def test_packmol_simulation_ternary():
smiles_list = ["Cc1ccccc1", "c1ccccc1", "CC"]
pdb_filenames = []
ligand_trajectories, ffxml = utils.smiles_to_mdtraj_ffxml(smiles_list)
for k, ligand_traj in enumerate(ligand_trajectories):
pdb_filename = tempfile.mktemp(suffix=".pdb")
ligand_traj.save(pdb_filename)
pdb_filenames.append(pdb_filename)
pdb_filenames = pdb_filenames[0:2] + [ligand_traj] # Test passing BOTH pdb filenames and trajectories as input.
trj = packmol.pack_box(pdb_filenames, [6, 11, 23])
xyz = trj.openmm_positions(0)
top = trj.top.to_openmm()
top.setUnitCellDimensions(mm.Vec3(*trj.unitcell_lengths[0])*u.nanometer)
forcefield = app.ForceField(ffxml)
temperature = 300 * u.kelvin
friction = 0.1 / u.picosecond
timestep = 0.1 * u.femtosecond
system = forcefield.createSystem(top, nonbondedMethod=app.PME, nonbondedCutoff=1.0 * u.nanometers, constraints=None)
integrator = mm.LangevinIntegrator(temperature, friction, timestep)
simulation = app.Simulation(top, system, integrator)
simulation.context.setPositions(xyz)
simulation.step(25)
def test_amber_binary_mixture():
sustiva_filename = utils.get_data_filename("chemicals/etoh/etoh.mol2")
etoh_filename = utils.get_data_filename("chemicals/etoh/etoh_renamed.mol2")
trj0, trj1 = md.load(sustiva_filename), md.load(etoh_filename)
# Hack to assign unique residue names that are consistent with contents of mol2 files
trj0.top.residue(0).name = "LIG"
trj1.top.residue(0).name = "LI2"
trj_list = [trj0, trj1]
with utils.enter_temp_directory(
): # Prevents creating tons of GAFF files everywhere.
box_filename = "./box.pdb"
box_trj = packmol.pack_box(trj_list, [25, 50])
box_trj.save(box_filename)
gaff_mol2_filename0, frcmod_filename0 = amber.run_antechamber(
"sustiva", sustiva_filename, charge_method=None)
gaff_mol2_filename1, frcmod_filename1 = amber.run_antechamber(
"etoh", etoh_filename, charge_method=None)
mol2_filenames = [gaff_mol2_filename0, gaff_mol2_filename1]
frcmod_filenames = [frcmod_filename0, frcmod_filename1]
prmtop_filename = "./out.prmtop"
inpcrd_filename = "./out.inpcrd"
tleap_cmd = amber.build_mixture_prmtop(mol2_filenames,
frcmod_filenames, box_filename,
prmtop_filename,
inpcrd_filename)
print(tleap_cmd)
def _via_helper_other_solvent(cls, density, num_solvent, **kwargs):
from openmoltools import packmol
density = density.value_in_unit(unit.gram / unit.milliliter)
if cls.backend == "openeye":
box_size = packmol.approximate_volume_by_density(
[cls.smiles, cls.solvent_smiles], [1, num_solvent],
density=density,
box_scaleup_factor=cls.box_scaleup_factor,
box_buffer=cls.default_padding)
else:
box_size = approximate_volume_by_density(
[cls.smiles, cls.solvent_smiles], [1, num_solvent],
density=density,
box_scaleup_factor=cls.box_scaleup_factor,
box_buffer=cls.default_padding)
packmol_out = packmol.pack_box(
[cls.pdb_filename, cls.solvent_pdb_filename], [1, num_solvent],
box_size=box_size)
import mdtraj as md
cls.system_pmd = cls.ligand_pmd + (cls.solvent_pmd * num_solvent)
cls.system_pmd.positions = packmol_out.openmm_positions(0)
cls.system_pmd.box_vectors = packmol_out.openmm_boxes(0)
try:
# TODO should maybe delete the higher parent level? i.e. -2?
shutil.rmtree("/".join(cls.pdb_filename.split("/")[:-1]))
shutil.rmtree("/".join(cls.solvent_pdb_filename.split("/")[:-1]))
del cls.ligand_pmd, cls.solvent_pmd
except Exception as e:
print("Error due to : {}".format(e))
cls.system_pmd.title = cls.smiles
return cls.system_pmd
def test_amber_box():
etoh_filename = utils.get_data_filename("chemicals/etoh/etoh.mol2")
trj_list = [md.load(etoh_filename)]
with utils.enter_temp_directory(
): # Prevents creating tons of GAFF files everywhere.
box_filename = "./box.pdb"
box_trj = packmol.pack_box(trj_list, [50])
box_trj.save(box_filename)
gaff_mol2_filename1, frcmod_filename1 = amber.run_antechamber(
"etoh", etoh_filename, charge_method=None)
mol2_filenames = [gaff_mol2_filename1]
frcmod_filenames = [frcmod_filename1]
prmtop_filename = "./out.prmtop"
inpcrd_filename = "./out.inpcrd"
tleap_cmd = amber.build_mixture_prmtop(mol2_filenames,
frcmod_filenames, box_filename,
prmtop_filename,
inpcrd_filename)
print(tleap_cmd)
def test_amber_binary_mixture():
sustiva_filename = utils.get_data_filename("chemicals/etoh/etoh.mol2")
etoh_filename = utils.get_data_filename("chemicals/etoh/etoh_renamed.mol2")
trj0, trj1 = md.load(sustiva_filename), md.load(etoh_filename)
# Hack to assign unique residue names that are consistent with contents of mol2 files
trj0.top.residue(0).name = "LIG"
trj1.top.residue(0).name = "LI2"
trj_list = [trj0, trj1]
with utils.enter_temp_directory(): # Prevents creating tons of GAFF files everywhere.
box_filename = "./box.pdb"
box_trj = packmol.pack_box(trj_list, [25, 50])
box_trj.save(box_filename)
gaff_mol2_filename0, frcmod_filename0 = amber.run_antechamber("sustiva", sustiva_filename, charge_method=None)
gaff_mol2_filename1, frcmod_filename1 = amber.run_antechamber("etoh", etoh_filename, charge_method=None)
mol2_filenames = [gaff_mol2_filename0, gaff_mol2_filename1]
frcmod_filenames = [frcmod_filename0, frcmod_filename1]
prmtop_filename = "./out.prmtop"
inpcrd_filename = "./out.inpcrd"
tleap_cmd = amber.build_mixture_prmtop(mol2_filenames, frcmod_filenames, box_filename, prmtop_filename, inpcrd_filename)
print(tleap_cmd)
def mixture_setup(molfiles,resnames,nmols,boxsize,solvate=True):
"""
Function that generalises the function 'nanopipeline' for general mixtures.
Starting with the mol2 files of drug and dye, the molecules are parametrised, assembled uniformly in
cubic box, and AMBER prmtop and inpcrd files are created for the system.
Parameters
----------
molfiles : list of str
the mol2 file name of the compounds, with or without hydrogens
resnames : list of str
the residue names you want for the molecules residue name and output file naming schemes
nmols : list of int
the number of molecules you want in the box, excluding water and ions
boxsize: int
the length of the cubic box in Angstroms
Returns
-------
out.inpcrd and out.out.prmtop are created in the working directory, as well gaff output files
"""
# Parmetrizing with antechamber via openeye:
for i in range(len(molfiles)): parametrize_mol(molfiles[i],resnames[i])
# Creating box of drugs and dye. Packmol requires PDB files
for i in range(len(molfiles)): mol2pdb(resnames[i]+'_gaff.mol2')
molfiles_pdb = [mol + '_gaff.pdb' for mol in resnames]
box = packmol.pack_box(molfiles_pdb, nmols, tolerance=2.0, box_size=boxsize)
box.save('box.pdb')
# Running tleap to create out.prmtop out.inpcrd for use with openmm
tleap_input = tleap_mixture(resnames,'box',solvate=solvate,run=True)
def solvate(ase_mol, mol_id, ase_solvent_mol, solvent_id, n_solvent=100):
"""Build solvent sphere around molecule"""
from openmoltools import packmol
# needs to be here rather than global because we sometimes pickle this function and send it to the server to run
# because on importing packmol sets various paths (e.g. where temporary files are kept)
# so we don't want to import those from the local session to the cluster
##File paths
mol_xyz_path = mol_id + '.xyz'
mol_pdb_path = mol_id + '.pdb'
solvent_xyz_path = solvent_id + '.xyz'
solvent_pdb_path = solvent_id + '.pdb'
##File construction of xyz and pdb files
ase_mol.write(mol_xyz_path)
pybel_mol = readfile("xyz", mol_xyz_path).next()
pybel_mol.write('pdb', mol_pdb_path, overwrite=True)
##File construction of solvent pdb files
if not os.path.isfile(solvent_xyz_path):
ase_solvent_mol.write(solvent_xyz_path)
if not os.path.isfile(solvent_pdb_path):
pybel_mol = readfile("xyz", solvent_xyz_path).next()
pybel_mol.write('pdb', solvent_pdb_path)
solute_traj = md.load(mol_pdb_path)
solvent_traj = md.load(solvent_pdb_path)
#currently only works for solvent composed of Hydrogens and Carbons!
#size returns length of box as measured in Angstrom
size = packmol.approximate_volume([mol_pdb_path, solvent_pdb_path], [1,n_solvent])
if ase_mol != ase_solvent_mol:
solvated_traj = packmol.pack_box([solute_traj,solvent_traj],[1,n_solvent],
fix=True, shape='sphere', size=size*0.75,
seed= np.random.randint(2**16), )
else:
solvated_traj = packmol.pack_box([solvent_traj],[n_solvent+1],
fix=True, shape='sphere', size=size*0.75,
seed= np.random.randint(2**16), )
return to_ase_frames(solvated_traj)[0]
def nanopipeline(drugmol2,dyemol2,drugname='LIG',dyename='DYE',ndrugs=10,ndye=20,boxsize=50,neutralize=True,implicit=False):
"""
Starting with the mol2 files of drug and dye, the molecules are parametrised, assembled uniformly in
cubic box, and AMBER prmtop and inpcrd files are created for the system.
Parameters
----------
drugmol2, dyemol2 : str, str
the mol2 file name of the drug/dye, with or without hydrogens
drugname, dyename : str, str
the residue name you want for the drug/dye residue name and output file naming schemes
ndrugs/ndye: int
the number of drug/dye molecules you want in the box
boxsize: int
the length of the cubic box in Angstroms
Returns
-------
out.inpcrd and out.out.prmtop are created in the working directory, as well gaff output files
"""
# Parmetrizing with antechamber via openeye:
parametrize_mol(drugmol2,drugname)
parametrize_mol(dyemol2,dyename)
# Creating box of drugs and dye. Packmol requires PDB files
mol2pdb(drugname+'_gaff.mol2')
mol2pdb(dyename+'_gaff.mol2')
if neutralize == True:
box = packmol.pack_box([drugname+'_gaff.pdb',dyename+'_gaff.pdb','Na.pdb'],[ndrugs,ndye,ndye], tolerance=2.0, box_size=boxsize)
else:
box = packmol.pack_box([drugname+'_gaff.pdb',dyename+'_gaff.pdb'],[ndrugs,ndye], tolerance=2.0, box_size=boxsize)
box.save('box.pdb')
#os.remove(drugname+'_gaff.pdb')
#os.remove(dyename+'_gaff.pdb')
# Running tleap to create out.prmtop out.inpcrd for use with openmm
#tleap_nanosim(drugname,dyename,'box')
if implicit == False:
tleap_mixture([drugname,dyename],'box',solvate=True,implicit=False,run=True)
else:
tleap_mixture([drugname,dyename],'box',solvate=False,implicit=True,run=True)
def _via_helper(cls, density, num_lig, **kwargs):
# TODO !!!!!!!!!!!! approximating volume by density if not possible via rdkit at the moment.
"""
Helper function for via_rdkit or via_openeye
Parameters
----------------
density : simtk.unit
Density of liquid box
num_lig : int
Number of replicates of the molecule
Returns
------------------
system_pmd : parmed.structure
The parameterised system as parmed object
"""
import mdtraj as md # TODO packmol can accept file name as input too, no need for this really
from openmoltools import packmol
density = density.value_in_unit(unit.gram / unit.milliliter)
ligand_mdtraj = md.load(cls.pdb_filename)[0]
try: # TODO better error handling if openeye is not detected
#box_size = packmol.approximate_volume_by_density([smiles], [num_lig], density=density, box_scaleup_factor=1.1, box_buffer=2.0)
box_size = packmol.approximate_volume_by_density(
[cls.smiles], [num_lig],
density=density,
box_scaleup_factor=cls.box_scaleup_factor,
box_buffer=2.0)
except:
box_size = approximate_volume_by_density(
[cls.smiles], [num_lig],
density=density,
box_scaleup_factor=box_scaleup_factor,
box_buffer=2.0)
packmol_out = packmol.pack_box([ligand_mdtraj], [num_lig],
box_size=box_size)
cls.system_pmd = cls.ligand_pmd * num_lig
cls.system_pmd.positions = packmol_out.openmm_positions(0)
cls.system_pmd.box_vectors = packmol_out.openmm_boxes(0)
try:
shutil.rmtree("/".join(cls.pdb_filename.split("/")[:-1]))
del cls.ligand_pmd
except Exception as e:
print("Error due to : {}".format(e))
cls.system_pmd.title = cls.smiles
return cls.system_pmd
def test_binary_mixture_rename():
smiles_string0 = "CCCCCC"
smiles_string1 = "CCCCCCCCC"
with utils.enter_temp_directory(
): # Prevents creating tons of GAFF files everywhere.
mol2_filename0 = "./A.mol2"
frcmod_filename0 = "./A.frcmod"
mol2_filename1 = "./B.mol2"
frcmod_filename1 = "./B.frcmod"
gaff_mol2_filenames = [mol2_filename0, mol2_filename1]
frcmod_filenames = [frcmod_filename0, frcmod_filename1]
prmtop_filename = "./box.prmtop"
inpcrd_filename = "./box.inpcrd"
openmoltools.openeye.smiles_to_antechamber(smiles_string0,
mol2_filename0,
frcmod_filename0)
openmoltools.openeye.smiles_to_antechamber(smiles_string1,
mol2_filename1,
frcmod_filename1)
openmoltools.utils.randomize_mol2_residue_names(gaff_mol2_filenames)
box_pdb_filename = "./box.pdb"
gaff_mol2_filenames = [mol2_filename0, mol2_filename1]
n_monomers = [10, 20]
packed_trj = packmol.pack_box(
[md.load(mol2) for mol2 in gaff_mol2_filenames], n_monomers)
packed_trj.save(box_pdb_filename)
tleap_cmd = openmoltools.amber.build_mixture_prmtop(
gaff_mol2_filenames, frcmod_filenames, box_pdb_filename,
prmtop_filename, inpcrd_filename)
prmtop = app.AmberPrmtopFile(prmtop_filename)
inpcrd = app.AmberInpcrdFile(inpcrd_filename)
system = prmtop.createSystem(nonbondedMethod=app.PME,
nonbondedCutoff=1.0 * u.nanometers,
constraints=app.HBonds)
def test_amber_water_mixture():
water_filename = utils.get_data_filename("chemicals/water/water.mol2")
etoh_filename = utils.get_data_filename("chemicals/etoh/etoh.mol2")
sustiva_filename = utils.get_data_filename("chemicals/sustiva/sustiva.mol2")
with utils.enter_temp_directory(): # Prevents creating tons of GAFF files everywhere.
shutil.copy( water_filename, 'c1.mol2' )
shutil.copy( etoh_filename, 'c2.mol2' )
shutil.copy( sustiva_filename, 'c3.mol2')
water_filename = 'c1.mol2'
etoh_filename = 'c2.mol2'
sustiva_filename = 'c3.mol2'
#Randomize residue names to avoid clashes
utils.randomize_mol2_residue_names( [ water_filename, etoh_filename, sustiva_filename] )
trj0, trj1, trj2 = md.load(water_filename), md.load(etoh_filename), md.load(sustiva_filename)
trj_list = [trj0, trj1, trj2]
box_filename = "./box.pdb"
box_trj = packmol.pack_box(trj_list, [300, 25, 3])
box_trj.save(box_filename)
gaff_mol2_filename0, frcmod_filename0 = amber.run_antechamber("water", water_filename, charge_method=None)
gaff_mol2_filename1, frcmod_filename1 = amber.run_antechamber("etoh", etoh_filename, charge_method=None)
gaff_mol2_filename2, frcmod_filename2 = amber.run_antechamber("sustiva", sustiva_filename, charge_method=None)
mol2_filenames = [gaff_mol2_filename0, gaff_mol2_filename1, gaff_mol2_filename2]
frcmod_filenames = [frcmod_filename0, frcmod_filename1, frcmod_filename2]
prmtop_filename = "./out.prmtop"
inpcrd_filename = "./out.inpcrd"
shutil.copy(box_filename, 'renamed.pdb')
tleap_cmd = amber.build_mixture_prmtop(mol2_filenames, frcmod_filenames, 'renamed.pdb', prmtop_filename, inpcrd_filename)
print(tleap_cmd)
#Also do here for case of GAFF water
tleap_cmd = amber.build_mixture_prmtop(mol2_filenames, frcmod_filenames, box_filename, prmtop_filename, inpcrd_filename, water_model = None)
print(tleap_cmd)
#Also do here for case of SPC
tleap_cmd = amber.build_mixture_prmtop(mol2_filenames, frcmod_filenames, 'renamed.pdb', prmtop_filename, inpcrd_filename, water_model = 'SPC')
print(tleap_cmd)
def test_packmol_simulation_ternary_bydensity():
smiles_list = ["Cc1ccccc1", "c1ccccc1", "CC"]
pdb_filenames = []
ligand_trajectories, ffxml = utils.smiles_to_mdtraj_ffxml(smiles_list)
for k, ligand_traj in enumerate(ligand_trajectories):
pdb_filename = tempfile.mktemp(suffix=".pdb")
ligand_traj.save(pdb_filename)
pdb_filenames.append(pdb_filename)
pdb_filenames = pdb_filenames[0:2] + [
ligand_traj
] # Test passing BOTH pdb filenames and trajectories as input.
size = packmol.approximate_volume_by_density(smiles_list, [12, 22, 46])
trj = packmol.pack_box(pdb_filenames, [12, 22, 46], box_size=size)
# The box size should be set as expected (in nanometers).
assert all(
trj.unitcell_lengths[0] == [size / 10.0, size / 10.0, size / 10.0])
xyz = trj.openmm_positions(0)
top = trj.top.to_openmm()
top.setUnitCellDimensions(mm.Vec3(*trj.unitcell_lengths[0]) * u.nanometer)
forcefield = app.ForceField(ffxml)
temperature = 300 * u.kelvin
friction = 91.0 / u.picosecond
timestep = 0.1 * u.femtosecond
system = forcefield.createSystem(top,
nonbondedMethod=app.PME,
nonbondedCutoff=1.0 * u.nanometers,
constraints=None)
integrator = mm.LangevinIntegrator(temperature, friction, timestep)
simulation = app.Simulation(top, system, integrator)
simulation.context.setPositions(xyz)
simulation.minimizeEnergy()
simulation.step(25)
def test_amber_box():
etoh_filename = utils.get_data_filename("chemicals/etoh/etoh.mol2")
trj_list = [md.load(etoh_filename)]
with utils.enter_temp_directory(): # Prevents creating tons of GAFF files everywhere.
box_filename = "./box.pdb"
box_trj = packmol.pack_box(trj_list, [50])
box_trj.save(box_filename)
gaff_mol2_filename1, frcmod_filename1 = amber.run_antechamber("etoh", etoh_filename, charge_method=None)
mol2_filenames = [gaff_mol2_filename1]
frcmod_filenames = [frcmod_filename1]
prmtop_filename = "./out.prmtop"
inpcrd_filename = "./out.inpcrd"
tleap_cmd = amber.build_mixture_prmtop(mol2_filenames, frcmod_filenames, box_filename, prmtop_filename, inpcrd_filename)
print(tleap_cmd)
def create_pdb_files(molecule_smiles, molecule_mol2_filepath,
water_mol2_filepath, vacuum_pdb_filepath,
solvated_pdb_filepath):
"""Create vacuum and solvated molecule box and save in PDB format.
The function uses packmol to solvate the molecule in 1309 waters.
Parameters
----------
molecule_smiles : str
SMILES string for the molecule.
molecule_mol2_filepath : str
Path to the mol2 file describing the molecule to solvate.
water_mol2_filepath : str
Path to the mol2 file describing the water molecule geometry.
vacuum_pdb_filepath : str
Output path for the PDB file describing the molecule in vacuum.
solvated_pdb_filepath : str
Output path for the PDB file of the solvated molecule.
"""
n_monomers = [1, 1309] # molecule, waters
mol_traj = md.load(molecule_mol2_filepath)
water_traj = md.load(water_mol2_filepath)
# Export molecule in PDB format for vacuum calculation.
mol_traj.save_pdb(vacuum_pdb_filepath)
# Estimate box size based on water density.
box_size = packmol.approximate_volume_by_density([molecule_smiles, 'O'],
n_monomers)
# Solvate molecule and export PDB.
packed_traj = packmol.pack_box([mol_traj, water_traj],
n_molecules_list=[1, 1309],
box_size=box_size)
packed_traj.save_pdb(solvated_pdb_filepath)
def test_packmol_simulation_ternary():
smiles_list = ["Cc1ccccc1", "c1ccccc1", "CC"]
pdb_filenames = []
ligand_trajectories, ffxml = utils.smiles_to_mdtraj_ffxml(smiles_list)
for k, ligand_traj in enumerate(ligand_trajectories):
pdb_filename = tempfile.mktemp(suffix=".pdb")
ligand_traj.save(pdb_filename)
pdb_filenames.append(pdb_filename)
pdb_filenames = pdb_filenames[0:2] + [
ligand_traj
] # Test passing BOTH pdb filenames and trajectories as input.
trj = packmol.pack_box(pdb_filenames, [6, 11, 23])
xyz = trj.openmm_positions(0)
top = trj.top.to_openmm()
top.setUnitCellDimensions(mm.Vec3(*trj.unitcell_lengths[0]) * u.nanometer)
forcefield = app.ForceField(ffxml)
temperature = 300 * u.kelvin
friction = 0.1 / u.picosecond
timestep = 0.1 * u.femtosecond
system = forcefield.createSystem(top,
nonbondedMethod=app.PME,
nonbondedCutoff=1.0 * u.nanometers,
constraints=None)
integrator = mm.LangevinIntegrator(temperature, friction, timestep)
simulation = app.Simulation(top, system, integrator)
simulation.context.setPositions(xyz)
simulation.step(25)
def test_packmol_simulation_ternary_bydensity():
smiles_list = ["Cc1ccccc1", "c1ccccc1", "CC"]
pdb_filenames = []
ligand_trajectories, ffxml = utils.smiles_to_mdtraj_ffxml(smiles_list)
for k, ligand_traj in enumerate(ligand_trajectories):
pdb_filename = tempfile.mktemp(suffix=".pdb")
ligand_traj.save(pdb_filename)
pdb_filenames.append(pdb_filename)
pdb_filenames = pdb_filenames[0:2] + [ligand_traj] # Test passing BOTH pdb filenames and trajectories as input.
size = packmol.approximate_volume_by_density( smiles_list, [12, 22, 46] )
trj = packmol.pack_box(pdb_filenames, [12, 22, 46], box_size = size)
# The box size should be set as expected (in nanometers).
assert all(trj.unitcell_lengths[0] == [size/10.0, size/10.0, size/10.0])
xyz = trj.openmm_positions(0)
top = trj.top.to_openmm()
top.setUnitCellDimensions(mm.Vec3(*trj.unitcell_lengths[0])*u.nanometer)
forcefield = app.ForceField(ffxml)
temperature = 300 * u.kelvin
friction = 91.0 / u.picosecond
timestep = 0.1 * u.femtosecond
system = forcefield.createSystem(top, nonbondedMethod=app.PME, nonbondedCutoff=1.0 * u.nanometers, constraints=None)
integrator = mm.LangevinIntegrator(temperature, friction, timestep)
simulation = app.Simulation(top, system, integrator)
simulation.context.setPositions(xyz)
simulation.minimizeEnergy()
simulation.step(25)
def test_binary_mixture_rename():
smiles_string0 = "CCCCCC"
smiles_string1 = "CCCCCCCCC"
with utils.enter_temp_directory(): # Prevents creating tons of GAFF files everywhere.
mol2_filename0 = "./A.mol2"
frcmod_filename0 = "./A.frcmod"
mol2_filename1 = "./B.mol2"
frcmod_filename1 = "./B.frcmod"
gaff_mol2_filenames = [mol2_filename0, mol2_filename1]
frcmod_filenames = [frcmod_filename0, frcmod_filename1]
prmtop_filename = "./box.prmtop"
inpcrd_filename = "./box.inpcrd"
openmoltools.openeye.smiles_to_antechamber(smiles_string0, mol2_filename0, frcmod_filename0)
openmoltools.openeye.smiles_to_antechamber(smiles_string1, mol2_filename1, frcmod_filename1)
openmoltools.utils.randomize_mol2_residue_names(gaff_mol2_filenames)
box_pdb_filename = "./box.pdb"
gaff_mol2_filenames = [mol2_filename0, mol2_filename1]
n_monomers = [10, 20]
packed_trj = packmol.pack_box([md.load(mol2) for mol2 in gaff_mol2_filenames], n_monomers)
packed_trj.save(box_pdb_filename)
tleap_cmd = openmoltools.amber.build_mixture_prmtop(gaff_mol2_filenames, frcmod_filenames, box_pdb_filename, prmtop_filename, inpcrd_filename)
prmtop = app.AmberPrmtopFile(prmtop_filename)
inpcrd = app.AmberInpcrdFile(inpcrd_filename)
system = prmtop.createSystem(nonbondedMethod=app.PME, nonbondedCutoff=1.0*u.nanometers, constraints=app.HBonds)
def test_amber_water_mixture():
water_filename = utils.get_data_filename("chemicals/water/water.mol2")
etoh_filename = utils.get_data_filename("chemicals/etoh/etoh.mol2")
sustiva_filename = utils.get_data_filename(
"chemicals/sustiva/sustiva.mol2")
with utils.enter_temp_directory(
): # Prevents creating tons of GAFF files everywhere.
shutil.copy(water_filename, 'c1.mol2')
shutil.copy(etoh_filename, 'c2.mol2')
shutil.copy(sustiva_filename, 'c3.mol2')
water_filename = 'c1.mol2'
etoh_filename = 'c2.mol2'
sustiva_filename = 'c3.mol2'
#Randomize residue names to avoid clashes
utils.randomize_mol2_residue_names(
[water_filename, etoh_filename, sustiva_filename])
trj0, trj1, trj2 = md.load(water_filename), md.load(
etoh_filename), md.load(sustiva_filename)
trj_list = [trj0, trj1, trj2]
box_filename = "./box.pdb"
box_trj = packmol.pack_box(trj_list, [300, 25, 3])
box_trj.save(box_filename)
gaff_mol2_filename0, frcmod_filename0 = amber.run_antechamber(
"water", water_filename, charge_method=None)
gaff_mol2_filename1, frcmod_filename1 = amber.run_antechamber(
"etoh", etoh_filename, charge_method=None)
gaff_mol2_filename2, frcmod_filename2 = amber.run_antechamber(
"sustiva", sustiva_filename, charge_method=None)
mol2_filenames = [
gaff_mol2_filename0, gaff_mol2_filename1, gaff_mol2_filename2
]
frcmod_filenames = [
frcmod_filename0, frcmod_filename1, frcmod_filename2
]
prmtop_filename = "./out.prmtop"
inpcrd_filename = "./out.inpcrd"
shutil.copy(box_filename, 'renamed.pdb')
tleap_cmd = amber.build_mixture_prmtop(mol2_filenames,
frcmod_filenames, 'renamed.pdb',
prmtop_filename,
inpcrd_filename)
print(tleap_cmd)
#Also do here for case of GAFF water
tleap_cmd = amber.build_mixture_prmtop(mol2_filenames,
frcmod_filenames,
box_filename,
prmtop_filename,
inpcrd_filename,
water_model=None)
print(tleap_cmd)
#Also do here for case of SPC
tleap_cmd = amber.build_mixture_prmtop(mol2_filenames,
frcmod_filenames,
'renamed.pdb',
prmtop_filename,
inpcrd_filename,
water_model='SPC')
print(tleap_cmd)
def run_md(molecule, solvent_name="chloroform", confId=0):
"""
Uses the PARSLEY forcefield to compute molecule ``molecule`` in a cubic box of solvent at STP.
Details:
- Particle mesh Ewald summation is used (1 nm cutoff)
- Periodic boundary conditions are employed
- Langevin thermostat is employed to regulate temperature
- Box size is automatically scaled to the desired number of solvent molecules
Args:
molecule (openforcefield.topology.Molecule): desired molecule
solvent_name (str): either ``chloroform`` or ``benzene``, for now
confId (int): conformer ID for autogenerated molecular conformers, 0 seems fine by default
Returns:
Nothing, but ``.csv``, ``.hdf5``, and ``.pdb`` files are generated in the current directory.
"""
#### Load in the appropriate Molecule object
off_solute = molecule.to_topology()
omm_solute = off_solute.to_openmm()
mdt_solute = mdt.Topology.from_openmm(omm_solute)
#### Build solvent Molecule object
solvent, density, mw = None, None, None
if solvent_name == "chloroform":
solvent = Molecule.from_smiles("C(Cl)(Cl)Cl")
density = 1.49
mw = 119.38
elif solvent_name == "benzene":
solvent = Molecule.from_smiles("c1ccccc1")
density = 0.879
mw = 78.11
else:
raise ValueError(f"Unknown solvent {solvent_name}!")
solvent.generate_conformers()
off_solvent = solvent.to_topology()
omm_solvent = off_solvent.to_openmm()
mdt_solvent = mdt.Topology.from_openmm(omm_solvent)
#### Calculate box side length
num, length = None, None
if "num" in config:
num = config["num"]
assert isinstance(num,
int), "Need an integer number of solvent molecules."
assert num > 0, "Need a positive number of solvent molecules."
length = (1.6606 * num * mw / density)**(
1 / 3) # 1.6606 = 10^24 (Å**3 per mL) divided by Avogadro's number
elif "length" in config:
length = config["length"]
assert isinstance(length, (int, float)), "Need a numeric side length."
assert length > 0, "Need a positive length."
num = (length**3) * density / (mw * 1.6606)
num = int(num)
else:
raise ValueError("Need ``length`` or ``num`` in config file!")
logger.info(
f"{num} solvent molecules in a cube with {length:.2f} Å sides.")
#### Write solvent and solute to ``.pdb`` files for PACKMOL
solute_pdb = "solute.pdb"
with open(solute_pdb, "w+") as f:
openmm.app.pdbfile.PDBFile.writeFile(omm_solute,
molecule.conformers[confId], f)
solvent_pdb = "solvent.pdb"
with open(solvent_pdb, "w+") as f:
openmm.app.pdbfile.PDBFile.writeFile(omm_solvent,
solvent.conformers[0], f)
#### Use ``openmoltools`` Python wrapper for PACKMOL to fill the box appropriately
mdt_trajectory = pack_box([solute_pdb, solvent_pdb], [1, num],
box_size=length)
#### Convert back to ``openforcefield``
omm_topology = mdt_trajectory.top.to_openmm()
length = length / 10 # OpenMM uses nanometers for some stupid reason
omm_topology.setPeriodicBoxVectors(
((length, 0, 0), (0, length, 0), (0, 0, length)))
off_topology = Topology.from_openmm(omm_topology, [
Molecule.from_topology(off_solute),
Molecule.from_topology(off_solvent)
])
logger.info(f"BOX VECTORS: {off_topology.box_vectors}")
#### Set up the OpenMM system
forcefield.get_parameter_handler('Electrostatics').method = 'PME'
system = forcefield.create_openmm_system(off_topology)
time_step = config["time_step"] * unit.femtoseconds
temperature = config["temperature"] * unit.kelvin
friction = 1 / unit.picosecond
integrator = openmm.LangevinIntegrator(temperature, friction, time_step)
#### Set up the simulation
simulation = openmm.app.Simulation(omm_topology, system, integrator)
logger.info(f"Simulation object created.")
simulation.context.setPositions(mdt_trajectory.openmm_positions(0))
logger.info(f"Positions loaded.")
# pdb_reporter = openmm.app.PDBReporter('trj.pdb', config["pdb_freq"])
hdf5_reporter = mdt.reporters.HDF5Reporter('trj.hdf5', config["hdf5_freq"])
state_data_reporter = openmm.app.StateDataReporter("data.csv",
config["data_freq"],
step=True,
potentialEnergy=True,
temperature=True,
density=True)
# simulation.reporters.append(pdb_reporter)
simulation.reporters.append(hdf5_reporter)
simulation.reporters.append(state_data_reporter)
logger.info("Using Platform: " +
simulation.context.getPlatform().getName())
#### Clean up ``.pdb`` files
os.remove(solute_pdb)
os.remove(solvent_pdb)
logger.info("Minimizing...")
simulation.minimizeEnergy(maxIterations=25)
logger.info("Running...")
w_start = time.time()
p_start = time.process_time()
simulation.step(config["num_steps"])
w_end = time.time()
p_end = time.process_time()
logger.info(
f"Elapsed time {w_end-w_start:.2f} s (CPU: {p_end-p_start:.2f} s)")
logger.info("Done")