Source code for propertyestimator.protocols.forcefield

"""
A collection of protocols for assigning force field parameters to molecular
systems.
"""
import abc
import io
import logging
import os
import re
import subprocess
from enum import Enum

import numpy as np
import requests
from simtk import openmm
from simtk.openmm import app

from propertyestimator.attributes import UNDEFINED
from propertyestimator.forcefield import (
    ForceFieldSource,
    LigParGenForceFieldSource,
    SmirnoffForceFieldSource,
    TLeapForceFieldSource,
)
from propertyestimator.substances import Substance
from propertyestimator.utils.openmm import pint_quantity_to_openmm
from propertyestimator.utils.utils import (
    get_data_filename,
    has_openeye,
    temporarily_change_directory,
)
from propertyestimator.workflow.attributes import InputAttribute, OutputAttribute
from propertyestimator.workflow.plugins import workflow_protocol
from propertyestimator.workflow.protocols import Protocol

logger = logging.getLogger(__name__)


[docs]@workflow_protocol() class BaseBuildSystem(Protocol, abc.ABC): """The base class for any protocol whose role is to apply a set of force field parameters to a given system. """
[docs] class WaterModel(Enum): """An enum which describes which water model is being used, so that correct charges can be applied. Warnings -------- This is only a temporary addition until full water model support is introduced. """ TIP3P = "TIP3P"
force_field_path = InputAttribute( docstring="The file path to the force field parameters to assign to the system.", type_hint=str, default_value=UNDEFINED, ) coordinate_file_path = InputAttribute( docstring="The file path to the PDB coordinate file which defines the " "topology of the system to which the force field parameters " "will be assigned.", type_hint=str, default_value=UNDEFINED, ) substance = InputAttribute( docstring="The composition of the system.", type_hint=Substance, default_value=UNDEFINED, ) water_model = InputAttribute( docstring="The water model to apply, if any water molecules are present.", type_hint=WaterModel, default_value=WaterModel.TIP3P, ) system_path = OutputAttribute( docstring="The path to the assigned system object.", type_hint=str ) @staticmethod def _append_system(existing_system, system_to_append, index_map=None): """Appends a system object onto the end of an existing system. Parameters ---------- existing_system: simtk.openmm.System, optional The base system to extend. system_to_append: simtk.openmm.System The system to append. index_map: dict of int and int, optional A map to apply to the indices of atoms in the `system_to_append`. This is predominantly to be used when the ordering of the atoms in the `system_to_append` does not match the ordering in the full topology. """ supported_force_types = [ openmm.HarmonicBondForce, openmm.HarmonicAngleForce, openmm.PeriodicTorsionForce, openmm.NonbondedForce, ] number_of_appended_forces = 0 index_offset = existing_system.getNumParticles() # Create an index map if one is not provided. if index_map is None: index_map = {i: i for i in range(system_to_append.getNumParticles())} # Append the particles. for index in range(system_to_append.getNumParticles()): index = index_map[index] existing_system.addParticle(system_to_append.getParticleMass(index)) # Append the constraints for index in range(system_to_append.getNumConstraints()): index_a, index_b, distance = system_to_append.getConstraintParameters(index) index_a = index_map[index_a] index_b = index_map[index_b] existing_system.addConstraint( index_a + index_offset, index_b + index_offset, distance ) # Validate the forces to append. for force_to_append in system_to_append.getForces(): if type(force_to_append) in supported_force_types: continue raise ValueError( f"The system contains an unsupported type of " f"force: {type(force_to_append)}." ) # Append the forces. for force_to_append in system_to_append.getForces(): existing_force = None for force in existing_system.getForces(): if type(force) not in supported_force_types: raise ValueError( f"The existing system contains an unsupported type " f"of force: {type(force)}." ) if type(force_to_append) != type(force): continue existing_force = force break if existing_force is None: existing_force = type(force_to_append)() existing_system.addForce(existing_force) if isinstance(force_to_append, openmm.HarmonicBondForce): # Add the bonds. for index in range(force_to_append.getNumBonds()): index_a, index_b, *parameters = force_to_append.getBondParameters( index ) index_a = index_map[index_a] index_b = index_map[index_b] existing_force.addBond( index_a + index_offset, index_b + index_offset, *parameters ) elif isinstance(force_to_append, openmm.HarmonicAngleForce): # Add the angles. for index in range(force_to_append.getNumAngles()): ( index_a, index_b, index_c, *parameters, ) = force_to_append.getAngleParameters(index) index_a = index_map[index_a] index_b = index_map[index_b] index_c = index_map[index_c] existing_force.addAngle( index_a + index_offset, index_b + index_offset, index_c + index_offset, *parameters, ) elif isinstance(force_to_append, openmm.PeriodicTorsionForce): # Add the torsions. for index in range(force_to_append.getNumTorsions()): ( index_a, index_b, index_c, index_d, *parameters, ) = force_to_append.getTorsionParameters(index) index_a = index_map[index_a] index_b = index_map[index_b] index_c = index_map[index_c] index_d = index_map[index_d] existing_force.addTorsion( index_a + index_offset, index_b + index_offset, index_c + index_offset, index_d + index_offset, *parameters, ) elif isinstance(force_to_append, openmm.NonbondedForce): # Add the vdW parameters for index in range(force_to_append.getNumParticles()): index = index_map[index] existing_force.addParticle( *force_to_append.getParticleParameters(index) ) # Add the 1-2, 1-3 and 1-4 exceptions. for index in range(force_to_append.getNumExceptions()): ( index_a, index_b, *parameters, ) = force_to_append.getExceptionParameters(index) index_a = index_map[index_a] index_b = index_map[index_b] existing_force.addException( index_a + index_offset, index_b + index_offset, *parameters ) number_of_appended_forces += 1 if number_of_appended_forces != system_to_append.getNumForces(): raise ValueError("Not all forces were appended.") def _execute(self, directory, available_resources): raise NotImplementedError()
@workflow_protocol() class TemplateBuildSystem(BaseBuildSystem, abc.ABC): """A base protocol for any protocol which assign parameters to a system by first assigning parameters to each individual component of the system, and then replicating those templates for each instance of the component. """ @staticmethod def _build_tip3p_system(cutoff, cell_vectors): """Builds a `simtk.openmm.System` object containing a single water model Parameters ---------- cutoff: simtk.pint.Quantity The non-bonded cutoff. cell_vectors: simtk.pint.Quantity The full system's cell vectors. Returns ------- simtk.openmm.System The created system. """ force_field_path = get_data_filename("forcefield/tip3p.xml") water_pdb_path = get_data_filename("forcefield/tip3p.pdb") component_pdb_file = app.PDBFile(water_pdb_path) component_topology = component_pdb_file.topology component_topology.setUnitCellDimensions(cell_vectors) # Create the system object. force_field_template = app.ForceField(force_field_path) component_system = force_field_template.createSystem( topology=component_topology, nonbondedMethod=app.PME, nonbondedCutoff=cutoff, constraints=app.HBonds, rigidWater=True, removeCMMotion=False, ) return component_system @staticmethod def _create_empty_system(cutoff): """Creates an empty system object with stub forces. Parameters ---------- cutoff: simtk.unit The non-bonded cutoff. Returns ------- simtk.openmm.System The created system object. """ system = openmm.System() system.addForce(openmm.HarmonicBondForce()) system.addForce(openmm.HarmonicAngleForce()) system.addForce(openmm.PeriodicTorsionForce()) nonbonded_force = openmm.NonbondedForce() nonbonded_force.setCutoffDistance(cutoff) nonbonded_force.setNonbondedMethod(openmm.NonbondedForce.PME) system.addForce(nonbonded_force) return system @abc.abstractmethod def _parameterize_molecule(self, molecule, force_field_source, cutoff): """Parameterize the specified molecule. Parameters ---------- molecule: openforcefield.topology.Molecule The molecule to parameterize. force_field_source: ForceFieldSource The tleap source which describes which parameters to apply. cutoff: simtk.unit The non-bonded cutoff. Returns ------- simtk.openmm.System The parameterized system. """ raise NotImplementedError() def _execute(self, directory, available_resources): from openforcefield.topology import Molecule, Topology force_field_source = ForceFieldSource.from_json(self.force_field_path) cutoff = pint_quantity_to_openmm(force_field_source.cutoff) # Load in the systems topology openmm_pdb_file = app.PDBFile(self.coordinate_file_path) # Create an OFF topology for better insight into the layout of the system # topology. unique_molecules = {} for component in self.substance: unique_molecule = Molecule.from_smiles(component.smiles) unique_molecules[unique_molecule.to_smiles()] = unique_molecule # Parameterize each component in the system. system_templates = {} for index, (smiles, unique_molecule) in enumerate(unique_molecules.items()): if smiles in ["O", "[H]O[H]", "[H][O][H]"]: component_system = self._build_tip3p_system( cutoff, openmm_pdb_file.topology.getUnitCellDimensions(), ) else: component_directory = os.path.join(directory, str(index)) os.makedirs(component_directory, exist_ok=True) with temporarily_change_directory(component_directory): component_system = self._parameterize_molecule( unique_molecule, force_field_source, cutoff ) system_templates[smiles] = component_system # Apply the parameters to the topology. topology = Topology.from_openmm( openmm_pdb_file.topology, unique_molecules.values() ) # Create the full system object from the component templates. system = self._create_empty_system(cutoff) for topology_molecule in topology.topology_molecules: smiles = topology_molecule.reference_molecule.to_smiles() system_template = system_templates[smiles] index_map = {} for index, topology_atom in enumerate(topology_molecule.atoms): index_map[topology_atom.atom.molecule_particle_index] = index # Append the component template to the full system. self._append_system(system, system_template, index_map) if openmm_pdb_file.topology.getPeriodicBoxVectors() is not None: system.setDefaultPeriodicBoxVectors( *openmm_pdb_file.topology.getPeriodicBoxVectors() ) # Serialize the system object. self.system_path = os.path.join(directory, "system.xml") with open(self.system_path, "w") as file: file.write(openmm.XmlSerializer.serialize(system))
[docs]@workflow_protocol() class BuildSmirnoffSystem(BaseBuildSystem): """Parametrise a set of molecules with a given smirnoff force field using the `OpenFF toolkit <https://github.com/openforcefield/openforcefield>`_. """ charged_molecule_paths = InputAttribute( docstring="File paths to mol2 files which contain the charges assigned to " "molecules in the system. This input is helpful when dealing " "with large molecules (such as hosts in host-guest binding " "calculations) whose charges may by needed in multiple places," " and hence should only be calculated once.", type_hint=list, default_value=[], ) apply_known_charges = InputAttribute( docstring="If true, the formal charges of ions and the partial charges of " "the selected water model will be automatically applied to any " "matching molecules in the system.", type_hint=bool, default_value=True, ) @staticmethod def _generate_known_charged_molecules(): """Generates a set of molecules whose charges are known a priori, such as ions, for use in parameterised systems. Notes ----- These are solely to be used as a work around until library charges are fully implemented in the openforcefield toolkit. Todos ----- Remove this method when library charges are fully implemented in the openforcefield toolkit. Returns ------- list of openforcefield.topology.Molecule The molecules with assigned charges. """ from openforcefield.topology import Molecule from simtk import unit as simtk_unit sodium = Molecule.from_smiles("[Na+]") sodium.partial_charges = np.array([1.0]) * simtk_unit.elementary_charge potassium = Molecule.from_smiles("[K+]") potassium.partial_charges = np.array([1.0]) * simtk_unit.elementary_charge calcium = Molecule.from_smiles("[Ca+2]") calcium.partial_charges = np.array([2.0]) * simtk_unit.elementary_charge chlorine = Molecule.from_smiles("[Cl-]") chlorine.partial_charges = np.array([-1.0]) * simtk_unit.elementary_charge water = Molecule.from_smiles("O") water.partial_charges = ( np.array([-0.834, 0.417, 0.417]) * simtk_unit.elementary_charge ) return [sodium, potassium, calcium, chlorine, water] def _execute(self, directory, available_resources): from openforcefield.topology import Molecule, Topology pdb_file = app.PDBFile(self.coordinate_file_path) force_field_source = ForceFieldSource.from_json(self.force_field_path) if not isinstance(force_field_source, SmirnoffForceFieldSource): raise ValueError( "Only SMIRNOFF force fields are supported by this protocol." ) force_field = force_field_source.to_force_field() unique_molecules = [] charged_molecules = [] if self.apply_known_charges: charged_molecules = self._generate_known_charged_molecules() # Load in any additional, user specified charged molecules. for charged_molecule_path in self.charged_molecule_paths: charged_molecule = Molecule.from_file(charged_molecule_path, "MOL2") charged_molecules.append(charged_molecule) for component in self.substance.components: molecule = Molecule.from_smiles(smiles=component.smiles) if molecule is None: raise ValueError(f"{component} could not be converted to a Molecule") unique_molecules.append(molecule) topology = Topology.from_openmm( pdb_file.topology, unique_molecules=unique_molecules ) if len(charged_molecules) > 0: system = force_field.create_openmm_system( topology, charge_from_molecules=charged_molecules ) else: system = force_field.create_openmm_system(topology) if system is None: raise RuntimeError( "Failed to create a system from the specified topology and molecules." ) system_xml = openmm.XmlSerializer.serialize(system) self.system_path = os.path.join(directory, "system.xml") with open(self.system_path, "w") as file: file.write(system_xml)
[docs]@workflow_protocol() class BuildLigParGenSystem(TemplateBuildSystem): """Parametrise a set of molecules with the OPLS-AA/M force field. using a `LigParGen server <http://zarbi.chem.yale.edu/ligpargen/>`_. Notes ----- This protocol is currently a work in progress and as such has limited functionality compared to the more established `BuildSmirnoffSystem` protocol. References ---------- [1] Potential energy functions for atomic-level simulations of water and organic and biomolecular systems. Jorgensen, W. L.; Tirado-Rives, J. Proc. Nat. Acad. Sci. USA 2005, 102, 6665-6670 [2] 1.14*CM1A-LBCC: Localized Bond-Charge Corrected CM1A Charges for Condensed-Phase Simulations. Dodda, L. S.; Vilseck, J. Z.; Tirado-Rives, J.; Jorgensen, W. L. J. Phys. Chem. B, 2017, 121 (15), pp 3864-3870 [3] LigParGen web server: An automatic OPLS-AA parameter generator for organic ligands. Dodda, L. S.;Cabeza de Vaca, I.; Tirado-Rives, J.; Jorgensen, W. L. Nucleic Acids Research, Volume 45, Issue W1, 3 July 2017, Pages W331-W336 """ @staticmethod def _built_template(molecule, force_field_source): """Builds a force field template object. Parameters ---------- molecule: openforcefield.topology.Molecule The molecule to templatize. force_field_source: LigParGenForceFieldSource The tleap source which describes which parameters to apply. Returns ------- simtk.openmm.app.ForceField The force field template. """ initial_request_url = force_field_source.request_url empty_stream = io.BytesIO(b"\r\n") total_charge = molecule.total_charge charge_model = "cm1abcc" if ( force_field_source.preferred_charge_model == LigParGenForceFieldSource.ChargeModel.CM1A_1_14 or not np.isclose(total_charge, 0.0) ): charge_model = "cm1a" if ( force_field_source.preferred_charge_model != LigParGenForceFieldSource.ChargeModel.CM1A_1_14 ): logger.warning( f"The preferred charge model is {str(force_field_source.preferred_charge_model)}, " f"however the system is charged and so the " f"{str(LigParGenForceFieldSource.ChargeModel.CM1A_1_14)} model will be used in its " f"place." ) data_body = { "smiData": (None, molecule.to_smiles()), "molpdbfile": ("", empty_stream), "checkopt": (None, 0), "chargetype": (None, charge_model), "dropcharge": (None, total_charge), } # Perform the initial request for LigParGen to parameterize the molecule. request = requests.post(url=initial_request_url, files=data_body) # Cleanup the empty stream empty_stream.close() if request.status_code != requests.codes.ok: return f"The request failed with return code {request.status_code}." response_content = request.content # Retrieve the server file name. force_field_file_name = re.search( r"value=\"/tmp/(.*?).xml\"", response_content.decode() ) if force_field_file_name is None: return "The request could not successfully be completed." force_field_file_name = force_field_file_name.group(1) # Download the force field xml file. download_request_url = force_field_source.download_url download_force_field_body = { "go": (None, "XML"), "fileout": (None, f"/tmp/{force_field_file_name}.xml"), } request = requests.post( url=download_request_url, files=download_force_field_body ) if request.status_code != requests.codes.ok: return f"The request to download the system xml file failed with return code {request.status_code}." force_field_response = request.content force_field_path = "template.xml" with open(force_field_path, "wb") as file: file.write(force_field_response) return app.ForceField(force_field_path) def _parameterize_molecule(self, molecule, force_field_source, cutoff): """Parameterize the specified molecule. Parameters ---------- force_field_source: LigParGenForceFieldSource The tleap source which describes which parameters to apply. Returns ------- simtk.openmm.System The parameterized system. """ from simtk import unit as simtk_unit template = self._built_template(molecule, force_field_source) off_topology = molecule.to_topology() box_vectors = np.eye(3) * 10.0 openmm_topology = off_topology.to_openmm() openmm_topology.setPeriodicBoxVectors(box_vectors * simtk_unit.nanometer) system = template.createSystem( topology=openmm_topology, nonbondedMethod=app.PME, nonbondedCutoff=cutoff, constraints=app.HBonds, rigidWater=True, removeCMMotion=False, ) with open(f"component.xml", "w") as file: file.write(openmm.XmlSerializer.serialize(system)) return system @staticmethod def _apply_opls_mixing_rules(system): """Applies the OPLS mixing rules to the system. Notes ----- This method is based upon that found in the `LigParGen tutorial <http://zarbi.chem.yale.edu/ligpargen/openMM_tutorial.html>`_. Parameters ---------- system: simtk.openmm.System The system object to apply the OPLS mixing rules to. """ from simtk import unit as simtk_unit forces = [system.getForce(index) for index in range(system.getNumForces())] forces = [force for force in forces if isinstance(force, openmm.NonbondedForce)] for original_force in forces: # Define a custom force with the OPLS mixing rules. custom_force = openmm.CustomNonbondedForce( "4*epsilon*((sigma/r)^12-(sigma/r)^6); " "sigma=sqrt(sigma1*sigma2); " "epsilon=sqrt(epsilon1*epsilon2)" ) if original_force.getNonbondedMethod() == 4: # Check for PME custom_force.setNonbondedMethod( openmm.CustomNonbondedForce.CutoffPeriodic ) else: custom_force.setNonbondedMethod(original_force.getNonbondedMethod()) custom_force.addPerParticleParameter("sigma") custom_force.addPerParticleParameter("epsilon") custom_force.setCutoffDistance(original_force.getCutoffDistance()) system.addForce(custom_force) lennard_jones_parameters = {} for index in range(original_force.getNumParticles()): charge, sigma, epsilon = original_force.getParticleParameters(index) # Copy the original vdW parameters over to the new custom force. lennard_jones_parameters[index] = (sigma, epsilon) custom_force.addParticle([sigma, epsilon]) # Disable the original vdW interactions, but leave the charged interactions # turned on. original_force.setParticleParameters(index, charge, sigma, epsilon * 0) # Update the 1-4 exceptions. for exception_index in range(original_force.getNumExceptions()): ( index_a, index_b, charge, sigma, epsilon, ) = original_force.getExceptionParameters(exception_index) # Disable any 1-2, 1-3, 1-4 exceptions on the custom force, and instead let the # original force handle it. custom_force.addExclusion(index_a, index_b) if not np.isclose( epsilon.value_in_unit(simtk_unit.kilojoule_per_mole), 0.0 ): sigma_14 = np.sqrt( lennard_jones_parameters[index_a][0] * lennard_jones_parameters[index_b][0] ) epsilon_14 = np.sqrt( lennard_jones_parameters[index_a][1] * lennard_jones_parameters[index_b][1] ) original_force.setExceptionParameters( exception_index, index_a, index_b, charge, sigma_14, epsilon_14 ) def _execute(self, directory, available_resources): with open(self.force_field_path) as file: force_field_source = ForceFieldSource.parse_json(file.read()) if not isinstance(force_field_source, LigParGenForceFieldSource): raise ValueError( "Only LigParGen force field sources are supported by this protocol." ) super(BuildLigParGenSystem, self)._execute(directory, available_resources) with open(self.system_path) as file: system = openmm.XmlSerializer.deserialize(file.read()) # Apply the OPLS mixing rules. self._apply_opls_mixing_rules(system) with open(self.system_path, "w") as file: file.write(openmm.XmlSerializer.serialize(system))
[docs]@workflow_protocol() class BuildTLeapSystem(TemplateBuildSystem): """Parametrise a set of molecules with an Amber based force field. using the `tleap package <http://ambermd.org/AmberTools.php>`_. Notes ----- * This protocol is currently a work in progress and as such has limited functionality compared to the more established `BuildSmirnoffSystem` protocol. * This protocol requires the optional `ambertools >=19.0` dependency to be installed. """
[docs] class ChargeBackend(Enum): """The framework to use to assign partial charges. """ OpenEye = "OpenEye" AmberTools = "AmberTools"
charge_backend = InputAttribute( docstring="The backend framework to use to assign partial charges.", type_hint=ChargeBackend, default_value=lambda: BuildTLeapSystem.ChargeBackend.OpenEye if has_openeye() else BuildTLeapSystem.ChargeBackend.AmberTools, ) @staticmethod def _run_tleap(molecule, force_field_source, directory): """Uses tleap to apply parameters to a particular molecule, generating a `.prmtop` and a `.rst7` file with the applied parameters. Parameters ---------- molecule: openforcefield.topology.Molecule The molecule to parameterize. force_field_source: TLeapForceFieldSource The tleap source which describes which parameters to apply. directory: str The directory to store and temporary files / the final parameters in. Returns ------- str The file path to the `prmtop` file. str The file path to the `rst7` file. """ from simtk import unit as simtk_unit # Change into the working directory. with temporarily_change_directory(directory): initial_file_path = "initial.sdf" molecule.to_file(initial_file_path, file_format="SDF") # Save the molecule charges to a file. charges = [ x.value_in_unit(simtk_unit.elementary_charge) for x in molecule.partial_charges ] with open("charges.txt", "w") as file: file.write(" ".join(map(str, charges))) if force_field_source.leap_source == "leaprc.gaff2": amber_type = "gaff2" elif force_field_source.leap_source == "leaprc.gaff": amber_type = "gaff" else: raise ValueError( f"The {force_field_source.leap_source} source is currently " f"unsupported. Only the 'leaprc.gaff2' and 'leaprc.gaff' " f" sources are supported." ) # Run antechamber to find the correct atom types. processed_mol2_path = "antechamber.mol2" antechamber_process = subprocess.Popen( [ "antechamber", "-i", initial_file_path, "-fi", "sdf", "-o", processed_mol2_path, "-fo", "mol2", "-at", amber_type, "-rn", "MOL", "-an", "no", "-pf", "yes", "-c", "rc", "-cf", "charges.txt", ], stdout=subprocess.PIPE, stderr=subprocess.PIPE, ) antechamber_output, antechamber_error = antechamber_process.communicate() antechamber_exit_code = antechamber_process.returncode with open("antechamber_output.log", "w") as file: file.write(f"error code: {antechamber_exit_code}\nstdout:\n\n") file.write("stdout:\n\n") file.write(antechamber_output.decode()) file.write("\nstderr:\n\n") file.write(antechamber_error.decode()) if not os.path.isfile(processed_mol2_path): raise RuntimeError( f"antechamber failed to assign atom types to the input mol2 file " f"({initial_file_path})" ) frcmod_path = None if amber_type == "gaff" or amber_type == "gaff2": # Optionally run parmchk to find any missing parameters. frcmod_path = "parmck2.frcmod" prmchk2_process = subprocess.Popen( [ "parmchk2", "-i", processed_mol2_path, "-f", "mol2", "-o", frcmod_path, "-s", amber_type, ], stdout=subprocess.PIPE, stderr=subprocess.PIPE, ) prmchk2_output, prmchk2_error = prmchk2_process.communicate() prmchk2_exit_code = prmchk2_process.returncode with open("prmchk2_output.log", "w") as file: file.write(f"error code: {prmchk2_exit_code}\nstdout:\n\n") file.write(prmchk2_output.decode()) file.write("\nstderr:\n\n") file.write(prmchk2_error.decode()) if not os.path.isfile(frcmod_path): raise RuntimeError( f"parmchk2 failed to assign missing {amber_type} parameters " f"to the antechamber created mol2 file ({processed_mol2_path})", ) # Build the tleap input file. template_lines = [f"source {force_field_source.leap_source}"] if frcmod_path is not None: template_lines.append(f"loadamberparams {frcmod_path}",) prmtop_file_name = "structure.prmtop" rst7_file_name = "structure.rst7" template_lines.extend( [ f"MOL = loadmol2 {processed_mol2_path}", f'setBox MOL "centers"', "check MOL", f"saveamberparm MOL {prmtop_file_name} {rst7_file_name}", ] ) input_file_path = "tleap.in" with open(input_file_path, "w") as file: file.write("\n".join(template_lines)) # Run tleap. tleap_process = subprocess.Popen( ["tleap", "-s ", "-f ", input_file_path], stdout=subprocess.PIPE ) tleap_output, _ = tleap_process.communicate() tleap_exit_code = tleap_process.returncode with open("tleap_output.log", "w") as file: file.write(f"error code: {tleap_exit_code}\nstdout:\n\n") file.write(tleap_output.decode()) if not os.path.isfile(prmtop_file_name) or not os.path.isfile( rst7_file_name ): raise RuntimeError(f"tleap failed to execute.") with open("leap.log", "r") as file: if re.search( "ERROR|WARNING|Warning|duplicate|FATAL|Could|Fatal|Error", file.read(), ): raise RuntimeError(f"tleap failed to execute.") return ( os.path.join(directory, prmtop_file_name), os.path.join(directory, rst7_file_name), ) def _generate_charges(self, molecule): """Generates a set of partial charges for a molecule using the specified charge backend. Parameters ---------- molecule: openforcefield.topology.Molecule The molecule to assign charges to. """ if self.charge_backend == BuildTLeapSystem.ChargeBackend.OpenEye: from openforcefield.utils.toolkits import OpenEyeToolkitWrapper toolkit_wrapper = OpenEyeToolkitWrapper() elif self.charge_backend == BuildTLeapSystem.ChargeBackend.AmberTools: from openforcefield.utils.toolkits import ( RDKitToolkitWrapper, AmberToolsToolkitWrapper, ToolkitRegistry, ) toolkit_wrapper = ToolkitRegistry( toolkit_precedence=[RDKitToolkitWrapper, AmberToolsToolkitWrapper] ) else: raise ValueError(f"Invalid toolkit specification.") molecule.generate_conformers(toolkit_registry=toolkit_wrapper) molecule.compute_partial_charges_am1bcc(toolkit_registry=toolkit_wrapper) def _parameterize_molecule(self, molecule, force_field_source, cutoff): """Parameterize the specified molecule. Parameters ---------- molecule: openforcefield.topology.Molecule The molecule to parameterize. force_field_source: TLeapForceFieldSource The tleap source which describes which parameters to apply. Returns ------- simtk.openmm.System The parameterized system. """ self._generate_charges(molecule) prmtop_path, _ = BuildTLeapSystem._run_tleap(molecule, force_field_source, "") prmtop_file = openmm.app.AmberPrmtopFile(prmtop_path) system = prmtop_file.createSystem( nonbondedMethod=app.PME, nonbondedCutoff=cutoff, constraints=app.HBonds, rigidWater=True, removeCMMotion=False, ) with open(f"component.xml", "w") as file: file.write(openmm.XmlSerializer.serialize(system)) return system def _execute(self, directory, available_resources): force_field_source = ForceFieldSource.from_json(self.force_field_path) if not isinstance(force_field_source, TLeapForceFieldSource): raise ValueError( "Only TLeap force field sources are supported by this protocol." ) super(BuildTLeapSystem, self)._execute(directory, available_resources)