def __init__(self, store_directory):
"""
Initialize YANK object with default parameters.
Parameters
----------
store_directory : str
The storage directory in which output NetCDF files are read or written.
"""
# Record that we are not yet initialized.
self._initialized = False
# Store output directory.
self._store_directory = store_directory
# Public attributes.
self.restraint_type = 'flat-bottom' # default to a flat-bottom restraint between the ligand and receptor
self.randomize_ligand = False
self.randomize_ligand_sigma_multiplier = 2.0
self.randomize_ligand_close_cutoff = 1.5 * unit.angstrom # TODO: Allow this to be specified by user.
self.mc_displacement_sigma = 10.0 * unit.angstroms
# Set internal variables.
self._phases = list()
self._store_filenames = dict()
# Default alchemical protocols.
self.default_protocols = dict()
self.default_protocols[
'vacuum'] = AbsoluteAlchemicalFactory.defaultVacuumProtocol()
self.default_protocols[
'solvent-implicit'] = AbsoluteAlchemicalFactory.defaultSolventProtocolImplicit(
)
self.default_protocols[
'complex-implicit'] = AbsoluteAlchemicalFactory.defaultComplexProtocolImplicit(
)
self.default_protocols[
'solvent-explicit'] = AbsoluteAlchemicalFactory.defaultSolventProtocolExplicit(
)
self.default_protocols[
'complex-explicit'] = AbsoluteAlchemicalFactory.defaultComplexProtocolExplicit(
)
# Default options for repex.
self.default_options = dict()
self.default_options['number_of_equilibration_iterations'] = 0
self.default_options['number_of_iterations'] = 100
self.default_options['number_of_iterations'] = 100
self.default_options['timestep'] = 2.0 * unit.femtoseconds
self.default_options['collision_rate'] = 5.0 / unit.picoseconds
self.default_options['minimize'] = False
self.default_options[
'show_mixing_statistics'] = True # this causes slowdown with iteration and should not be used for production
self.default_options['platform'] = None
self.default_options[
'displacement_sigma'] = 1.0 * unit.nanometers # attempt to displace ligand by this stddev will be made each iteration
return
def __init__(self, store_directory, verbose=False):
"""
Initialize YANK object with default parameters.
Parameters
----------
store_directory : str
The storage directory in which output NetCDF files are read or written.
verbose : bool, optional, default=False
If True, will turn on verbose output.
"""
# Record that we are not yet initialized.
self._initialized = False
# Store output directory.
self._store_directory = store_directory
# Public attributes.
self.verbose = verbose
self.restraint_type = 'flat-bottom' # default to a flat-bottom restraint between the ligand and receptor
self.randomize_ligand = True
self.randomize_ligand_sigma_multiplier = 2.0
self.randomize_ligand_close_cutoff = 1.5 * unit.angstrom # TODO: Allow this to be specified by user.
self.mc_displacement_sigma = 10.0 * unit.angstroms
# Set internal variables.
self._phases = list()
self._store_filenames = dict()
# Default alchemical protocols.
self.default_protocols = dict()
self.default_protocols['vacuum'] = AbsoluteAlchemicalFactory.defaultVacuumProtocol()
self.default_protocols['solvent-implicit'] = AbsoluteAlchemicalFactory.defaultSolventProtocolImplicit()
self.default_protocols['complex-implicit'] = AbsoluteAlchemicalFactory.defaultComplexProtocolImplicit()
self.default_protocols['solvent-explicit'] = AbsoluteAlchemicalFactory.defaultSolventProtocolExplicit()
self.default_protocols['complex-explicit'] = AbsoluteAlchemicalFactory.defaultComplexProtocolExplicit()
# Default options for repex.
self.default_options = dict()
self.default_options['number_of_equilibration_iterations'] = 0
self.default_options['number_of_iterations'] = 100
self.default_options['verbose'] = self.verbose
self.default_options['timestep'] = 2.0 * unit.femtoseconds
self.default_options['collision_rate'] = 5.0 / unit.picoseconds
self.default_options['minimize'] = False
self.default_options['show_mixing_statistics'] = True # this causes slowdown with iteration and should not be used for production
self.default_options['platform_names'] = None
self.default_options['displacement_sigma'] = 1.0 * unit.nanometers # attempt to displace ligand by this stddev will be made each iteration
return
def setup_binding_gromacs(args):
"""
Set up ligand binding free energy calculation using gromacs prmtop/inpcrd files.
Parameters
----------
args : dict
Command-line arguments dict from docopt.
Returns
-------
alchemical_phases : list of AlchemicalPhase
Phases (thermodynamic legs) of the calculation.
"""
verbose = args['--verbose']
# Implicit solvent
if args['--gbsa']:
implicitSolvent = getattr(app, args['--gbsa'])
else:
implicitSolvent = None
# Select nonbonded treatment
# TODO: Carefully check whether input file is periodic or not.
if args['--nbmethod']:
nonbondedMethod = getattr(app, args['--nbmethod'])
else:
nonbondedMethod = None
# Constraints
if args['--constraints']:
constraints = getattr(app, args['--constraints'])
else:
constraints = None
# Cutoff
if args['--cutoff']:
nonbondedCutoff = process_unit_bearing_arg(args, '--cutoff', unit.nanometers)
else:
nonbondedCutoff = None
# COM removal
removeCMMotion = False
# Prepare phases of calculation.
phase_prefixes = ['solvent', 'complex'] # list of calculation phases (thermodynamic legs) to set up
components = ['ligand', 'receptor', 'solvent'] # components of the binding system
systems = dict() # systems[phase] is the System object associated with phase 'phase'
topologies = dict() # topologies[phase] is the Topology object associated with phase 'phase'
positions = dict() # positions[phase] is a list of coordinates associated with phase 'phase'
atom_indices = dict() # ligand_atoms[phase] is a list of ligand atom indices associated with phase 'phase'
setup_directory = args['--setupdir'] # Directory where prmtop/inpcrd files are to be found
for phase_prefix in phase_prefixes:
if verbose: logger.info("reading phase %s: " % phase_prefix)
# Read gromacs input files.
gro_filename = os.path.join(setup_directory, '%s.gro' % phase_prefix)
top_filename = os.path.join(setup_directory, '%s.top' % phase_prefix)
if verbose: logger.info('reading gromacs .gro file: %s' % gro_filename)
gro = app.GromacsGroFile(gro_filename)
if verbose: logger.info('reading gromacs .top file "%s" using gromacs include directory "%s"' % (top_filename, args['--gromacsinclude']))
top = app.GromacsTopFile(top_filename, unitCellDimensions=gro.getUnitCellDimensions(), includeDir=args['--gromacsinclude'])
# Assume explicit solvent.
# TODO: Modify this if we can have implicit solvent.
is_periodic = True
phase_suffix = 'explicit'
# Adjust nonbondedMethod.
# TODO: Ensure that selected method is appropriate.
if nonbondedMethod == None:
if is_periodic:
nonbondedMethod = app.CutoffPeriodic
else:
nonbondedMethod = app.NoCutoff
# TODO: Check to make sure both prmtop and inpcrd agree on explicit/implicit.
phase = '%s-%s' % (phase_prefix, phase_suffix)
systems[phase] = top.createSystem(nonbondedMethod=nonbondedMethod, nonbondedCutoff=nonbondedCutoff, constraints=constraints, removeCMMotion=removeCMMotion)
topologies[phase] = top.topology
positions[phase] = gro.getPositions(asNumpy=True)
# Check to make sure number of atoms match between prmtop and inpcrd.
prmtop_natoms = systems[phase].getNumParticles()
inpcrd_natoms = positions[phase].shape[0]
if prmtop_natoms != inpcrd_natoms:
raise Exception("Atom number mismatch: prmtop %s has %d atoms; inpcrd %s has %d atoms." % (prmtop_filename, prmtop_natoms, inpcrd_filename, inpcrd_natoms))
# Find ligand atoms and receptor atoms.
ligand_dsl = args['--ligand'] # MDTraj DSL that specifies ligand atoms
atom_indices[phase] = find_components(systems[phase], top.topology, ligand_dsl)
phases = systems.keys()
alchemical_phases = [None, None]
protocols = {'complex-explicit': AbsoluteAlchemicalFactory.defaultComplexProtocolExplicit(),
'solvent-explicit': AbsoluteAlchemicalFactory.defaultSolventProtocolImplicit()}
for i, name in enumerate(phases):
alchemical_phases[i] = AlchemicalPhase(name, systems[name], topologies[name],
positions[name], atom_indices[name],
protocols[name])
return alchemical_phases
def setup_binding_amber(args):
"""
Set up ligand binding free energy calculation using AMBER prmtop/inpcrd files.
Parameters
----------
args : dict
Command-line arguments dict from docopt.
Returns
-------
alchemical_phases : list of AlchemicalPhase
Phases (thermodynamic legs) of the calculation.
"""
verbose = args['--verbose']
setup_directory = args['--setupdir'] # Directory where prmtop/inpcrd files are to be found
system_parameters = {} # parameters to pass to prmtop.createSystem
# Implicit solvent
if args['--gbsa']:
system_parameters['implicitSolvent'] = getattr(app, args['--gbsa'])
# Select nonbonded treatment
if args['--nbmethod']:
system_parameters['nonbondedMethod'] = getattr(app, args['--nbmethod'])
# Constraints
if args['--constraints']:
system_parameters['constraints'] = getattr(app, args['--constraints'])
# Cutoff
if args['--cutoff']:
system_parameters['nonbondedCutoff'] = process_unit_bearing_arg(args, '--cutoff', unit.nanometers)
# Determine if this will be an explicit or implicit solvent simulation
if ('nonbondedMethod' in system_parameters and
system_parameters['nonbondedMethod'] != app.NoCutoff):
phases_names = ['complex-explicit', 'solvent-explicit']
protocols = [AbsoluteAlchemicalFactory.defaultComplexProtocolExplicit(),
AbsoluteAlchemicalFactory.defaultSolventProtocolExplicit()]
else:
phases_names = ['complex-implicit', 'solvent-implicit']
protocols = [AbsoluteAlchemicalFactory.defaultComplexProtocolImplicit(),
AbsoluteAlchemicalFactory.defaultSolventProtocolImplicit()]
# Prepare Yank arguments
alchemical_phases = [None, None]
setup_directory = os.path.join(setup_directory, '') # add final slash character
system_files_paths = [[setup_directory + 'complex.inpcrd', setup_directory + 'complex.prmtop'],
[setup_directory + 'solvent.inpcrd', setup_directory + 'solvent.prmtop']]
for i, phase_name in enumerate(phases_names):
positions_file_path = system_files_paths[i][0]
topology_file_path = system_files_paths[i][1]
logger.info("Reading phase {}".format(phase_name))
alchemical_phases[i] = pipeline.prepare_phase(positions_file_path, topology_file_path, args['--ligand'],
system_parameters, verbose=verbose)
alchemical_phases[i].name = phase_name
alchemical_phases[i].protocol = protocols[i]
return alchemical_phases
def __init__(self, store_directory, mpicomm=None, **kwargs):
"""
Initialize YANK object with default parameters.
Parameters
----------
store_directory : str
The storage directory in which output NetCDF files are read or written.
mpicomm : MPI communicator, optional
If an MPI communicator is passed, an MPI simulation will be attempted.
restraint_type : str, optional
Restraint type to add between protein and ligand. Supported types are
'flat-bottom' and 'harmonic'. The second one is available only in
implicit solvent (default: 'flat-bottom').
randomize_ligand : bool, optional
Randomize ligand position when True. Not available in explicit solvent
(default: False).
randomize_ligand_close_cutoff : simtk.unit.Quantity (units: length), optional
Cutoff for ligand position randomization (default: 1.5*unit.angstrom).
randomize_ligand_sigma_multiplier : float, optional
Multiplier for ligand position randomization displacement (default: 2.0).
mc_displacement_sigma : simtk.unit.Quantity (units: length), optional
Maximum displacement for Monte Carlo moves that augment Langevin dynamics
(default: 10.0*unit.angstrom).
Other Parameters
----------------
**kwargs
More options to pass to the ReplicaExchange or AlchemicalFactory classes
on initialization.
See Also
--------
ReplicaExchange.default_parameters : extra parameters accepted.
"""
# Copy kwargs to avoid modifications
parameters = copy.deepcopy(kwargs)
# Record that we are not yet initialized.
self._initialized = False
# Store output directory.
self._store_directory = store_directory
# Save MPI communicator
self._mpicomm = mpicomm
# Set internal variables.
self._phases = list()
self._store_filenames = dict()
# Default alchemical protocols.
self.default_protocols = dict()
self.default_protocols['vacuum'] = AbsoluteAlchemicalFactory.defaultVacuumProtocol()
self.default_protocols['solvent-implicit'] = AbsoluteAlchemicalFactory.defaultSolventProtocolImplicit()
self.default_protocols['complex-implicit'] = AbsoluteAlchemicalFactory.defaultComplexProtocolImplicit()
self.default_protocols['solvent-explicit'] = AbsoluteAlchemicalFactory.defaultSolventProtocolExplicit()
self.default_protocols['complex-explicit'] = AbsoluteAlchemicalFactory.defaultComplexProtocolExplicit()
# Store Yank parameters
for option_name, default_value in self.default_parameters.items():
setattr(self, '_' + option_name, parameters.pop(option_name, default_value))
# Store repex parameters
self._repex_parameters = {par: parameters.pop(par) for par in
ModifiedHamiltonianExchange.default_parameters
if par in parameters}
# Store AlchemicalFactory parameters
self._alchemy_parameters = {par: parameters.pop(par) for par in
inspect.getargspec(AbsoluteAlchemicalFactory.__init__).args
if par in parameters}
# Check for unknown parameters
if len(parameters) > 0:
raise TypeError('got an unexpected keyword arguments {}'.format(
', '.join(parameters.keys())))
if not is_periodic:
options['restraint_type'] = 'harmonic'
# Turn off MC ligand displacement.
options['mc_displacement_sigma'] = None
# Prepare phases of calculation.
phase_prefixes = ['solvent', 'complex'] # list of calculation phases (thermodynamic legs) to set up
components = ['ligand', 'receptor', 'solvent'] # components of the binding system
phase_prefixes = ['complex'] # DEBUG, since 'solvent' doesn't work yet
if is_periodic:
protocols = {'complex': AbsoluteAlchemicalFactory.defaultComplexProtocolExplicit(),
'solvent': AbsoluteAlchemicalFactory.defaultSolventProtocolExplicit()}
else:
protocols = {'complex': AbsoluteAlchemicalFactory.defaultComplexProtocolImplicit(),
'solvent': AbsoluteAlchemicalFactory.defaultSolventProtocolImplicit()}
alchemical_phases = [] # alchemical phases of the calculations
for phase_prefix in phase_prefixes:
# Retain the whole system
if is_periodic:
phase_suffix = 'explicit'
else:
phase_suffix = 'implicit'
# Form phase name.
phase = '%s-%s' % (phase_prefix, phase_suffix)
logger.info("phase %s: " % phase)
# Determine selection phrase for atom subset to be used in this phase.
if phase_prefix == 'solvent':
dsl_to_retain = component_dsl['ligand']
def setup_binding_amber(args):
"""
Set up ligand binding free energy calculation using AMBER prmtop/inpcrd files.
Parameters
----------
args : dict
Command-line arguments dict from docopt.
Returns
-------
alchemical_phases : list of AlchemicalPhase
Phases (thermodynamic legs) of the calculation.
"""
verbose = args['--verbose']
setup_directory = args[
'--setupdir'] # Directory where prmtop/inpcrd files are to be found
system_parameters = {} # parameters to pass to prmtop.createSystem
# Implicit solvent
if args['--gbsa']:
system_parameters['implicitSolvent'] = getattr(app, args['--gbsa'])
# Select nonbonded treatment
if args['--nbmethod']:
system_parameters['nonbondedMethod'] = getattr(app, args['--nbmethod'])
# Constraints
if args['--constraints']:
system_parameters['constraints'] = getattr(app, args['--constraints'])
# Cutoff
if args['--cutoff']:
system_parameters['nonbondedCutoff'] = process_unit_bearing_arg(
args, '--cutoff', unit.nanometers)
# Determine if this will be an explicit or implicit solvent simulation
if ('nonbondedMethod' in system_parameters
and system_parameters['nonbondedMethod'] != app.NoCutoff):
phases_names = ['complex-explicit', 'solvent-explicit']
protocols = [
AbsoluteAlchemicalFactory.defaultComplexProtocolExplicit(),
AbsoluteAlchemicalFactory.defaultSolventProtocolExplicit()
]
else:
phases_names = ['complex-implicit', 'solvent-implicit']
protocols = [
AbsoluteAlchemicalFactory.defaultComplexProtocolImplicit(),
AbsoluteAlchemicalFactory.defaultSolventProtocolImplicit()
]
# Prepare Yank arguments
alchemical_phases = [None, None]
setup_directory = os.path.join(setup_directory,
'') # add final slash character
system_files_paths = [[
setup_directory + 'complex.inpcrd', setup_directory + 'complex.prmtop'
], [
setup_directory + 'solvent.inpcrd', setup_directory + 'solvent.prmtop'
]]
for i, phase_name in enumerate(phases_names):
positions_file_path = system_files_paths[i][0]
topology_file_path = system_files_paths[i][1]
logger.info("Reading phase {}".format(phase_name))
alchemical_phases[i] = pipeline.prepare_phase(positions_file_path,
topology_file_path,
args['--ligand'],
system_parameters,
verbose=verbose)
alchemical_phases[i].name = phase_name
alchemical_phases[i].protocol = protocols[i]
return alchemical_phases
def setup_binding_gromacs(args):
"""
Set up ligand binding free energy calculation using gromacs prmtop/inpcrd files.
Parameters
----------
args : dict
Command-line arguments dict from docopt.
Returns
-------
alchemical_phases : list of AlchemicalPhase
Phases (thermodynamic legs) of the calculation.
"""
verbose = args['--verbose']
# Implicit solvent
if args['--gbsa']:
implicitSolvent = getattr(app, args['--gbsa'])
else:
implicitSolvent = None
# Select nonbonded treatment
# TODO: Carefully check whether input file is periodic or not.
if args['--nbmethod']:
nonbondedMethod = getattr(app, args['--nbmethod'])
else:
nonbondedMethod = None
# Constraints
if args['--constraints']:
constraints = getattr(app, args['--constraints'])
else:
constraints = None
# Cutoff
if args['--cutoff']:
nonbondedCutoff = process_unit_bearing_arg(args, '--cutoff',
unit.nanometers)
else:
nonbondedCutoff = None
# COM removal
removeCMMotion = False
# Prepare phases of calculation.
phase_prefixes = [
'solvent', 'complex'
] # list of calculation phases (thermodynamic legs) to set up
components = ['ligand', 'receptor',
'solvent'] # components of the binding system
systems = dict(
) # systems[phase] is the System object associated with phase 'phase'
topologies = dict(
) # topologies[phase] is the Topology object associated with phase 'phase'
positions = dict(
) # positions[phase] is a list of coordinates associated with phase 'phase'
atom_indices = dict(
) # ligand_atoms[phase] is a list of ligand atom indices associated with phase 'phase'
setup_directory = args[
'--setupdir'] # Directory where prmtop/inpcrd files are to be found
for phase_prefix in phase_prefixes:
if verbose: logger.info("reading phase %s: " % phase_prefix)
# Read gromacs input files.
gro_filename = os.path.join(setup_directory, '%s.gro' % phase_prefix)
top_filename = os.path.join(setup_directory, '%s.top' % phase_prefix)
if verbose: logger.info('reading gromacs .gro file: %s' % gro_filename)
gro = app.GromacsGroFile(gro_filename)
if verbose:
logger.info(
'reading gromacs .top file "%s" using gromacs include directory "%s"'
% (top_filename, args['--gromacsinclude']))
top = app.GromacsTopFile(
top_filename,
unitCellDimensions=gro.getUnitCellDimensions(),
includeDir=args['--gromacsinclude'])
# Assume explicit solvent.
# TODO: Modify this if we can have implicit solvent.
is_periodic = True
phase_suffix = 'explicit'
# Adjust nonbondedMethod.
# TODO: Ensure that selected method is appropriate.
if nonbondedMethod == None:
if is_periodic:
nonbondedMethod = app.CutoffPeriodic
else:
nonbondedMethod = app.NoCutoff
# TODO: Check to make sure both prmtop and inpcrd agree on explicit/implicit.
phase = '%s-%s' % (phase_prefix, phase_suffix)
systems[phase] = top.createSystem(nonbondedMethod=nonbondedMethod,
nonbondedCutoff=nonbondedCutoff,
constraints=constraints,
removeCMMotion=removeCMMotion)
topologies[phase] = top.topology
positions[phase] = gro.getPositions(asNumpy=True)
# Check to make sure number of atoms match between prmtop and inpcrd.
prmtop_natoms = systems[phase].getNumParticles()
inpcrd_natoms = positions[phase].shape[0]
if prmtop_natoms != inpcrd_natoms:
raise Exception(
"Atom number mismatch: prmtop %s has %d atoms; inpcrd %s has %d atoms."
% (prmtop_filename, prmtop_natoms, inpcrd_filename,
inpcrd_natoms))
# Find ligand atoms and receptor atoms.
ligand_dsl = args['--ligand'] # MDTraj DSL that specifies ligand atoms
atom_indices[phase] = find_components(systems[phase], top.topology,
ligand_dsl)
phases = systems.keys()
alchemical_phases = [None, None]
protocols = {
'complex-explicit':
AbsoluteAlchemicalFactory.defaultComplexProtocolExplicit(),
'solvent-explicit':
AbsoluteAlchemicalFactory.defaultSolventProtocolImplicit()
}
for i, name in enumerate(phases):
alchemical_phases[i] = AlchemicalPhase(name, systems[name],
topologies[name],
positions[name],
atom_indices[name],
protocols[name])
return alchemical_phases
