def test_ring_breaking_detection():
"""
Test the detection of ring-breaking transformations.
"""
from perses.rjmc.topology_proposal import SmallMoleculeSetProposalEngine
from perses.tests.utils import createOEMolFromIUPAC
from perses.tests.utils import render_atom_mapping
molecule1 = createOEMolFromIUPAC("naphthalene")
molecule2 = createOEMolFromIUPAC("benzene")
# Allow ring breaking
new_to_old_atom_map = SmallMoleculeSetProposalEngine._get_mol_atom_map(
molecule1, molecule2, allow_ring_breaking=True)
if not len(new_to_old_atom_map) > 0:
filename = 'mapping-error.png'
render_atom_mapping(filename, molecule1, molecule2,
new_to_old_atom_map)
msg = 'Napthalene -> benzene transformation with allow_ring_breaking=True is not returning a valid mapping\n'
msg += 'Wrote atom mapping to %s for inspection; please check this.' % filename
msg += str(new_to_old_atom_map)
raise Exception(msg)
new_to_old_atom_map = SmallMoleculeSetProposalEngine._get_mol_atom_map(
molecule1, molecule2, allow_ring_breaking=False)
if not len(new_to_old_atom_map) == 0:
filename = 'mapping-error.png'
render_atom_mapping(filename, molecule1, molecule2,
new_to_old_atom_map)
msg = 'Napthalene -> benzene transformation with allow_ring_breaking=False is erroneously allowing ring breaking\n'
msg += 'Wrote atom mapping to %s for inspection; please check this.' % filename
msg += str(new_to_old_atom_map)
raise Exception(msg)
def generate_hybrid_test_topology(mol_name="naphthalene",
ref_mol_name="benzene"):
"""
Generate a test topology proposal and positions for the hybrid test.
"""
from perses.rjmc.topology_proposal import SmallMoleculeSetProposalEngine, TopologyProposal
from perses.tests.utils import createOEMolFromIUPAC, createSystemFromIUPAC
mol = createOEMolFromIUPAC(mol_name)
m, system, positions, topology = createSystemFromIUPAC(mol_name)
refmol = createOEMolFromIUPAC(ref_mol_name)
#map one of the rings
atom_map = SmallMoleculeSetProposalEngine._get_mol_atom_map(mol, refmol)
#now use the mapped atoms to generate a new and old system with identical atoms mapped. This will result in the
#same molecule with the same positions for lambda=0 and 1, and ensures a contiguous atom map
effective_atom_map = {value: value for value in atom_map.values()}
#make a topology proposal with the appropriate data:
top_proposal = TopologyProposal(new_topology=topology,
new_system=system,
old_topology=topology,
old_system=system,
new_to_old_atom_map=effective_atom_map,
new_chemical_state_key="n1",
old_chemical_state_key='n2')
return top_proposal, positions
def generate_vacuum_hybrid_topology(mol_name="naphthalene", ref_mol_name="benzene"):
from topology_proposal import SmallMoleculeSetProposalEngine, TopologyProposal
import simtk.openmm.app as app
from openmoltools import forcefield_generators
from perses.tests.utils import createOEMolFromIUPAC, createSystemFromIUPAC, get_data_filename
m, unsolv_old_system, pos_old, top_old = createSystemFromIUPAC(mol_name)
refmol = createOEMolFromIUPAC(ref_mol_name)
initial_smiles = oechem.OEMolToSmiles(m)
final_smiles = oechem.OEMolToSmiles(refmol)
gaff_xml_filename = get_data_filename("data/gaff.xml")
forcefield = app.ForceField(gaff_xml_filename, 'tip3p.xml')
forcefield.registerTemplateGenerator(forcefield_generators.gaffTemplateGenerator)
solvated_system = forcefield.createSystem(top_old)
gaff_filename = get_data_filename('data/gaff.xml')
system_generator = SystemGenerator([gaff_filename, 'amber99sbildn.xml', 'tip3p.xml'])
geometry_engine = FFAllAngleGeometryEngine()
proposal_engine = SmallMoleculeSetProposalEngine(
[initial_smiles, final_smiles], system_generator, residue_name=mol_name)
#generate topology proposal
topology_proposal = proposal_engine.propose(solvated_system, top_old)
#generate new positions with geometry engine
new_positions, _ = geometry_engine.propose(topology_proposal, pos_old, beta)
return topology_proposal, pos_old, new_positions
def generate_vacuum_hybrid_topology(mol_name="naphthalene", ref_mol_name="benzene"):
from topology_proposal import SmallMoleculeSetProposalEngine, TopologyProposal
import simtk.openmm.app as app
from openmoltools import forcefield_generators
from perses.tests.utils import createOEMolFromIUPAC, createSystemFromIUPAC, get_data_filename
m, unsolv_old_system, pos_old, top_old = createSystemFromIUPAC(mol_name)
refmol = createOEMolFromIUPAC(ref_mol_name)
initial_smiles = oechem.OEMolToSmiles(m)
final_smiles = oechem.OEMolToSmiles(refmol)
gaff_xml_filename = get_data_filename("data/gaff.xml")
forcefield = app.ForceField(gaff_xml_filename, 'tip3p.xml')
forcefield.registerTemplateGenerator(forcefield_generators.gaffTemplateGenerator)
solvated_system = forcefield.createSystem(top_old)
gaff_filename = get_data_filename('data/gaff.xml')
system_generator = SystemGenerator([gaff_filename, 'amber99sbildn.xml', 'tip3p.xml'])
geometry_engine = FFAllAngleGeometryEngine()
proposal_engine = SmallMoleculeSetProposalEngine(
[initial_smiles, final_smiles], system_generator, residue_name=mol_name)
#generate topology proposal
topology_proposal = proposal_engine.propose(solvated_system, top_old)
#generate new positions with geometry engine
new_positions, _ = geometry_engine.propose(topology_proposal, pos_old, beta)
return topology_proposal, pos_old, new_positions
def generate_solvated_hybrid_test_topology(current_mol_name="naphthalene", proposed_mol_name="benzene"):
"""
Generate a test solvated topology proposal, current positions, and new positions triplet
from two IUPAC molecule names.
Parameters
----------
current_mol_name : str, optional
name of the first molecule
proposed_mol_name : str, optional
name of the second molecule
Returns
-------
topology_proposal : perses.rjmc.topology_proposal
The topology proposal representing the transformation
current_positions : np.array, unit-bearing
The positions of the initial system
new_positions : np.array, unit-bearing
The positions of the new system
"""
import simtk.openmm.app as app
from openmoltools import forcefield_generators
from perses.tests.utils import createOEMolFromIUPAC, createSystemFromIUPAC, get_data_filename
current_mol, unsolv_old_system, pos_old, top_old = createSystemFromIUPAC(current_mol_name)
proposed_mol = createOEMolFromIUPAC(proposed_mol_name)
initial_smiles = oechem.OEMolToSmiles(current_mol)
final_smiles = oechem.OEMolToSmiles(proposed_mol)
gaff_xml_filename = get_data_filename("data/gaff.xml")
forcefield = app.ForceField(gaff_xml_filename, 'tip3p.xml')
forcefield.registerTemplateGenerator(forcefield_generators.gaffTemplateGenerator)
modeller = app.Modeller(top_old, pos_old)
modeller.addSolvent(forcefield, model='tip3p', padding=9.0*unit.angstrom)
solvated_topology = modeller.getTopology()
solvated_positions = modeller.getPositions()
solvated_system = forcefield.createSystem(solvated_topology, nonbondedMethod=app.PME, removeCMMotion=False)
barostat = openmm.MonteCarloBarostat(1.0*unit.atmosphere, temperature, 50)
solvated_system.addForce(barostat)
gaff_filename = get_data_filename('data/gaff.xml')
system_generator = SystemGenerator([gaff_filename, 'amber99sbildn.xml', 'tip3p.xml'], barostat=barostat, forcefield_kwargs={'removeCMMotion': False, 'nonbondedMethod': app.PME})
geometry_engine = geometry.FFAllAngleGeometryEngine()
proposal_engine = SmallMoleculeSetProposalEngine(
[initial_smiles, final_smiles], system_generator, residue_name=current_mol_name)
#generate topology proposal
topology_proposal = proposal_engine.propose(solvated_system, solvated_topology)
#generate new positions with geometry engine
new_positions, _ = geometry_engine.propose(topology_proposal, solvated_positions, beta)
return topology_proposal, solvated_positions, new_positions
def generate_solvated_hybrid_test_topology(current_mol_name="naphthalene", proposed_mol_name="benzene"):
"""
Generate a test solvated topology proposal, current positions, and new positions triplet
from two IUPAC molecule names.
Parameters
----------
current_mol_name : str, optional
name of the first molecule
proposed_mol_name : str, optional
name of the second molecule
Returns
-------
topology_proposal : perses.rjmc.topology_proposal
The topology proposal representing the transformation
current_positions : np.array, unit-bearing
The positions of the initial system
new_positions : np.array, unit-bearing
The positions of the new system
"""
import simtk.openmm.app as app
from openmoltools import forcefield_generators
from perses.tests.utils import createOEMolFromIUPAC, createSystemFromIUPAC, get_data_filename
current_mol, unsolv_old_system, pos_old, top_old = createSystemFromIUPAC(current_mol_name)
proposed_mol = createOEMolFromIUPAC(proposed_mol_name)
initial_smiles = oechem.OEMolToSmiles(current_mol)
final_smiles = oechem.OEMolToSmiles(proposed_mol)
gaff_xml_filename = get_data_filename("data/gaff.xml")
forcefield = app.ForceField(gaff_xml_filename, 'tip3p.xml')
forcefield.registerTemplateGenerator(forcefield_generators.gaffTemplateGenerator)
modeller = app.Modeller(top_old, pos_old)
modeller.addSolvent(forcefield, model='tip3p', padding=9.0*unit.angstrom)
solvated_topology = modeller.getTopology()
solvated_positions = modeller.getPositions()
solvated_system = forcefield.createSystem(solvated_topology, nonbondedMethod=app.PME, removeCMMotion=False)
barostat = openmm.MonteCarloBarostat(1.0*unit.atmosphere, temperature, 50)
solvated_system.addForce(barostat)
gaff_filename = get_data_filename('data/gaff.xml')
system_generator = SystemGenerator([gaff_filename, 'amber99sbildn.xml', 'tip3p.xml'], barostat=barostat, forcefield_kwargs={'removeCMMotion': False, 'nonbondedMethod': app.PME})
geometry_engine = geometry.FFAllAngleGeometryEngine()
proposal_engine = SmallMoleculeSetProposalEngine(
[initial_smiles, final_smiles], system_generator, residue_name=current_mol_name)
#generate topology proposal
topology_proposal = proposal_engine.propose(solvated_system, solvated_topology)
#generate new positions with geometry engine
new_positions, _ = geometry_engine.propose(topology_proposal, solvated_positions, beta)
return topology_proposal, solvated_positions, new_positions
def generate_solvated_hybrid_test_topology(mol_name="naphthalene",
ref_mol_name="benzene"):
from perses.rjmc.topology_proposal import SmallMoleculeSetProposalEngine, TopologyProposal
import simtk.openmm.app as app
from openmoltools import forcefield_generators
from perses.tests.utils import createOEMolFromIUPAC, createSystemFromIUPAC, get_data_filename
mol = createOEMolFromIUPAC(mol_name)
m, unsolv_system, pos, top = createSystemFromIUPAC(mol_name)
refmol = createOEMolFromIUPAC(ref_mol_name)
gaff_xml_filename = get_data_filename("data/gaff.xml")
forcefield = app.ForceField(gaff_xml_filename, 'tip3p.xml')
forcefield.registerTemplateGenerator(
forcefield_generators.gaffTemplateGenerator)
#map one of the rings
atom_map = SmallMoleculeSetProposalEngine._get_mol_atom_map(mol, refmol)
#now use the mapped atoms to generate a new and old system with identical atoms mapped. This will result in the
#same molecule with the same positions for lambda=0 and 1, and ensures a contiguous atom map
effective_atom_map = {value: value for value in atom_map.values()}
modeller = app.Modeller(top, pos)
modeller.addSolvent(forcefield, model='tip3p', padding=9.0 * unit.angstrom)
topology = modeller.getTopology()
positions = modeller.getPositions()
system = forcefield.createSystem(topology, nonbondedMethod=app.PME)
n_atoms_old_system = unsolv_system.getNumParticles()
n_atoms_after_solvation = system.getNumParticles()
for i in range(n_atoms_old_system, n_atoms_after_solvation):
effective_atom_map[i] = i
top_proposal = TopologyProposal(new_topology=topology,
new_system=system,
old_topology=topology,
old_system=system,
new_to_old_atom_map=effective_atom_map,
new_chemical_state_key="n1",
old_chemical_state_key='n2')
return top_proposal, positions
def createSystemFromIUPAC(iupac_name):
"""
Create an openmm system out of an oemol
Parameters
----------
iupac_name : str
IUPAC name
Returns
-------
molecule : openeye.OEMol
OEMol molecule
system : openmm.System object
OpenMM system
positions : [n,3] np.array of floats
Positions
topology : openmm.app.Topology object
Topology
"""
# Create OEMol
molecule = createOEMolFromIUPAC(iupac_name)
# Generate a topology.
from openmoltools.forcefield_generators import generateTopologyFromOEMol
topology = generateTopologyFromOEMol(molecule)
# Initialize a forcefield with GAFF.
# TODO: Fix path for `gaff.xml` since it is not yet distributed with OpenMM
from simtk.openmm.app import ForceField
gaff_xml_filename = get_data_filename('data/gaff.xml')
forcefield = ForceField(gaff_xml_filename)
# Generate template and parameters.
from openmoltools.forcefield_generators import generateResidueTemplate
[template, ffxml] = generateResidueTemplate(molecule)
# Register the template.
forcefield.registerResidueTemplate(template)
# Add the parameters.
forcefield.loadFile(StringIO(ffxml))
# Create the system.
system = forcefield.createSystem(topology, removeCMMotion=False)
# Extract positions
positions = extractPositionsFromOEMOL(molecule)
return (molecule, system, positions, topology)
def createSystemFromIUPAC(iupac_name):
"""
Create an openmm system out of an oemol
Parameters
----------
iupac_name : str
IUPAC name
Returns
-------
molecule : openeye.OEMol
OEMol molecule
system : openmm.System object
OpenMM system
positions : [n,3] np.array of floats
Positions
topology : openmm.app.Topology object
Topology
"""
# Create OEMol
molecule = createOEMolFromIUPAC(iupac_name)
# Generate a topology.
from openmoltools.forcefield_generators import generateTopologyFromOEMol
topology = generateTopologyFromOEMol(molecule)
# Initialize a forcefield with GAFF.
# TODO: Fix path for `gaff.xml` since it is not yet distributed with OpenMM
from simtk.openmm.app import ForceField
gaff_xml_filename = get_data_filename('data/gaff.xml')
forcefield = ForceField(gaff_xml_filename)
# Generate template and parameters.
from openmoltools.forcefield_generators import generateResidueTemplate
[template, ffxml] = generateResidueTemplate(molecule)
# Register the template.
forcefield.registerResidueTemplate(template)
# Add the parameters.
forcefield.loadFile(StringIO(ffxml))
# Create the system.
system = forcefield.createSystem(topology, removeCMMotion=False)
# Extract positions
positions = extractPositionsFromOEMOL(molecule)
return (molecule, system, positions, topology)
def generate_solvated_hybrid_test_topology(mol_name="naphthalene", ref_mol_name="benzene"):
from perses.rjmc.topology_proposal import SmallMoleculeSetProposalEngine, TopologyProposal
import simtk.openmm.app as app
from openmoltools import forcefield_generators
from perses.tests.utils import createOEMolFromIUPAC, createSystemFromIUPAC, get_data_filename
mol = createOEMolFromIUPAC(mol_name)
m, unsolv_system, pos, top = createSystemFromIUPAC(mol_name)
refmol = createOEMolFromIUPAC(ref_mol_name)
gaff_xml_filename = get_data_filename("data/gaff.xml")
forcefield = app.ForceField(gaff_xml_filename, 'tip3p.xml')
forcefield.registerTemplateGenerator(forcefield_generators.gaffTemplateGenerator)
#map one of the rings
atom_map = SmallMoleculeSetProposalEngine._get_mol_atom_map(mol, refmol)
#now use the mapped atoms to generate a new and old system with identical atoms mapped. This will result in the
#same molecule with the same positions for lambda=0 and 1, and ensures a contiguous atom map
effective_atom_map = {value : value for value in atom_map.values()}
modeller = app.Modeller(top, pos)
modeller.addSolvent(forcefield, model='tip3p', padding=9.0*unit.angstrom)
topology = modeller.getTopology()
positions = modeller.getPositions()
system = forcefield.createSystem(topology, nonbondedMethod=app.PME)
n_atoms_old_system = unsolv_system.getNumParticles()
n_atoms_after_solvation = system.getNumParticles()
for i in range(n_atoms_old_system, n_atoms_after_solvation):
effective_atom_map[i] = i
top_proposal = TopologyProposal(new_topology=topology, new_system=system, old_topology=topology, old_system=system, new_to_old_atom_map=effective_atom_map, new_chemical_state_key="n1", old_chemical_state_key='n2')
return top_proposal, positions
def generate_vacuum_topology_proposal(current_mol_name="benzene", proposed_mol_name="toluene"):
"""
Generate a test vacuum topology proposal, current positions, and new positions triplet
from two IUPAC molecule names.
Parameters
----------
current_mol_name : str, optional
name of the first molecule
proposed_mol_name : str, optional
name of the second molecule
Returns
-------
topology_proposal : perses.rjmc.topology_proposal
The topology proposal representing the transformation
current_positions : np.array, unit-bearing
The positions of the initial system
new_positions : np.array, unit-bearing
The positions of the new system
"""
from openmoltools import forcefield_generators
from perses.tests.utils import createOEMolFromIUPAC, createSystemFromIUPAC, get_data_filename
current_mol, unsolv_old_system, pos_old, top_old = createSystemFromIUPAC(current_mol_name)
proposed_mol = createOEMolFromIUPAC(proposed_mol_name)
initial_smiles = oechem.OEMolToSmiles(current_mol)
final_smiles = oechem.OEMolToSmiles(proposed_mol)
gaff_xml_filename = get_data_filename("data/gaff.xml")
forcefield = app.ForceField(gaff_xml_filename, 'tip3p.xml')
forcefield.registerTemplateGenerator(forcefield_generators.gaffTemplateGenerator)
solvated_system = forcefield.createSystem(top_old, removeCMMotion=False)
gaff_filename = get_data_filename('data/gaff.xml')
system_generator = SystemGenerator([gaff_filename, 'amber99sbildn.xml', 'tip3p.xml'], forcefield_kwargs={'removeCMMotion': False, 'nonbondedMethod': app.NoCutoff})
geometry_engine = geometry.FFAllAngleGeometryEngine()
proposal_engine = SmallMoleculeSetProposalEngine(
[initial_smiles, final_smiles], system_generator, residue_name=current_mol_name)
#generate topology proposal
topology_proposal = proposal_engine.propose(solvated_system, top_old, current_mol=current_mol, proposed_mol=proposed_mol)
#generate new positions with geometry engine
new_positions, _ = geometry_engine.propose(topology_proposal, pos_old, beta)
return topology_proposal, pos_old, new_positions
def generate_hybrid_test_topology(mol_name="naphthalene", ref_mol_name="benzene"):
"""
Generate a test topology proposal and positions for the hybrid test.
"""
from perses.rjmc.topology_proposal import SmallMoleculeSetProposalEngine, TopologyProposal
from perses.tests.utils import createOEMolFromIUPAC, createSystemFromIUPAC
mol = createOEMolFromIUPAC(mol_name)
m, system, positions, topology = createSystemFromIUPAC(mol_name)
refmol = createOEMolFromIUPAC(ref_mol_name)
#map one of the rings
atom_map = SmallMoleculeSetProposalEngine._get_mol_atom_map(mol, refmol)
#now use the mapped atoms to generate a new and old system with identical atoms mapped. This will result in the
#same molecule with the same positions for lambda=0 and 1, and ensures a contiguous atom map
effective_atom_map = {value : value for value in atom_map.values()}
#make a topology proposal with the appropriate data:
top_proposal = TopologyProposal(new_topology=topology, new_system=system, old_topology=topology, old_system=system, new_to_old_atom_map=effective_atom_map, new_chemical_state_key="n1", old_chemical_state_key='n2')
return top_proposal, positions
def compare_energies(mol_name="naphthalene", ref_mol_name="benzene"):
"""
Make an atom map where the molecule at either lambda endpoint is identical, and check that the energies are also the same.
"""
from perses.rjmc.topology_proposal import SmallMoleculeSetProposalEngine, TopologyProposal
from perses.annihilation.new_relative import HybridTopologyFactory
import simtk.openmm as openmm
from perses.tests.utils import createOEMolFromIUPAC, createSystemFromIUPAC
mol_name = "naphthalene"
ref_mol_name = "benzene"
mol = createOEMolFromIUPAC(mol_name)
m, system, positions, topology = createSystemFromIUPAC(mol_name)
refmol = createOEMolFromIUPAC(ref_mol_name)
#map one of the rings
atom_map = SmallMoleculeSetProposalEngine._get_mol_atom_map(mol, refmol)
#now use the mapped atoms to generate a new and old system with identical atoms mapped. This will result in the
#same molecule with the same positions for lambda=0 and 1, and ensures a contiguous atom map
effective_atom_map = {value: value for value in atom_map.values()}
#make a topology proposal with the appropriate data:
top_proposal = TopologyProposal(new_topology=topology,
new_system=system,
old_topology=topology,
old_system=system,
new_to_old_atom_map=effective_atom_map,
new_chemical_state_key="n1",
old_chemical_state_key='n2')
factory = HybridTopologyFactory(top_proposal, positions, positions)
alchemical_system = factory.hybrid_system
alchemical_positions = factory.hybrid_positions
integrator = openmm.VerletIntegrator(1)
platform = openmm.Platform.getPlatformByName("Reference")
context = openmm.Context(alchemical_system, integrator, platform)
context.setPositions(alchemical_positions)
functions = {
'lambda_sterics':
'2*lambda * step(0.5 - lambda) + (1.0 - step(0.5 - lambda))',
'lambda_electrostatics': '2*(lambda - 0.5) * step(lambda - 0.5)',
'lambda_bonds': 'lambda',
'lambda_angles': 'lambda',
'lambda_torsions': 'lambda'
}
#set all to zero
for parm in functions.keys():
context.setParameter(parm, 0.0)
initial_energy = context.getState(getEnergy=True).getPotentialEnergy()
#set all to one
for parm in functions.keys():
context.setParameter(parm, 1.0)
final_energy = context.getState(getEnergy=True).getPotentialEnergy()
if np.abs(final_energy -
initial_energy) > 1.0e-6 * unit.kilojoule_per_mole:
raise Exception(
"The energy at the endpoints was not equal for molecule %s" %
mol_name)
def generate_vacuum_topology_proposal(current_mol_name="benzene", proposed_mol_name="toluene", forcefield_kwargs=None, system_generator_kwargs=None):
"""
Generate a test vacuum topology proposal, current positions, and new positions triplet from two IUPAC molecule names.
Constraints are added to the system by default. To override this, set ``forcefield_kwargs = None``.
Parameters
----------
current_mol_name : str, optional
name of the first molecule
proposed_mol_name : str, optional
name of the second molecule
forcefield_kwargs : dict, optional, default=None
Additional arguments to ForceField in addition to
'removeCMMotion': False, 'nonbondedMethod': app.NoCutoff
system_generator_kwargs : dict, optional, default=None
Dict passed onto SystemGenerator
Returns
-------
topology_proposal : perses.rjmc.topology_proposal
The topology proposal representing the transformation
current_positions : np.array, unit-bearing
The positions of the initial system
new_positions : np.array, unit-bearing
The positions of the new system
"""
from openmoltools import forcefield_generators
from perses.tests.utils import createOEMolFromIUPAC, createSystemFromIUPAC, get_data_filename
gaff_filename = get_data_filename('data/gaff.xml')
default_forcefield_kwargs = {'removeCMMotion': False, 'nonbondedMethod': app.NoCutoff, 'constraints' : app.HBonds}
forcefield_kwargs = default_forcefield_kwargs.update(forcefield_kwargs) if (forcefield_kwargs is not None) else default_forcefield_kwargs
system_generator_kwargs = system_generator_kwargs if (system_generator_kwargs is not None) else dict()
system_generator = SystemGenerator([gaff_filename, 'amber99sbildn.xml', 'tip3p.xml'],
forcefield_kwargs=forcefield_kwargs,
**system_generator_kwargs)
old_oemol = createOEMolFromIUPAC(current_mol_name)
from openmoltools.forcefield_generators import generateTopologyFromOEMol
old_topology = generateTopologyFromOEMol(old_oemol)
old_positions = extractPositionsFromOEMOL(old_oemol)
old_smiles = oechem.OEMolToSmiles(old_oemol)
old_system = system_generator.build_system(old_topology)
new_oemol = createOEMolFromIUPAC(proposed_mol_name)
new_smiles = oechem.OEMolToSmiles(new_oemol)
geometry_engine = geometry.FFAllAngleGeometryEngine()
proposal_engine = SmallMoleculeSetProposalEngine(
[old_smiles, new_smiles], system_generator, residue_name=current_mol_name)
#generate topology proposal
topology_proposal = proposal_engine.propose(old_system, old_topology, current_mol=old_oemol, proposed_mol=new_oemol)
# show atom mapping
filename = str(current_mol_name)+str(proposed_mol_name)+'.pdf'
render_atom_mapping(filename, old_oemol, new_oemol, topology_proposal.new_to_old_atom_map)
#generate new positions with geometry engine
new_positions, _ = geometry_engine.propose(topology_proposal, old_positions, beta)
# DEBUG: Zero out bonds and angles for one system
#print('Zeroing bonds of old system')
#for force in topology_proposal.old_system.getForces():
# if force.__class__.__name__ == 'HarmonicAngleForce':
# for index in range(force.getNumAngles()):
# p1, p2, p3, angle, K = force.getAngleParameters(index)
# K *= 0.0
# force.setAngleParameters(index, p1, p2, p3, angle, K)
# if False and force.__class__.__name__ == 'HarmonicBondForce':
# for index in range(force.getNumBonds()):
# p1, p2, r0, K = force.getBondParameters(index)
# K *= 0.0
# force.setBondParameters(index, p1, p2, r0, K)
# DEBUG : Box vectors
#box_vectors = np.eye(3) * 100 * unit.nanometers
#topology_proposal.old_system.setDefaultPeriodicBoxVectors(box_vectors[0,:], box_vectors[1,:], box_vectors[2,:])
#topology_proposal.new_system.setDefaultPeriodicBoxVectors(box_vectors[0,:], box_vectors[1,:], box_vectors[2,:])
return topology_proposal, old_positions, new_positions
def test_logp_forward_check_for_vacuum_topology_proposal(current_mol_name = 'propane', proposed_mol_name = 'octane', num_iterations = 100, neglect_angles = True):
"""
Generate a test vacuum topology proposal, current positions, and new positions triplet
from two IUPAC molecule names. Assert that the logp_forward < 1e3.
This assertion will fail if the proposal order tool proposed the placement of the a carbon before a previously defined carbon in the alkane.
Parameters
----------
current_mol_name : str, optional
name of the first molecule
proposed_mol_name : str, optional
name of the second molecule
Returns
-------
topology_proposal : perses.rjmc.topology_proposal
The topology proposal representing the transformation
current_positions : np.array, unit-bearing
The positions of the initial system
new_positions : np.array, unit-bearing
The positions of the new system
"""
from openmoltools import forcefield_generators
from perses.tests.utils import createOEMolFromIUPAC, createSystemFromIUPAC, get_data_filename
current_mol, unsolv_old_system, pos_old, top_old = createSystemFromIUPAC(current_mol_name)
proposed_mol = createOEMolFromIUPAC(proposed_mol_name)
initial_smiles = oechem.OEMolToSmiles(current_mol)
final_smiles = oechem.OEMolToSmiles(proposed_mol)
gaff_xml_filename = get_data_filename("data/gaff.xml")
forcefield = app.ForceField(gaff_xml_filename, 'tip3p.xml')
forcefield.registerTemplateGenerator(forcefield_generators.gaffTemplateGenerator)
solvated_system = forcefield.createSystem(top_old, removeCMMotion=False)
gaff_filename = get_data_filename('data/gaff.xml')
system_generator = SystemGenerator([gaff_filename, 'amber99sbildn.xml', 'tip3p.xml'], forcefield_kwargs={'removeCMMotion': False, 'nonbondedMethod': app.NoCutoff})
geometry_engine = geometry.FFAllAngleGeometryEngine(n_bond_divisions=100, n_angle_divisions=180, n_torsion_divisions=360, neglect_angles = neglect_angles)
proposal_engine = SmallMoleculeSetProposalEngine(
[initial_smiles, final_smiles], system_generator, residue_name=current_mol_name)
#generate topology proposal
topology_proposal = proposal_engine.propose(solvated_system, top_old, current_mol=current_mol, proposed_mol=proposed_mol)
# show atom mapping
filename = str(current_mol_name)+str(proposed_mol_name)+'.pdf'
render_atom_mapping(filename,current_mol,proposed_mol,topology_proposal.new_to_old_atom_map)
total_works = []
for _ in range(num_iterations):
#generate new positions with geometry engine
new_positions, logp_forward = geometry_engine.propose(topology_proposal, pos_old, beta)
logp_reverse = geometry_engine.logp_reverse(topology_proposal, new_positions, pos_old, beta)
#now just render forward and backward work
work_fwd = logp_forward + geometry_engine.forward_final_context_reduced_potential - geometry_engine.forward_atoms_with_positions_reduced_potential
work_bkwd = logp_reverse + geometry_engine.reverse_atoms_with_positions_reduced_potential - geometry_engine.reverse_final_context_reduced_potential
total_work = logp_forward - logp_reverse + geometry_engine.forward_final_context_reduced_potential - geometry_engine.reverse_final_context_reduced_potential
total_works.append(total_work)
print("forward, backward works : {}, {}".format(work_fwd, work_bkwd))
print("total_work: {}".format(total_work))
assert abs(work_fwd - work_bkwd - total_work) < 1, "The difference of fwd and backward works is not equal to the total work (within 1kT)"
assert logp_forward < 1e3, "A heavy atom was proposed in an improper order"
def compare_energies(mol_name="naphthalene", ref_mol_name="benzene"):
"""
Make an atom map where the molecule at either lambda endpoint is identical, and check that the energies are also the same.
"""
from perses.rjmc.topology_proposal import SmallMoleculeSetProposalEngine, TopologyProposal
from perses.annihilation.new_relative import HybridTopologyFactory
import simtk.openmm as openmm
from perses.tests.utils import createOEMolFromIUPAC, createSystemFromIUPAC
mol_name = "naphthalene"
ref_mol_name = "benzene"
mol = createOEMolFromIUPAC(mol_name)
m, system, positions, topology = createSystemFromIUPAC(mol_name)
refmol = createOEMolFromIUPAC(ref_mol_name)
#map one of the rings
atom_map = SmallMoleculeSetProposalEngine._get_mol_atom_map(mol, refmol)
#now use the mapped atoms to generate a new and old system with identical atoms mapped. This will result in the
#same molecule with the same positions for lambda=0 and 1, and ensures a contiguous atom map
effective_atom_map = {value : value for value in atom_map.values()}
#make a topology proposal with the appropriate data:
top_proposal = TopologyProposal(new_topology=topology, new_system=system, old_topology=topology, old_system=system, new_to_old_atom_map=effective_atom_map, new_chemical_state_key="n1", old_chemical_state_key='n2')
factory = HybridTopologyFactory(top_proposal, positions, positions)
alchemical_system = factory.hybrid_system
alchemical_positions = factory.hybrid_positions
integrator = openmm.VerletIntegrator(1)
platform = openmm.Platform.getPlatformByName("Reference")
context = openmm.Context(alchemical_system, integrator, platform)
context.setPositions(alchemical_positions)
functions = {
'lambda_sterics' : '2*lambda * step(0.5 - lambda) + (1.0 - step(0.5 - lambda))',
'lambda_electrostatics' : '2*(lambda - 0.5) * step(lambda - 0.5)',
'lambda_bonds' : 'lambda',
'lambda_angles' : 'lambda',
'lambda_torsions' : 'lambda'
}
#set all to zero
for parm in functions.keys():
context.setParameter(parm, 0.0)
initial_energy = context.getState(getEnergy=True).getPotentialEnergy()
#set all to one
for parm in functions.keys():
context.setParameter(parm, 1.0)
final_energy = context.getState(getEnergy=True).getPotentialEnergy()
if np.abs(final_energy - initial_energy) > 1.0e-6*unit.kilojoule_per_mole:
raise Exception("The energy at the endpoints was not equal for molecule %s" % mol_name)