perses.rjmc.geometry as geometry
import perses.rjmc.topology_proposal as topology_proposal
from perses.tests.utils import compute_potential_components
sm_top_proposal = topology_proposal.TopologyProposal(new_topology=top2, new_system=sys2, old_topology=top1, old_system=sys1,
old_chemical_state_key='',new_chemical_state_key='', logp_proposal=0.0, new_to_old_atom_map=new_to_old_atom_mapping, metadata={'test':0.0})
sm_top_proposal._beta = beta
geometry_engine = geometry.FFAllAngleGeometryEngine({'test': 'true', 'reference_positions':pos2})
# Turn on PDB file writing.
geometry_engine.write_proposal_pdb = True
geometry_engine.pdb_filename_prefix = 'geometry-proposal'
test_pdb_file = open("erlotinib_to_imatinib_0%d_0_nosterics.pdb" % index, 'w')
valence_system = copy.deepcopy(sys2)
valence_system.removeForce(3)
valence_system.removeForce(3)
integrator = openmm.VerletIntegrator(1*unit.femtoseconds)
integrator_1 = openmm.VerletIntegrator(1*unit.femtoseconds)
ctx_1 = openmm.Context(sys1, integrator_1)
ctx_1.setPositions(pos1)
ctx_1.setVelocitiesToTemperature(300*unit.kelvin)
integrator_1.step(1000)
pos1_new = ctx_1.getState(getPositions=True).getPositions(asNumpy=True)
context = openmm.Context(sys2, integrator)
context.setPositions(pos2)
state = context.getState(getEnergy=True)
print("Energy before proposal is: %s" % str(state.getPotentialEnergy()))
openmm.LocalEnergyMinimizer.minimize(context)
new_positions, logp_proposal = geometry_engine.propose(sm_top_proposal, pos1_new, beta)
geometry_engine.logp_reverse(sm_top_proposal, new_positions, pos1, beta)
app.PDBFile.writeFile(top2, new_positions, file=test_pdb_file)
test_pdb_file.close()
context.setPositions(new_positions)
state2 = context.getState(getEnergy=True)
print("Energy after proposal is: %s" %str(state2.getPotentialEnergy()))
print(compute_potential_components(context))
valence_integrator = openmm.VerletIntegrator(1*unit.femtoseconds)
platform = openmm.Platform.getPlatformByName("Reference")
valence_ctx = openmm.Context(valence_system, valence_integrator, platform)
valence_ctx.setPositions(new_positions)
vstate = valence_ctx.getState(getEnergy=True)
print("Valence energy after proposal is %s " % str(vstate.getPotentialEnergy()))
final_potential = state2.getPotentialEnergy()
return final_potential / final_potential.unit
def test_mutate_from_all_to_all():
"""
Make sure mutations are successful between every possible pair of before-and-after residues
Mutate Ecoli F-ATPase alpha subunit to all 20 amino acids (test going FROM all possibilities)
Mutate each residue to all 19 alternatives
"""
import perses.rjmc.topology_proposal as topology_proposal
import perses.rjmc.geometry as geometry
from perses.tests.utils import compute_potential_components
from openmmtools import testsystems as ts
geometry_engine = geometry.FFAllAngleGeometryEngine()
aminos = ['ALA','ARG','ASN','ASP','CYS','GLN','GLU','GLY','HIS','ILE','LEU','LYS','MET','PHE','PRO','SER','THR','TRP','TYR','VAL']
for aa in aminos:
topology, positions = _get_capped_amino_acid(amino_acid=aa)
modeller = app.Modeller(topology, positions)
ff_filename = "amber99sbildn.xml"
max_point_mutants = 1
ff = app.ForceField(ff_filename)
system = ff.createSystem(modeller.topology)
chain_id = 'A'
system_generator = topology_proposal.SystemGenerator([ff_filename])
pm_top_engine = topology_proposal.PointMutationEngine(system_generator, chain_id, max_point_mutants=max_point_mutants)
current_system = system
current_topology = modeller.topology
current_positions = modeller.positions
minimize_integrator = openmm.VerletIntegrator(1.0*unit.femtosecond)
platform = openmm.Platform.getPlatformByName("Reference")
minimize_context = openmm.Context(current_system, minimize_integrator, platform)
minimize_context.setPositions(current_positions)
initial_state = minimize_context.getState(getEnergy=True)
initial_potential = initial_state.getPotentialEnergy()
openmm.LocalEnergyMinimizer.minimize(minimize_context)
final_state = minimize_context.getState(getEnergy=True, getPositions=True)
final_potential = final_state.getPotentialEnergy()
current_positions = final_state.getPositions()
print("Minimized initial structure from %s to %s" % (str(initial_potential), str(final_potential)))
for k, proposed_amino in enumerate(aminos):
pm_top_engine._allowed_mutations = [[('2',proposed_amino)]]
pm_top_proposal = pm_top_engine.propose(current_system, current_topology)
new_positions, logp = geometry_engine.propose(pm_top_proposal, current_positions, beta)
new_system = pm_top_proposal.new_system
if np.isnan(logp):
raise Exception("NaN in the logp")
integrator = openmm.VerletIntegrator(1*unit.femtoseconds)
platform = openmm.Platform.getPlatformByName("Reference")
context = openmm.Context(new_system, integrator, platform)
context.setPositions(new_positions)
state = context.getState(getEnergy=True)
print(compute_potential_components(context))
potential = state.getPotentialEnergy()
potential_without_units = potential / potential.unit
print(str(potential))
if np.isnan(potential_without_units):
raise Exception("Energy after proposal is NaN")
def test_run_geometry_engine(index=0):
"""
Run the geometry engine a few times to make sure that it actually runs
without exceptions. Convert n-pentane to 2-methylpentane
"""
import logging
logging.basicConfig(level=logging.DEBUG)
import copy
molecule_name_1 = 'benzene'
molecule_name_2 = 'biphenyl'
#molecule_name_1 = 'imatinib'
#molecule_name_2 = 'erlotinib'
molecule1 = generate_initial_molecule(molecule_name_1)
molecule2 = generate_initial_molecule(molecule_name_2)
new_to_old_atom_mapping = align_molecules(molecule1, molecule2)
sys1, pos1, top1 = oemol_to_openmm_system(molecule1, molecule_name_1)
sys2, pos2, top2 = oemol_to_openmm_system(molecule2, molecule_name_2)
import perses.rjmc.geometry as geometry
import perses.rjmc.topology_proposal as topology_proposal
from perses.tests.utils import compute_potential_components
sm_top_proposal = topology_proposal.TopologyProposal(new_topology=top2, new_system=sys2, old_topology=top1, old_system=sys1,
old_chemical_state_key='',new_chemical_state_key='', logp_proposal=0.0, new_to_old_atom_map=new_to_old_atom_mapping, metadata={'test':0.0})
sm_top_proposal._beta = beta
geometry_engine = geometry.FFAllAngleGeometryEngine(metadata={})
# Turn on PDB file writing.
geometry_engine.write_proposal_pdb = True
geometry_engine.pdb_filename_prefix = 't13geometry-proposal'
test_pdb_file = open("%s_to_%s_%d.pdb" % (molecule_name_1, molecule_name_2, index), 'w')
valence_system = copy.deepcopy(sys2)
valence_system.removeForce(3)
valence_system.removeForce(3)
integrator = openmm.VerletIntegrator(1*unit.femtoseconds)
integrator_1 = openmm.VerletIntegrator(1*unit.femtoseconds)
ctx_1 = openmm.Context(sys1, integrator_1)
ctx_1.setPositions(pos1)
ctx_1.setVelocitiesToTemperature(300*unit.kelvin)
integrator_1.step(1000)
pos1_new = ctx_1.getState(getPositions=True).getPositions(asNumpy=True)
context = openmm.Context(sys2, integrator)
context.setPositions(pos2)
state = context.getState(getEnergy=True)
print("Energy before proposal is: %s" % str(state.getPotentialEnergy()))
openmm.LocalEnergyMinimizer.minimize(context)
new_positions, logp_proposal = geometry_engine.propose(sm_top_proposal, pos1_new, beta)
logp_reverse = geometry_engine.logp_reverse(sm_top_proposal, new_positions, pos1, beta)
print(logp_reverse)
app.PDBFile.writeFile(top2, new_positions, file=test_pdb_file)
test_pdb_file.close()
context.setPositions(new_positions)
state2 = context.getState(getEnergy=True)
print("Energy after proposal is: %s" %str(state2.getPotentialEnergy()))
print(compute_potential_components(context))
valence_integrator = openmm.VerletIntegrator(1*unit.femtoseconds)
platform = openmm.Platform.getPlatformByName("Reference")
valence_ctx = openmm.Context(valence_system, valence_integrator, platform)
valence_ctx.setPositions(new_positions)
vstate = valence_ctx.getState(getEnergy=True)
print("Valence energy after proposal is %s " % str(vstate.getPotentialEnergy()))
final_potential = state2.getPotentialEnergy()
return final_potential / final_potential.unit
def test_mutate_from_all_to_all():
"""
Make sure mutations are successful between every possible pair of before-and-after residues
Mutate Ecoli F-ATPase alpha subunit to all 20 amino acids (test going FROM all possibilities)
Mutate each residue to all 19 alternatives
"""
import perses.rjmc.topology_proposal as topology_proposal
import perses.rjmc.geometry as geometry
from perses.tests.utils import compute_potential_components
from openmmtools import testsystems as ts
geometry_engine = geometry.FFAllAngleGeometryEngine()
aminos = ['ALA','ARG','ASN','ASP','CYS','GLN','GLU','GLY','HIS','ILE','LEU','LYS','MET','PHE','PRO','SER','THR','TRP','TYR','VAL']
for aa in aminos:
topology, positions = _get_capped_amino_acid(amino_acid=aa)
modeller = app.Modeller(topology, positions)
ff_filename = "amber99sbildn.xml"
max_point_mutants = 1
ff = app.ForceField(ff_filename)
system = ff.createSystem(modeller.topology)
chain_id = '1'
system_generator = topology_proposal.SystemGenerator([ff_filename])
pm_top_engine = topology_proposal.PointMutationEngine(modeller.topology, system_generator, chain_id, max_point_mutants=max_point_mutants)
current_system = system
current_topology = modeller.topology
current_positions = modeller.positions
minimize_integrator = openmm.VerletIntegrator(1.0*unit.femtosecond)
platform = openmm.Platform.getPlatformByName("Reference")
minimize_context = openmm.Context(current_system, minimize_integrator, platform)
minimize_context.setPositions(current_positions)
initial_state = minimize_context.getState(getEnergy=True)
initial_potential = initial_state.getPotentialEnergy()
openmm.LocalEnergyMinimizer.minimize(minimize_context)
final_state = minimize_context.getState(getEnergy=True, getPositions=True)
final_potential = final_state.getPotentialEnergy()
current_positions = final_state.getPositions()
print("Minimized initial structure from %s to %s" % (str(initial_potential), str(final_potential)))
for k, proposed_amino in enumerate(aminos):
pm_top_engine._allowed_mutations = [[('2',proposed_amino)]]
pm_top_proposal = pm_top_engine.propose(current_system, current_topology)
new_positions, logp = geometry_engine.propose(pm_top_proposal, current_positions, beta)
new_system = pm_top_proposal.new_system
if np.isnan(logp):
raise Exception("NaN in the logp")
integrator = openmm.VerletIntegrator(1*unit.femtoseconds)
platform = openmm.Platform.getPlatformByName("Reference")
context = openmm.Context(new_system, integrator, platform)
context.setPositions(new_positions)
state = context.getState(getEnergy=True)
print(compute_potential_components(context))
potential = state.getPotentialEnergy()
potential_without_units = potential / potential.unit
print(str(potential))
if np.isnan(potential_without_units):
raise Exception("Energy after proposal is NaN")