def test_parameterize(self):
"""Test parameterizing molecules with template generator for all supported force fields"""
# Test all supported small molecule force fields
for small_molecule_forcefield in self.TEMPLATE_GENERATOR.INSTALLED_FORCEFIELDS:
print(f'Testing {small_molecule_forcefield}')
# Create a generator that knows about a few molecules
# TODO: Should the generator also load the appropriate force field files into the ForceField object?
generator = self.TEMPLATE_GENERATOR(molecules=self.molecules, forcefield=small_molecule_forcefield)
# Check that we have loaded the right force field
assert generator.forcefield == small_molecule_forcefield
# Create a ForceField with the appropriate small molecule force field
from simtk.openmm.app import ForceField
forcefield = ForceField()
# Register the template generator
forcefield.registerTemplateGenerator(generator.generator)
# Parameterize some molecules
from simtk.openmm.app import NoCutoff
from openmmforcefields.utils import Timer
for molecule in self.molecules:
openmm_topology = molecule.to_topology().to_openmm()
with Timer() as t1:
system = forcefield.createSystem(openmm_topology, nonbondedMethod=NoCutoff)
assert system.getNumParticles() == molecule.n_atoms
# Molecule should now be cached
with Timer() as t2:
system = forcefield.createSystem(openmm_topology, nonbondedMethod=NoCutoff)
assert system.getNumParticles() == molecule.n_atoms
assert (t2.interval() < t1.interval())
def test_debug_ffxml(self):
"""Test that debug ffxml file is created when requested"""
with tempfile.TemporaryDirectory() as tmpdirname:
debug_ffxml_filename = os.path.join(tmpdirname, 'molecule.ffxml')
cache = os.path.join(tmpdirname, 'db.json')
# Create a generator that only knows about one molecule
molecule = self.molecules[0]
generator = self.TEMPLATE_GENERATOR(molecules=molecule, cache=cache)
# Create a ForceField
from simtk.openmm.app import ForceField
forcefield = ForceField()
# Register the template generator
forcefield.registerTemplateGenerator(generator.generator)
# Ensure no file is created
from simtk.openmm.app import NoCutoff
openmm_topology = molecule.to_topology().to_openmm()
system = forcefield.createSystem(openmm_topology, nonbondedMethod=NoCutoff)
assert not os.path.exists(debug_ffxml_filename)
# Enable debug file output creation
forcefield = ForceField()
forcefield.registerTemplateGenerator(generator.generator)
generator.debug_ffxml_filename = debug_ffxml_filename
# Ensure that an ffxml file is created
system = forcefield.createSystem(openmm_topology, nonbondedMethod=NoCutoff)
assert os.path.exists(debug_ffxml_filename)
# Ensure we can use that file to create a new force field
forcefield_from_ffxml = ForceField()
if hasattr(generator, 'gaff_xml_filename'):
forcefield_from_ffxml.loadFile(generator.gaff_xml_filename)
forcefield_from_ffxml.loadFile(debug_ffxml_filename)
system2 = forcefield_from_ffxml.createSystem(openmm_topology, nonbondedMethod=NoCutoff)
# TODO: Test that systems are equivalent
assert system.getNumParticles() == system2.getNumParticles()
def test_add_solvent(self):
"""Test using simtk.opnmm.app.Modeller to add solvent to a small molecule parameterized by template generator"""
# Select a molecule to add solvent around
from simtk.openmm.app import NoCutoff, Modeller
from simtk import unit
molecule = self.molecules[0]
openmm_topology = molecule.to_topology().to_openmm()
openmm_positions = molecule.conformers[0]
# Try adding solvent without residue template generator; this will fail
from simtk.openmm.app import ForceField
forcefield = ForceField('tip3p.xml')
# Add solvent to a system containing a small molecule
modeller = Modeller(openmm_topology, openmm_positions)
try:
modeller.addSolvent(forcefield, model='tip3p', padding=6.0*unit.angstroms)
except ValueError as e:
pass
# Create a generator that knows about a few molecules
generator = self.TEMPLATE_GENERATOR(molecules=self.molecules)
# Add to the forcefield object
forcefield.registerTemplateGenerator(generator.generator)
# Add solvent to a system containing a small molecule
# This should succeed
modeller.addSolvent(forcefield, model='tip3p', padding=6.0*unit.angstroms)
def test_charge(self):
"""Test that charges are nonzero after charging if the molecule does not contain user charges"""
# Create a generator that does not know about any molecules
generator = self.TEMPLATE_GENERATOR()
# Create a ForceField
from simtk.openmm.app import ForceField
forcefield = ForceField()
# Register the template generator
forcefield.registerTemplateGenerator(generator.generator)
# Check that parameterizing a molecule using user-provided charges produces expected charges
import numpy as np
from simtk import unit
molecule = self.molecules[0]
# Ensure partial charges are initially zero
assert np.all(molecule.partial_charges / unit.elementary_charge == 0)
# Add the molecule
generator.add_molecules(molecule)
# Create the System
from simtk.openmm.app import NoCutoff
openmm_topology = molecule.to_topology().to_openmm()
system = forcefield.createSystem(openmm_topology,
nonbondedMethod=NoCutoff)
# Ensure charges are no longer zero
assert not np.all(
self.charges_from_system(system) ==
0), "System has zero charges despite molecule not being charged"
def test_charge_from_molecules(self):
"""Test that user-specified partial charges are used if requested"""
# Create a generator that does not know about any molecules
generator = self.TEMPLATE_GENERATOR()
# Create a ForceField
from simtk.openmm.app import ForceField
forcefield = ForceField()
# Register the template generator
forcefield.registerTemplateGenerator(generator.generator)
# Check that parameterizing a molecule using user-provided charges produces expected charges
import numpy as np
from simtk import unit
molecule = self.molecules[0]
charges = np.random.random([molecule.n_particles])
charges += (molecule.total_charge - charges.sum()) / molecule.n_particles
molecule.partial_charges = unit.Quantity(charges, unit.elementary_charge)
assert not np.all(molecule.partial_charges / unit.elementary_charge == 0)
# Add the molecule
generator.add_molecules(molecule)
# Create the System
from simtk.openmm.app import NoCutoff
openmm_topology = molecule.to_topology().to_openmm()
system = forcefield.createSystem(openmm_topology, nonbondedMethod=NoCutoff)
assert self.charges_are_equal(system, molecule)
def imatinib_timing():
print("Loading imatinib...")
# Load the PDB file.
from simtk.openmm.app import PDBFile
pdb_filename = utils.get_data_filename("chemicals/imatinib/imatinib.pdb")
pdb = PDBFile(pdb_filename)
# Create a ForceField object.
gaff_xml_filename = utils.get_data_filename("parameters/gaff.xml")
forcefield = ForceField(gaff_xml_filename)
# Add the residue template generator.
from openmoltools.forcefield_generators import gaffTemplateGenerator
forcefield.registerTemplateGenerator(gaffTemplateGenerator)
# Parameterize system.
system = forcefield.createSystem(pdb.topology, nonbondedMethod=NoCutoff)
integrator = openmm.LangevinIntegrator(300 * unit.kelvin, 5.0 / unit.picoseconds, 1.0 * unit.femtoseconds)
# Create Context
context = openmm.Context(system, integrator)
context.setPositions(pdb.positions)
integrator.step(100)
import time
nsteps = 10000000
initial_time = time.time()
integrator.step(nsteps)
state = context.getState().getPeriodicBoxVectors() # force dynamics
final_time = time.time()
elapsed_time = final_time / initial_time
time_per_step = elapsed_time / float(nsteps)
print('time per force evaluation is %.3f us' % (time_per_step*1e6))
def imatinib_timing():
print("Loading imatinib...")
# Load the PDB file.
from simtk.openmm.app import PDBFile
pdb_filename = utils.get_data_filename("chemicals/imatinib/imatinib.pdb")
pdb = PDBFile(pdb_filename)
# Create a ForceField object.
gaff_xml_filename = utils.get_data_filename("parameters/gaff.xml")
forcefield = ForceField(gaff_xml_filename)
# Add the residue template generator.
from openmoltools.forcefield_generators import gaffTemplateGenerator
forcefield.registerTemplateGenerator(gaffTemplateGenerator)
# Parameterize system.
system = forcefield.createSystem(pdb.topology, nonbondedMethod=NoCutoff)
integrator = openmm.LangevinIntegrator(300 * unit.kelvin,
5.0 / unit.picoseconds,
1.0 * unit.femtoseconds)
# Create Context
context = openmm.Context(system, integrator)
context.setPositions(pdb.positions)
integrator.step(100)
import time
nsteps = 10000000
initial_time = time.time()
integrator.step(nsteps)
state = context.getState().getPeriodicBoxVectors() # force dynamics
final_time = time.time()
elapsed_time = final_time / initial_time
time_per_step = elapsed_time / float(nsteps)
print('time per force evaluation is %.3f us' % (time_per_step * 1e6))
def test_cache(self):
"""Test template generator cache capability"""
from simtk.openmm.app import ForceField, NoCutoff
with tempfile.TemporaryDirectory() as tmpdirname:
# Create a generator that also has a database cache
cache = os.path.join(tmpdirname, 'db.json')
generator = self.TEMPLATE_GENERATOR(molecules=self.molecules,
cache=cache)
# Create a ForceField
forcefield = ForceField()
# Register the template generator
forcefield.registerTemplateGenerator(generator.generator)
# Parameterize the molecules
for molecule in self.molecules:
openmm_topology = molecule.to_topology().to_openmm()
forcefield.createSystem(openmm_topology,
nonbondedMethod=NoCutoff)
# Check database contents
def check_cache(generator, n_expected):
"""
Check database contains number of expected records
Parameters
----------
generator : SmallMoleculeTemplateGenerator
The generator whose cache should be examined
n_expected : int
Number of expected records
"""
from tinydb import TinyDB
db = TinyDB(generator._cache)
table = db.table(generator._database_table_name)
db_entries = table.all()
db.close()
n_entries = len(db_entries)
assert (n_entries == n_expected), \
"Expected {} entries but database has {}\n db contents: {}".format(n_expected, n_entries, db_entries)
check_cache(generator, len(self.molecules))
# Clean up, forcing closure of database
del forcefield, generator
# Create a generator that also uses the database cache but has no molecules
print('Creating new generator with just cache...')
generator = self.TEMPLATE_GENERATOR(cache=cache)
# Check database still contains the molecules we expect
check_cache(generator, len(self.molecules))
# Create a ForceField
forcefield = ForceField()
# Register the template generator
forcefield.registerTemplateGenerator(generator.generator)
# Parameterize the molecules; this should succeed
for molecule in self.molecules:
openmm_topology = molecule.to_topology().to_openmm()
forcefield.createSystem(openmm_topology,
nonbondedMethod=NoCutoff)
def test_jacs_ligands(self):
"""Use template generator to parameterize the Schrodinger JACS set of ligands"""
from simtk.openmm.app import ForceField, NoCutoff
jacs_systems = {
#'bace' : { 'prefix' : 'Bace' },
#'cdk2' : { 'prefix' : 'CDK2' },
'jnk1' : { 'prefix' : 'Jnk1' },
'mcl1' : { 'prefix' : 'MCL1' },
#'p38' : { 'prefix' : 'p38' },
'ptp1b' : { 'prefix' : 'PTP1B' },
'thrombin' : { 'prefix' : 'Thrombin' },
#'tyk2' : { 'prefix' : 'Tyk2' },
}
for system_name in jacs_systems:
prefix = jacs_systems[system_name]['prefix']
# Load molecules
ligand_sdf_filename = get_data_filename(os.path.join('perses_jacs_systems', system_name, prefix + '_ligands.sdf'))
print(f'Reading molecules from {ligand_sdf_filename} ...')
from openforcefield.topology import Molecule
molecules = Molecule.from_file(ligand_sdf_filename, allow_undefined_stereo=True)
# Ensure this is a list
try:
nmolecules = len(molecules)
except TypeError:
molecules = [molecules]
print(f'Read {len(molecules)} molecules from {ligand_sdf_filename}')
#molecules = self.filter_molecules(molecules)
MAX_MOLECULES = len(molecules)
if 'TRAVIS' in os.environ:
MAX_MOLECULES = 3
molecules = molecules[:MAX_MOLECULES]
print(f'{len(molecules)} molecules remain after filtering')
# Create template generator with local cache
cache = os.path.join(get_data_filename(os.path.join('perses_jacs_systems', system_name)), 'cache.json')
generator = self.TEMPLATE_GENERATOR(molecules=molecules, cache=cache)
# Create a ForceField
forcefield = ForceField()
# Register the template generator
forcefield.registerTemplateGenerator(generator.generator)
# Parameterize all molecules
print(f'Caching all molecules for {system_name} at {cache} ...')
n_success = 0
n_failure = 0
for molecule in molecules:
openmm_topology = molecule.to_topology().to_openmm()
try:
forcefield.createSystem(openmm_topology, nonbondedMethod=NoCutoff)
n_success += 1
except Exception as e:
n_failure += 1
print(e)
print(f'{n_failure}/{n_success+n_failure} ligands failed to parameterize for {system_name}')
def test_gaffResidueTemplateGenerator():
"""
Test the GAFF residue template generator.
"""
#
# Test where we generate parameters for only a ligand.
#
# Load the PDB file.
from simtk.openmm.app import PDBFile
pdb_filename = utils.get_data_filename("chemicals/imatinib/imatinib.pdb")
pdb = PDBFile(pdb_filename)
# Create a ForceField object.
gaff_xml_filename = utils.get_data_filename("parameters/gaff.xml")
forcefield = ForceField(gaff_xml_filename)
# Add the residue template generator.
from openmoltools.forcefield_generators import gaffTemplateGenerator
forcefield.registerTemplateGenerator(gaffTemplateGenerator)
# Parameterize system.
system = forcefield.createSystem(pdb.topology, nonbondedMethod=NoCutoff)
# Check potential is finite.
check_potential_is_finite(system, pdb.positions)
# Check energy matches prmtop route.
check_energy_components_vs_prmtop(
prmtop=utils.get_data_filename("chemicals/imatinib/imatinib.prmtop"),
inpcrd=utils.get_data_filename("chemicals/imatinib/imatinib.inpcrd"),
system=system,
)
#
# Test where we generate parameters for only a ligand in a protein.
#
# Load the PDB file.
from simtk.openmm.app import PDBFile
pdb_filename = utils.get_data_filename("chemicals/proteins/T4-lysozyme-L99A-p-xylene-implicit.pdb")
pdb = PDBFile(pdb_filename)
# Create a ForceField object.
gaff_xml_filename = utils.get_data_filename("parameters/gaff.xml")
forcefield = ForceField("amber99sb.xml", gaff_xml_filename)
# Add the residue template generator.
from openmoltools.forcefield_generators import gaffTemplateGenerator
forcefield.registerTemplateGenerator(gaffTemplateGenerator)
# Parameterize system.
system = forcefield.createSystem(pdb.topology, nonbondedMethod=NoCutoff)
# Check potential is finite.
check_potential_is_finite(system, pdb.positions)
def test_gaffResidueTemplateGenerator():
"""
Test the GAFF residue template generator.
"""
#
# Test where we generate parameters for only a ligand.
#
# Load the PDB file.
from simtk.openmm.app import PDBFile
pdb_filename = utils.get_data_filename("chemicals/imatinib/imatinib.pdb")
pdb = PDBFile(pdb_filename)
# Create a ForceField object.
gaff_xml_filename = utils.get_data_filename("parameters/gaff.xml")
forcefield = ForceField(gaff_xml_filename)
# Add the residue template generator.
from openmoltools.forcefield_generators import gaffTemplateGenerator
forcefield.registerTemplateGenerator(gaffTemplateGenerator)
# Parameterize system.
system = forcefield.createSystem(pdb.topology, nonbondedMethod=NoCutoff)
# Check potential is finite.
check_potential_is_finite(system, pdb.positions)
# Check energy matches prmtop route.
check_energy_components_vs_prmtop(
prmtop=utils.get_data_filename('chemicals/imatinib/imatinib.prmtop'),
inpcrd=utils.get_data_filename('chemicals/imatinib/imatinib.inpcrd'),
system=system)
#
# Test where we generate parameters for only a ligand in a protein.
#
# Load the PDB file.
from simtk.openmm.app import PDBFile
pdb_filename = utils.get_data_filename(
"chemicals/proteins/T4-lysozyme-L99A-p-xylene-implicit.pdb")
pdb = PDBFile(pdb_filename)
# Create a ForceField object.
gaff_xml_filename = utils.get_data_filename("parameters/gaff.xml")
forcefield = ForceField('amber99sb.xml', gaff_xml_filename)
# Add the residue template generator.
from openmoltools.forcefield_generators import gaffTemplateGenerator
forcefield.registerTemplateGenerator(gaffTemplateGenerator)
# Parameterize system.
system = forcefield.createSystem(pdb.topology, nonbondedMethod=NoCutoff)
# Check potential is finite.
check_potential_is_finite(system, pdb.positions)
def test_multiple_registration(self):
"""Test registering the template generator with multiple force fields"""
generator = self.TEMPLATE_GENERATOR(molecules=self.molecules)
from simtk.openmm.app import ForceField
NUM_FORCEFIELDS = 2 # number of force fields to test
forcefields = list()
for index in range(NUM_FORCEFIELDS):
forcefield = ForceField()
forcefield.registerTemplateGenerator(generator.generator)
forcefields.append(forcefield)
# Parameterize a molecule in each force field instance
molecule = self.molecules[0]
openmm_topology = molecule.to_topology().to_openmm()
from simtk.openmm.app import NoCutoff
for forcefield in forcefields:
system = forcefield.createSystem(openmm_topology, nonbondedMethod=NoCutoff)
assert system.getNumParticles() == molecule.n_atoms
def test_add_molecules(self):
"""Test that molecules can be added to template generator after its creation"""
# Create a generator that does not know about any molecules
generator = self.TEMPLATE_GENERATOR()
# Create a ForceField
from simtk.openmm.app import ForceField
forcefield = ForceField()
# Register the template generator
forcefield.registerTemplateGenerator(generator.generator)
# Check that parameterizing a molecule fails
molecule = self.molecules[0]
from simtk.openmm.app import NoCutoff
try:
# This should fail with an exception
openmm_topology = molecule.to_topology().to_openmm()
system = forcefield.createSystem(openmm_topology,
nonbondedMethod=NoCutoff)
except ValueError as e:
# Exception 'No template found...' is expected
assert str(e).startswith('No template found')
# Now add the molecule to the generator and ensure parameterization passes
generator.add_molecules(molecule)
openmm_topology = molecule.to_topology().to_openmm()
try:
system = forcefield.createSystem(openmm_topology,
nonbondedMethod=NoCutoff)
except Exception as e:
print(forcefield._atomTypes.keys())
from simtk.openmm.app import PDBFile
PDBFile.writeFile(openmm_topology, molecule.conformers[0])
raise e
assert system.getNumParticles() == molecule.n_atoms
# Add multiple molecules, including repeats
generator.add_molecules(self.molecules)
# Ensure all molecules can be parameterized
for molecule in self.molecules:
openmm_topology = molecule.to_topology().to_openmm()
system = forcefield.createSystem(openmm_topology,
nonbondedMethod=NoCutoff)
assert system.getNumParticles() == molecule.n_atoms
class SystemGenerator(object):
"""
Utility factory to generate OpenMM Systems from Topology objects.
Parameters
----------
forcefields_to_use : list of string
List of the names of ffxml files that will be used in system creation.
forcefield_kwargs : dict of arguments to createSystem, optional
Allows specification of various aspects of system creation.
use_gaff : bool, optional, default=True
If True, will add the GAFF residue template generator.
Examples
--------
>>> from simtk.openmm import app
>>> forcefield_kwargs={ 'nonbondedMethod' : app.NoCutoff, 'implicitSolvent' : None, 'constraints' : None }
>>> system_generator = SystemGenerator(['amber99sbildn.xml'], forcefield_kwargs=forcefield_kwargs)
>>> from openmmtools.testsystems import AlanineDipeptideVacuum
>>> testsystem = AlanineDipeptideVacuum()
>>> system = system_generator.createSystem(testsystem.topology)
"""
def __init__(self,
forcefields_to_use,
forcefield_kwargs=None,
use_gaff=True):
self._forcefield_xmls = forcefields_to_use
self._forcefield_kwargs = forcefield_kwargs if forcefield_kwargs is not None else {}
from simtk.openmm.app import ForceField
self._forcefield = ForceField(*self._forcefield_xmls)
if use_gaff:
self._forcefield.registerTemplateGenerator(gaffTemplateGenerator)
def getForceField(self):
"""
Return the associated ForceField object.
Returns
-------
forcefield : simtk.openmm.app.ForceField
The current ForceField object.
"""
return self._forcefield
def createSystem(self, topology):
"""
Build a system from specified topology object.
Parameters
----------
topology : simtk.openmm.app.Topology object
The topology of the system to construct.
Returns
-------
system : openmm.System
A system object generated from the topology
"""
system = self._forcefield.createSystem(topology,
**self._forcefield_kwargs)
return system
@property
def ffxmls(self):
return self._forcefield_xmls
@property
def forcefield(self):
return self._forcefield
def test_jacs_complexes(self):
"""Use template generator to parameterize the Schrodinger JACS set of complexes"""
# TODO: Uncomment working systems when we have cleaned up the input files
jacs_systems = {
#'bace' : { 'prefix' : 'Bace' },
#'cdk2' : { 'prefix' : 'CDK2' },
#'jnk1' : { 'prefix' : 'Jnk1' },
'mcl1' : { 'prefix' : 'MCL1' },
#'p38' : { 'prefix' : 'p38' },
#'ptp1b' : { 'prefix' : 'PTP1B' },
#'thrombin' : { 'prefix' : 'Thrombin' },
#'tyk2' : { 'prefix' : 'Tyk2' },
}
for system_name in jacs_systems:
prefix = jacs_systems[system_name]['prefix']
# Read molecules
ligand_sdf_filename = get_data_filename(os.path.join('perses_jacs_systems', system_name, prefix + '_ligands.sdf'))
print(f'Reading molecules from {ligand_sdf_filename} ...')
from openforcefield.topology import Molecule
molecules = Molecule.from_file(ligand_sdf_filename, allow_undefined_stereo=True)
try:
nmolecules = len(molecules)
except TypeError:
molecules = [molecules]
print(f'Read {len(molecules)} molecules from {ligand_sdf_filename}')
# Read ParmEd Structures
import parmed
from simtk import unit
protein_pdb_filename = get_data_filename(os.path.join('perses_jacs_systems', system_name, prefix + '_protein.pdb'))
from simtk.openmm.app import PDBFile
print(f'Reading protein from {protein_pdb_filename} ...')
#protein_structure = parmed.load_file(protein_pdb_filename) # NOTE: This mis-interprets distorted geometry and sequentially-numbered residues that span chain breaks
pdbfile = PDBFile(protein_pdb_filename)
protein_structure = parmed.openmm.load_topology(pdbfile.topology, xyz=pdbfile.positions.value_in_unit(unit.angstroms))
ligand_structures = parmed.load_file(ligand_sdf_filename)
try:
nmolecules = len(ligand_structures)
except TypeError:
ligand_structures = [ligand_structures]
assert len(ligand_structures) == len(molecules)
# Filter molecules
if 'TRAVIS' in os.environ:
MAX_MOLECULES = 3
else:
MAX_MOLECULES = 6
molecules = molecules[:MAX_MOLECULES]
ligand_structures = ligand_structures[:MAX_MOLECULES]
print(f'{len(molecules)} molecules remain after filtering')
# Create complexes
complex_structures = [ (protein_structure + ligand_structure) for ligand_structure in ligand_structures ]
# Create template generator with local cache
cache = os.path.join(get_data_filename(os.path.join('perses_jacs_systems', system_name)), 'cache.json')
generator = self.TEMPLATE_GENERATOR(molecules=molecules, cache=cache)
# Create a ForceField
from simtk.openmm.app import ForceField
forcefield = ForceField(*self.amber_forcefields)
# Register the template generator
forcefield.registerTemplateGenerator(generator.generator)
# Parameterize all complexes
print(f'Caching all molecules for {system_name} at {cache} ...')
for ligand_index, complex_structure in enumerate(complex_structures):
openmm_topology = complex_structure.topology
molecule = molecules[ligand_index]
# Delete hydrogens from terminal protein residues
# TODO: Fix the input files so we don't need to do this
from simtk.openmm import app
modeller = app.Modeller(complex_structure.topology, complex_structure.positions)
residues = [residue for residue in modeller.topology.residues() if residue.name != 'UNL']
termini_ids = [residues[0].id, residues[-1].id]
#hs = [atom for atom in modeller.topology.atoms() if atom.element.symbol in ['H'] and atom.residue.name != 'UNL']
hs = [atom for atom in modeller.topology.atoms() if atom.element.symbol in ['H'] and atom.residue.id in termini_ids]
modeller.delete(hs)
from simtk.openmm.app import PDBFile
modeller.addHydrogens(forcefield)
# Parameterize protein:ligand complex in vacuum
print(f' Parameterizing {system_name} : {molecule.to_smiles()} in vacuum...')
from simtk.openmm.app import NoCutoff
forcefield.createSystem(modeller.topology, nonbondedMethod=NoCutoff)
# Parameterize protein:ligand complex in solvent
print(f' Parameterizing {system_name} : {molecule.to_smiles()} in explicit solvent...')
from simtk.openmm.app import PME
modeller.addSolvent(forcefield, padding=0*unit.angstroms, ionicStrength=300*unit.millimolar)
forcefield.createSystem(modeller.topology, nonbondedMethod=PME)
class SystemGenerator(object):
"""
Utility factory to generate OpenMM Systems from Topology objects.
Parameters
----------
forcefields_to_use : list of string
List of the names of ffxml files that will be used in system creation.
forcefield_kwargs : dict of arguments to createSystem, optional
Allows specification of various aspects of system creation.
use_gaff : bool, optional, default=True
If True, will add the GAFF residue template generator.
Examples
--------
>>> from simtk.openmm import app
>>> forcefield_kwargs={ 'nonbondedMethod' : app.NoCutoff, 'implicitSolvent' : None, 'constraints' : None }
>>> system_generator = SystemGenerator(['amber99sbildn.xml'], forcefield_kwargs=forcefield_kwargs)
>>> from openmmtools.testsystems import AlanineDipeptideVacuum
>>> testsystem = AlanineDipeptideVacuum()
>>> system = system_generator.createSystem(testsystem.topology)
"""
def __init__(self, forcefields_to_use, forcefield_kwargs=None, use_gaff=True):
self._forcefield_xmls = forcefields_to_use
self._forcefield_kwargs = forcefield_kwargs if forcefield_kwargs is not None else {}
from simtk.openmm.app import ForceField
self._forcefield = ForceField(*self._forcefield_xmls)
if use_gaff:
self._forcefield.registerTemplateGenerator(gaffTemplateGenerator)
def getForceField(self):
"""
Return the associated ForceField object.
Returns
-------
forcefield : simtk.openmm.app.ForceField
The current ForceField object.
"""
return self._forcefield
def createSystem(self, topology):
"""
Build a system from specified topology object.
Parameters
----------
topology : simtk.openmm.app.Topology object
The topology of the system to construct.
Returns
-------
system : openmm.System
A system object generated from the topology
"""
system = self._forcefield.createSystem(topology, **self._forcefield_kwargs)
return system
@property
def ffxmls(self):
return self._forcefield_xmls
@property
def forcefield(self):
return self._forcefield