"""
A collection of density physical property definitions.
"""
from propertyestimator.properties import PhysicalProperty
from propertyestimator.properties.plugins import register_estimable_property
from propertyestimator.protocols import coordinates, forcefield, miscellaneous, yank
from propertyestimator.substances import Substance
from propertyestimator.workflow.schemas import WorkflowSchema
from propertyestimator.workflow.utils import ProtocolPath
[docs]@register_estimable_property()
class HostGuestBindingAffinity(PhysicalProperty):
"""A class representation of a host-guest binding affinity property"""
@property
def multi_component_property(self):
"""Returns whether this property is dependant on properties of the
full mixed substance, or whether it is also dependant on the properties
of the individual components also.
"""
return False
[docs] @staticmethod
def get_default_workflow_schema(calculation_layer, options=None):
if calculation_layer == "SimulationLayer":
return HostGuestBindingAffinity.get_default_simulation_workflow_schema(
options
)
return None
[docs] @staticmethod
def get_default_simulation_workflow_schema(options=None):
"""Returns the default workflow to use when estimating this property
from direct simulations.
Parameters
----------
options: WorkflowOptions
The default options to use when setting up the estimation workflow.
Returns
-------
WorkflowSchema
The schema to follow when estimating this property.
"""
schema = WorkflowSchema(property_type=HostGuestBindingAffinity.__name__)
schema.id = "{}{}".format(HostGuestBindingAffinity.__name__, "Schema")
# Initial coordinate and topology setup.
filter_ligand = miscellaneous.FilterSubstanceByRole("filter_ligand")
filter_ligand.input_substance = ProtocolPath("substance", "global")
filter_ligand.component_role = Substance.ComponentRole.Ligand
# We only support substances with a single guest ligand.
filter_ligand.expected_components = 1
schema.protocols[filter_ligand.id] = filter_ligand.schema
# Construct the protocols which will (for now) take as input a set of host coordinates,
# and generate a set of charges for them.
filter_receptor = miscellaneous.FilterSubstanceByRole("filter_receptor")
filter_receptor.input_substance = ProtocolPath("substance", "global")
filter_receptor.component_role = Substance.ComponentRole.Receptor
# We only support substances with a single host receptor.
filter_receptor.expected_components = 1
schema.protocols[filter_receptor.id] = filter_receptor.schema
# Perform docking to position the guest within the host.
perform_docking = coordinates.BuildDockedCoordinates("perform_docking")
perform_docking.ligand_substance = ProtocolPath(
"filtered_substance", filter_ligand.id
)
perform_docking.receptor_coordinate_file = ProtocolPath(
"receptor_mol2", "global"
)
schema.protocols[perform_docking.id] = perform_docking.schema
# Solvate the docked structure using packmol
filter_solvent = miscellaneous.FilterSubstanceByRole("filter_solvent")
filter_solvent.input_substance = ProtocolPath("substance", "global")
filter_solvent.component_role = Substance.ComponentRole.Solvent
schema.protocols[filter_solvent.id] = filter_solvent.schema
solvate_complex = coordinates.SolvateExistingStructure("solvate_complex")
solvate_complex.max_molecules = 1000
solvate_complex.substance = ProtocolPath(
"filtered_substance", filter_solvent.id
)
solvate_complex.solute_coordinate_file = ProtocolPath(
"docked_complex_coordinate_path", perform_docking.id
)
schema.protocols[solvate_complex.id] = solvate_complex.schema
# Assign force field parameters to the solvated complex system.
build_solvated_complex_system = forcefield.BuildSmirnoffSystem(
"build_solvated_complex_system"
)
build_solvated_complex_system.force_field_path = ProtocolPath(
"force_field_path", "global"
)
build_solvated_complex_system.coordinate_file_path = ProtocolPath(
"coordinate_file_path", solvate_complex.id
)
build_solvated_complex_system.substance = ProtocolPath("substance", "global")
build_solvated_complex_system.charged_molecule_paths = [
ProtocolPath("receptor_mol2", "global")
]
schema.protocols[
build_solvated_complex_system.id
] = build_solvated_complex_system.schema
# Solvate the ligand using packmol
solvate_ligand = coordinates.SolvateExistingStructure("solvate_ligand")
solvate_ligand.max_molecules = 1000
solvate_ligand.substance = ProtocolPath("filtered_substance", filter_solvent.id)
solvate_ligand.solute_coordinate_file = ProtocolPath(
"docked_ligand_coordinate_path", perform_docking.id
)
schema.protocols[solvate_ligand.id] = solvate_ligand.schema
# Assign force field parameters to the solvated ligand system.
build_solvated_ligand_system = forcefield.BuildSmirnoffSystem(
"build_solvated_ligand_system"
)
build_solvated_ligand_system.force_field_path = ProtocolPath(
"force_field_path", "global"
)
build_solvated_ligand_system.coordinate_file_path = ProtocolPath(
"coordinate_file_path", solvate_ligand.id
)
build_solvated_ligand_system.substance = ProtocolPath("substance", "global")
schema.protocols[
build_solvated_ligand_system.id
] = build_solvated_ligand_system.schema
# Employ YANK to estimate the binding free energy.
yank_protocol = yank.LigandReceptorYankProtocol("yank_protocol")
yank_protocol.thermodynamic_state = ProtocolPath(
"thermodynamic_state", "global"
)
yank_protocol.number_of_iterations = 2000
yank_protocol.steps_per_iteration = 500
yank_protocol.checkpoint_interval = 10
yank_protocol.verbose = True
yank_protocol.force_field_path = ProtocolPath("force_field_path", "global")
yank_protocol.ligand_residue_name = ProtocolPath(
"ligand_residue_name", perform_docking.id
)
yank_protocol.receptor_residue_name = ProtocolPath(
"receptor_residue_name", perform_docking.id
)
yank_protocol.solvated_ligand_coordinates = ProtocolPath(
"coordinate_file_path", solvate_ligand.id
)
yank_protocol.solvated_ligand_system = ProtocolPath(
"system_path", build_solvated_ligand_system.id
)
yank_protocol.solvated_complex_coordinates = ProtocolPath(
"coordinate_file_path", solvate_complex.id
)
yank_protocol.solvated_complex_system = ProtocolPath(
"system_path", build_solvated_complex_system.id
)
schema.protocols[yank_protocol.id] = yank_protocol.schema
# Define where the final values come from.
schema.final_value_source = ProtocolPath(
"estimated_free_energy", yank_protocol.id
)
# output_to_store = WorkflowOutputToStore()
#
# output_to_store.trajectory_file_path = ProtocolPath('output_trajectory_path',
# extract_uncorrelated_trajectory.id)
# output_to_store.coordinate_file_path = ProtocolPath('output_coordinate_file',
# converge_uncertainty.id, npt_production.id)
#
# output_to_store.statistics_file_path = ProtocolPath('output_statistics_path',
# extract_uncorrelated_statistics.id)
#
# output_to_store.statistical_inefficiency = ProtocolPath('statistical_inefficiency', converge_uncertainty.id,
# extract_density.id)
#
# schema.outputs_to_store = {'full_system': output_to_store}
return schema