vdw_lambda=vdw_lambda,
annihilate_coulomb=True,
annihilate_vdw=True))
# Create alchemical states where we turn on charges with full Lennard-Jones.
for coulomb_lambda in coulomb_lambdas:
alchemical_states.append(
AlchemicalState(coulomb_lambda=coulomb_lambda,
vdw_lambda=1.0,
annihilate_coulomb=True,
annihilate_vdw=True))
alchemical_factory = AbsoluteAlchemicalFactory(
reference_system, alchemical_atoms=alchemical_atoms)
systems = alchemical_factory.createPerturbedSystems(
alchemical_states
) # systems[istate] will be the System object corresponding to alchemical intermediate state index 'istate'
nstates = len(systems)
#==============================================================================
# Run simulation.
#==============================================================================
# Initialize NetCDF file to store data.
import netCDF4 as netcdf
ncfile = netcdf.Dataset(filename, 'w', version='NETCDF4')
ncfile.createDimension('iteration', 0) # unlimited number of iterations
ncfile.createDimension('state', nstates) # number of replicas
ncfile.createDimension(
'atom', reference_system.getNumParticles()) # number of atoms in system
ncfile.createDimension('spatial', 3) # number of spatial dimensions
def _create_phase(self, phase, reference_system, positions, atom_indices, thermodynamic_state, protocols=None, options=None, mpicomm=None):
"""
Create a repex object for a specified phase.
Parameters
----------
phase : str
The phase being initialized (one of ['complex', 'solvent', 'vacuum'])
reference_system : simtk.openmm.System
The reference system object from which alchemical intermediates are to be construcfted.
positions : list of simtk.unit.Qunatity objects containing (natoms x 3) positions (as np or lists)
The list of positions to be used to seed replicas in a round-robin way.
atom_indices : dict
atom_indices[phase][component] is the set of atom indices associated with component, where component is ['ligand', 'receptor']
thermodynamic_state : ThermodynamicState
Thermodynamic state from which reference temperature and pressure are to be taken.
protocols : dict of list of AlchemicalState, optional, default=None
If specified, the alchemical protocol protocols[phase] will be used for phase 'phase' instead of the default.
options : dict of str, optional, default=None
If specified, these options will override default repex simulation options.
"""
# Make sure positions argument is a list of coordinate snapshots.
if hasattr(positions, 'unit'):
# Wrap in list.
positions = [positions]
# Check the dimensions of positions.
for index in range(len(positions)):
# Make sure it is recast as a np array.
positions[index] = unit.Quantity(np.array(positions[index] / positions[index].unit), positions[index].unit)
[natoms, ndim] = (positions[index] / positions[index].unit).shape
if natoms != reference_system.getNumParticles():
raise Exception("positions argument must be a list of simtk.unit.Quantity of (natoms,3) lists or np array with units compatible with nanometers.")
# Create metadata storage.
metadata = dict()
# Make a deep copy of the reference system so we don't accidentally modify it.
reference_system = copy.deepcopy(reference_system)
# TODO: Use more general approach to determine whether system is periodic.
is_periodic = self._is_periodic(reference_system)
# Make sure pressure is None if not periodic.
if not is_periodic: thermodynamic_state.pressure = None
# Compute standard state corrections for complex phase.
metadata['standard_state_correction'] = 0.0
# TODO: Do we need to include a standard state correction for other phases in periodic boxes?
if phase == 'complex-implicit':
# Impose restraints for complex system in implicit solvent to keep ligand from drifting too far away from receptor.
if self.verbose: print "Creating receptor-ligand restraints..."
reference_positions = positions[0]
if self.restraint_type == 'harmonic':
restraints = HarmonicReceptorLigandRestraint(thermodynamic_state, reference_system, reference_positions, atom_indices['receptor'], atom_indices['ligand'])
elif self.restraint_type == 'flat-bottom':
restraints = FlatBottomReceptorLigandRestraint(thermodynamic_state, reference_system, reference_positions, atom_indices['receptor'], atom_indices['ligand'])
else:
raise Exception("restraint_type of '%s' is not supported." % self.restraint_type)
force = restraints.getRestraintForce() # Get Force object incorporating restraints
reference_system.addForce(force)
metadata['standard_state_correction'] = restraints.getStandardStateCorrection() # standard state correction in kT
elif phase == 'complex-explicit':
# For periodic systems, we do not use a restraint, but must add a standard state correction for the box volume.
# TODO: What if the box volume fluctuates during the simulation?
box_vectors = reference_system.getDefaultPeriodicBoxVectors()
box_volume = thermodynamic_state._volume(box_vectors)
STANDARD_STATE_VOLUME = 1660.53928 * unit.angstrom**3
metadata['standard_state_correction'] = np.log(STANDARD_STATE_VOLUME / box_volume) # TODO: Check sign.
# Use default alchemical protocols if not specified.
if not protocols:
protocols = self.default_protocols
# Create alchemically-modified states using alchemical factory.
if self.verbose: print "Creating alchemically-modified states..."
factory = AbsoluteAlchemicalFactory(reference_system, ligand_atoms=atom_indices['ligand'])
systems = factory.createPerturbedSystems(protocols[phase])
# Randomize ligand position if requested, but only for implicit solvent systems.
if self.randomize_ligand and (phase == 'complex-implicit'):
if self.verbose: print "Randomizing ligand positions and excluding overlapping configurations..."
randomized_positions = list()
nstates = len(systems)
for state_index in range(nstates):
positions_index = np.random.randint(0, len(positions))
current_positions = positions[positions_index]
new_positions = ModifiedHamiltonianExchange.randomize_ligand_position(current_positions,
atom_indices['receptor'], atom_indices['ligand'],
self.randomize_ligand_sigma_multiplier * restraints.getReceptorRadiusOfGyration(),
self.randomize_ligand_close_cutoff)
randomized_positions.append(new_positions)
positions = randomized_positions
if self.randomize_ligand and (phase == 'complex-explicit'):
print "WARNING: Ligand randomization requested, but will not be performed for explicit solvent simulations."
# Identify whether any atoms will be displaced via MC.
mc_atoms = list()
if 'ligand' in atom_indices:
mc_atoms = atom_indices['ligand']
# Combine simulation options with defaults.
options = dict(self.default_options.items() + options.items())
# Set up simulation.
# TODO: Support MPI initialization?
if self.verbose: print "Creating replica exchange object..."
store_filename = os.path.join(self._store_directory, phase + '.nc')
self._store_filenames[phase] = store_filename
simulation = ModifiedHamiltonianExchange(store_filename, mpicomm=mpicomm)
simulation.create(thermodynamic_state, systems, positions,
displacement_sigma=self.mc_displacement_sigma, mc_atoms=mc_atoms,
options=options, metadata=metadata)
simulation.verbose = self.verbose
# Initialize simulation.
# TODO: Use the right scheme for initializing the simulation without running.
#if self.verbose: print "Initializing simulation..."
#simulation.run(0)
# TODO: Process user-supplied options.
# Clean up simulation.
del simulation
return
def _create_phase(self,
phase,
reference_system,
positions,
atom_indices,
thermodynamic_state,
protocols=None,
options=None,
mpicomm=None):
"""
Create a repex object for a specified phase.
Parameters
----------
phase : str
The phase being initialized (one of ['complex', 'solvent', 'vacuum'])
reference_system : simtk.openmm.System
The reference system object from which alchemical intermediates are to be construcfted.
positions : list of simtk.unit.Qunatity objects containing (natoms x 3) positions (as np or lists)
The list of positions to be used to seed replicas in a round-robin way.
atom_indices : dict
atom_indices[phase][component] is the set of atom indices associated with component, where component is ['ligand', 'receptor']
thermodynamic_state : ThermodynamicState
Thermodynamic state from which reference temperature and pressure are to be taken.
protocols : dict of list of AlchemicalState, optional, default=None
If specified, the alchemical protocol protocols[phase] will be used for phase 'phase' instead of the default.
options : dict of str, optional, default=None
If specified, these options will override default repex simulation options.
"""
# Make sure positions argument is a list of coordinate snapshots.
if hasattr(positions, 'unit'):
# Wrap in list.
positions = [positions]
# Check the dimensions of positions.
for index in range(len(positions)):
# Make sure it is recast as a np array.
positions[index] = unit.Quantity(
np.array(positions[index] / positions[index].unit),
positions[index].unit)
[natoms, ndim] = (positions[index] / positions[index].unit).shape
if natoms != reference_system.getNumParticles():
raise Exception(
"positions argument must be a list of simtk.unit.Quantity of (natoms,3) lists or np array with units compatible with nanometers."
)
# Create metadata storage.
metadata = dict()
# Make a deep copy of the reference system so we don't accidentally modify it.
reference_system = copy.deepcopy(reference_system)
# TODO: Use more general approach to determine whether system is periodic.
is_periodic = self._is_periodic(reference_system)
# Make sure pressure is None if not periodic.
if not is_periodic: thermodynamic_state.pressure = None
# Compute standard state corrections for complex phase.
metadata['standard_state_correction'] = 0.0
# TODO: Do we need to include a standard state correction for other phases in periodic boxes?
if phase == 'complex-implicit':
# Impose restraints for complex system in implicit solvent to keep ligand from drifting too far away from receptor.
if self.verbose: print "Creating receptor-ligand restraints..."
reference_positions = positions[0]
if self.restraint_type == 'harmonic':
restraints = HarmonicReceptorLigandRestraint(
thermodynamic_state, reference_system, reference_positions,
atom_indices['receptor'], atom_indices['ligand'])
elif self.restraint_type == 'flat-bottom':
restraints = FlatBottomReceptorLigandRestraint(
thermodynamic_state, reference_system, reference_positions,
atom_indices['receptor'], atom_indices['ligand'])
else:
raise Exception("restraint_type of '%s' is not supported." %
self.restraint_type)
force = restraints.getRestraintForce(
) # Get Force object incorporating restraints
reference_system.addForce(force)
metadata[
'standard_state_correction'] = restraints.getStandardStateCorrection(
) # standard state correction in kT
elif phase == 'complex-explicit':
# For periodic systems, we do not use a restraint, but must add a standard state correction for the box volume.
# TODO: What if the box volume fluctuates during the simulation?
box_vectors = reference_system.getDefaultPeriodicBoxVectors()
box_volume = thermodynamic_state._volume(box_vectors)
STANDARD_STATE_VOLUME = 1660.53928 * unit.angstrom**3
metadata['standard_state_correction'] = np.log(
STANDARD_STATE_VOLUME / box_volume) # TODO: Check sign.
# Use default alchemical protocols if not specified.
if not protocols:
protocols = self.default_protocols
# Create alchemically-modified states using alchemical factory.
if self.verbose: print "Creating alchemically-modified states..."
factory = AbsoluteAlchemicalFactory(
reference_system, ligand_atoms=atom_indices['ligand'])
systems = factory.createPerturbedSystems(protocols[phase])
# Randomize ligand position if requested, but only for implicit solvent systems.
if self.randomize_ligand and (phase == 'complex-implicit'):
if self.verbose:
print "Randomizing ligand positions and excluding overlapping configurations..."
randomized_positions = list()
nstates = len(systems)
for state_index in range(nstates):
positions_index = np.random.randint(0, len(positions))
current_positions = positions[positions_index]
new_positions = ModifiedHamiltonianExchange.randomize_ligand_position(
current_positions, atom_indices['receptor'],
atom_indices['ligand'],
self.randomize_ligand_sigma_multiplier *
restraints.getReceptorRadiusOfGyration(),
self.randomize_ligand_close_cutoff)
randomized_positions.append(new_positions)
positions = randomized_positions
# Identify whether any atoms will be displaced via MC.
mc_atoms = list()
if 'ligand' in atom_indices:
mc_atoms = atom_indices['ligand']
# Combine simulation options with defaults.
options = dict(self.default_options.items() + options.items())
# Set up simulation.
# TODO: Support MPI initialization?
if self.verbose: print "Creating replica exchange object..."
store_filename = os.path.join(self._store_directory, phase + '.nc')
self._store_filenames[phase] = store_filename
simulation = ModifiedHamiltonianExchange(store_filename,
mpicomm=mpicomm)
simulation.create(thermodynamic_state,
systems,
positions,
displacement_sigma=self.mc_displacement_sigma,
mc_atoms=mc_atoms,
options=options,
metadata=metadata)
simulation.verbose = self.verbose
# Initialize simulation.
# TODO: Use the right scheme for initializing the simulation without running.
#if self.verbose: print "Initializing simulation..."
#simulation.run(0)
# TODO: Process user-supplied options.
# Clean up simulation.
del simulation
return
#
# Create alchemical intermediates.
#
print "Creating alchemical intermediates..."
# Create a factory to produce alchemical intermediates.
ligand_atoms = range(0, 2) # NaCl
from alchemy import AbsoluteAlchemicalFactory
factory = AbsoluteAlchemicalFactory(reference_system,
ligand_atoms=ligand_atoms)
# Get the default protocol for 'denihilating' in complex in explicit solvent.
protocol = factory.defaultComplexProtocolImplicit()
# Create the perturbed systems using this protocol.
systems = factory.createPerturbedSystems(protocol, verbose=True)
#
# Set up replica exchange simulation.
#
print "Setting up replica-exchange simulation..."
# Create reference state.
from thermodynamics import ThermodynamicState
reference_state = ThermodynamicState(reference_system,
temperature=temperature,
pressure=pressure)
# Create simulation.
from repex import HamiltonianExchange
simulation = HamiltonianExchange(reference_state, systems, positions,
print "Creating alchemical intermediates..."
alchemical_atoms = range(nfixed) # atoms to be alchemically modified
alchemical_states = list() # alchemical_states[istate] is the alchemical state lambda specification for alchemical state 'istate'
# Create alchemical states where we turn on Lennard-Jones (via softcore) with zero charge.
for vdw_lambda in vdw_lambdas:
alchemical_states.append( AlchemicalState(coulomb_lambda=0.0, vdw_lambda=vdw_lambda, annihilate_coulomb=True, annihilate_vdw=True) )
# Create alchemical states where we turn on charges with full Lennard-Jones.
for coulomb_lambda in coulomb_lambdas:
alchemical_states.append( AlchemicalState(coulomb_lambda=coulomb_lambda, vdw_lambda=1.0, annihilate_coulomb=True, annihilate_vdw=True) )
alchemical_factory = AbsoluteAlchemicalFactory(reference_system, alchemical_atoms=alchemical_atoms)
systems = alchemical_factory.createPerturbedSystems(alchemical_states) # systems[istate] will be the System object corresponding to alchemical intermediate state index 'istate'
nstates = len(systems)
#==============================================================================
# Run simulation.
#==============================================================================
# Initialize NetCDF file to store data.
import netCDF4 as netcdf
ncfile = netcdf.Dataset(filename, 'w', version='NETCDF4')
ncfile.createDimension('iteration', 0) # unlimited number of iterations
ncfile.createDimension('state', nstates) # number of replicas
ncfile.createDimension('atom', reference_system.getNumParticles()) # number of atoms in system
ncfile.createDimension('spatial', 3) # number of spatial dimensions
ncfile.createVariable('positions', 'f', ('iteration','state','atom','spatial')) # positions (in A)
ncfile.createVariable('box_vectors', 'f', ('iteration','state','spatial','spatial')) # box vectors (in A)
#!/usr/bin/env python """ Create alchemical intermediates for default alchemical protocol for p-xylene in T4 lysozyme L99A in GBSA. """ from alchemy import AbsoluteAlchemicalFactory from openmmtools import testsystems # Create a reference system. print "Creating a reference T4 lysozyme L99A system..." complex = testsystems.LysozymeImplicit() [reference_system, positions] = [complex.system, complex.positions] # Create a factory to produce alchemical intermediates. print "Creating an alchemical factory..." receptor_atoms = range(0,2603) # T4 lysozyme L99A ligand_atoms = range(2603,2621) # p-xylene factory = AbsoluteAlchemicalFactory(reference_system, ligand_atoms=ligand_atoms) # Get the default protocol for 'denihilating' in complex in explicit solvent. protocol = factory.defaultComplexProtocolImplicit() # Create the perturbed systems using this protocol. print "Creating a perturbed system..." systems = factory.createPerturbedSystems(protocol) print "Done."
