def test_gromacs_merge():
etoh_filename = utils.get_data_filename("chemicals/etoh/etoh.mol2")
benzene_filename = utils.get_data_filename("chemicals/benzene/benzene.mol2")
with utils.enter_temp_directory(): #Prevents creating lots of tleap/antechamber files everywhere
#Generate frcmod files, mol2 files
gaff_mol2_filename1, frcmod_filename1 = amber.run_antechamber( "etoh", etoh_filename, charge_method = None)
gaff_mol2_filename2, frcmod_filename2 = amber.run_antechamber( "benzene", benzene_filename, charge_method = None)
#Set file names
prmtop_filename1 = "./out1.prmtop"
prmtop_filename2 = "./out2.prmtop"
crd_filename1 = "./out1.inpcrd"
crd_filename2 = "./out2.inpcrd"
top_filename1 = "./out1.top"
top_filename2 = "./out2.top"
gro_filename1 = "./out1.gro"
gro_filename2 = "./out2.gro"
#Generate AMBER files
amber.run_tleap( 'etoh', gaff_mol2_filename1, frcmod_filename1, prmtop_filename1, crd_filename1 )
amber.run_tleap( 'benzene', gaff_mol2_filename2, frcmod_filename2, prmtop_filename2, crd_filename2 )
#Convert to GROMACS
utils.amber_to_gromacs( "etoh", prmtop_filename1, crd_filename1, out_top = top_filename1, out_gro = gro_filename1 )
utils.amber_to_gromacs( "benzene", prmtop_filename2, crd_filename2, out_top = top_filename2, out_gro = gro_filename2 )
#Merge topologies
gromacs.merge_topologies( [ top_filename1, top_filename2], './combined.top', 'combined', molecule_numbers = [1, 5], molecule_names = ['etoh', 'benzene'] )
#Test editing of molecule numbers in topology file
gromacs.change_molecules_section( './combined.top', './edited.top', ['etoh', 'benzene'], [10, 20] )
def imatinib_timing():
print("Loading imatinib...")
# Load the PDB file.
from simtk.openmm.app import PDBFile
pdb_filename = utils.get_data_filename("chemicals/imatinib/imatinib.pdb")
pdb = PDBFile(pdb_filename)
# Create a ForceField object.
gaff_xml_filename = utils.get_data_filename("parameters/gaff.xml")
forcefield = ForceField(gaff_xml_filename)
# Add the residue template generator.
from openmoltools.forcefield_generators import gaffTemplateGenerator
forcefield.registerTemplateGenerator(gaffTemplateGenerator)
# Parameterize system.
system = forcefield.createSystem(pdb.topology, nonbondedMethod=NoCutoff)
integrator = openmm.LangevinIntegrator(300 * unit.kelvin,
5.0 / unit.picoseconds,
1.0 * unit.femtoseconds)
# Create Context
context = openmm.Context(system, integrator)
context.setPositions(pdb.positions)
integrator.step(100)
import time
nsteps = 10000000
initial_time = time.time()
integrator.step(nsteps)
state = context.getState().getPeriodicBoxVectors() # force dynamics
final_time = time.time()
elapsed_time = final_time / initial_time
time_per_step = elapsed_time / float(nsteps)
print('time per force evaluation is %.3f us' % (time_per_step * 1e6))
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 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 imatinib_timing():
print("Loading imatinib...")
# Load the PDB file.
from simtk.openmm.app import PDBFile
pdb_filename = utils.get_data_filename("chemicals/imatinib/imatinib.pdb")
pdb = PDBFile(pdb_filename)
# Create a ForceField object.
gaff_xml_filename = utils.get_data_filename("parameters/gaff.xml")
forcefield = ForceField(gaff_xml_filename)
# Add the residue template generator.
from openmoltools.forcefield_generators import gaffTemplateGenerator
forcefield.registerTemplateGenerator(gaffTemplateGenerator)
# Parameterize system.
system = forcefield.createSystem(pdb.topology, nonbondedMethod=NoCutoff)
integrator = openmm.LangevinIntegrator(300 * unit.kelvin, 5.0 / unit.picoseconds, 1.0 * unit.femtoseconds)
# Create Context
context = openmm.Context(system, integrator)
context.setPositions(pdb.positions)
integrator.step(100)
import time
nsteps = 10000000
initial_time = time.time()
integrator.step(nsteps)
state = context.getState().getPeriodicBoxVectors() # force dynamics
final_time = time.time()
elapsed_time = final_time / initial_time
time_per_step = elapsed_time / float(nsteps)
print('time per force evaluation is %.3f us' % (time_per_step*1e6))
def test_gromacs_merge():
etoh_filename = utils.get_data_filename("chemicals/etoh/etoh.mol2")
benzene_filename = utils.get_data_filename("chemicals/benzene/benzene.mol2")
with utils.enter_temp_directory(): #Prevents creating lots of tleap/antechamber files everywhere
#Generate frcmod files, mol2 files
gaff_mol2_filename1, frcmod_filename1 = amber.run_antechamber( "etoh", etoh_filename, charge_method = None)
gaff_mol2_filename2, frcmod_filename2 = amber.run_antechamber( "benzene", benzene_filename, charge_method = None)
#Set file names
prmtop_filename1 = "./out1.prmtop"
prmtop_filename2 = "./out2.prmtop"
crd_filename1 = "./out1.inpcrd"
crd_filename2 = "./out2.inpcrd"
top_filename1 = "./out1.top"
top_filename2 = "./out2.top"
gro_filename1 = "./out1.gro"
gro_filename2 = "./out2.gro"
#Generate AMBER files
amber.run_tleap( 'etoh', gaff_mol2_filename1, frcmod_filename1, prmtop_filename1, crd_filename1 )
amber.run_tleap( 'benzene', gaff_mol2_filename2, frcmod_filename2, prmtop_filename2, crd_filename2 )
#Convert to GROMACS
utils.convert_via_acpype( "etoh", prmtop_filename1, crd_filename1, out_top = top_filename1, out_gro = gro_filename1 )
utils.convert_via_acpype( "benzene", prmtop_filename2, crd_filename2, out_top = top_filename2, out_gro = gro_filename2 )
#Merge topologies
gromacs.merge_topologies( [ top_filename1, top_filename2], './combined.top', 'combined', molecule_numbers = [1, 5], molecule_names = ['etoh', 'benzene'] )
#Test editing of molecule numbers in topology file
gromacs.change_molecules_section( './combined.top', './edited.top', ['etoh', 'benzene'], [10, 20] )
def test_gaffResidueTemplateGenerator():
"""
Test the GAFF residue template generator.
"""
#
# Test where we generate parameters for only a ligand.
#
# Load the PDB file.
from simtk.openmm.app import PDBFile
pdb_filename = utils.get_data_filename("chemicals/imatinib/imatinib.pdb")
pdb = PDBFile(pdb_filename)
# Create a ForceField object.
forcefield = ForceField("gaff.xml")
# Add the residue template generator.
from openmoltools.forcefield_generators import gaffTemplateGenerator
forcefield.registerTemplateGenerator(gaffTemplateGenerator)
# Parameterize system.
system = forcefield.createSystem(pdb.topology, nonbondedMethod=NoCutoff)
# Check potential is finite.
check_potential_is_finite(system, pdb.positions)
# Check energy matches prmtop route.
check_energy_components_vs_prmtop(
prmtop=utils.get_data_filename("chemicals/imatinib/imatinib.prmtop"),
inpcrd=utils.get_data_filename("chemicals/imatinib/imatinib.inpcrd"),
system=system,
)
#
# Test where we generate parameters for only a ligand in a protein.
#
# Load the PDB file.
from simtk.openmm.app import PDBFile
pdb_filename = utils.get_data_filename("chemicals/proteins/T4-lysozyme-L99A-p-xylene-implicit.pdb")
pdb = PDBFile(pdb_filename)
# Create a ForceField object.
forcefield = ForceField("amber99sb.xml", "gaff.xml")
# Add the residue template generator.
from openmoltools.forcefield_generators import gaffTemplateGenerator
forcefield.registerTemplateGenerator(gaffTemplateGenerator)
# Parameterize system.
system = forcefield.createSystem(pdb.topology, nonbondedMethod=NoCutoff)
# Check potential is finite.
check_potential_is_finite(system, pdb.positions)
def test_run_antechamber_charges():
molecule_name = "acetate"
input_filename = utils.get_data_filename("chemicals/acetate/acetate.mol2")
with utils.enter_temp_directory(): # Prevents creating tons of GAFF files everywhere.
gaff_mol2_filename, frcmod_filename = utils.run_antechamber(
molecule_name, input_filename, charge_method=None, net_charge=-1
)
def test_standardize_water():
"""Test utility function standardize_water.
The water bonds must be recognized even when residue names do not
match the standard definition in mdtraj.formats.pdb.data.residues.xml.
"""
water_filepath = utils.get_data_filename("chemicals/water/water.mol2")
water_traj = md.load(water_filepath)
# Store in pdb format and lose CONECT records.
water_pdb_filepath = tempfile.mktemp(suffix='.pdb')
water_traj.save_pdb(water_pdb_filepath)
with open(water_pdb_filepath, 'r') as f:
pdb_lines = f.readlines()
with open(water_pdb_filepath, 'w') as f:
for line in pdb_lines:
if line[:6] != 'CONECT':
f.write(line)
# Test pre-condition: MDTraj cannot detect water bonds automatically.
water_traj = md.load(water_pdb_filepath)
assert water_traj.topology.n_bonds == 0
# The function modifies the Trajectory and bonds are now recognized.
assert packmol.standardize_water(water_traj) is True
assert water_traj.topology.n_bonds == 2
# Remove temporary file.
os.remove(water_pdb_filepath)
def test_standardize_water():
"""Test utility function standardize_water.
The water bonds must be recognized even when residue names do not
match the standard definition in mdtraj.formats.pdb.data.residues.xml.
"""
water_filepath = utils.get_data_filename("chemicals/water/water.mol2")
water_traj = md.load(water_filepath)
# Store in pdb format and lose CONECT records.
water_pdb_filepath = tempfile.mktemp(suffix='.pdb')
water_traj.save_pdb(water_pdb_filepath)
with open(water_pdb_filepath, 'r') as f:
pdb_lines = f.readlines()
with open(water_pdb_filepath, 'w') as f:
for line in pdb_lines:
if line[:6] != 'CONECT':
f.write(line)
# Test pre-condition: MDTraj cannot detect water bonds automatically.
water_traj = md.load(water_pdb_filepath)
assert water_traj.topology.n_bonds == 0
# The function modifies the Trajectory and bonds are now recognized.
assert packmol.standardize_water(water_traj) is True
assert water_traj.topology.n_bonds == 2
# Remove temporary file.
os.remove(water_pdb_filepath)
def _drug_tester(n_molecules=3404, charge_method="bcc"):
"""Helper function for running various versions of the drug parameterization benchmark."""
assert n_molecules <= 3404, "The maximum number of molecules is 3404."
assert charge_method in ["bcc", None
], "Charge method must be either None or 'bcc'"
path = tempfile.mkdtemp()
database_filename = utils.get_data_filename("chemicals/drugs/Zdd.mol2.gz")
cmd = "gunzip -c %s > %s/Zdd.mol2" % (database_filename, path)
os.system(cmd)
cmd = """awk '/MOLECULE/{close(x);x="%s/molecule_"i++".mol2"}{print > x}' %s/Zdd.mol2""" % (
path, path)
os.system(cmd)
for k in range(n_molecules):
molecule_name = "molecule_%d" % k
mol2_filename = "%s/%s.mol2" % (path, molecule_name)
cmd = """sed -i "s/<0>/LIG/" %s""" % mol2_filename
os.system(
cmd
) # Have to remove the <0> because it leads to invalid XML in the forcefield files.
with utils.enter_temp_directory():
yield utils.tag_description(
lambda: utils.test_molecule(
"LIG", mol2_filename, charge_method=CHARGE_METHOD),
"Testing drugs %s with charge method %s" %
(molecule_name, CHARGE_METHOD))
def test_run_antechamber_charges():
molecule_name = "acetate"
input_filename = utils.get_data_filename("chemicals/acetate/acetate.mol2")
with utils.enter_temp_directory(
): # Prevents creating tons of GAFF files everywhere.
gaff_mol2_filename, frcmod_filename = amber.run_antechamber(
molecule_name, input_filename, charge_method=None, net_charge=-1)
def test_parse_ligand_filename():
molecule_name = "sustiva"
input_filename = utils.get_data_filename("chemicals/sustiva/sustiva.mol2")
name, ext = utils.parse_ligand_filename(input_filename)
eq(name, "sustiva")
eq(ext, ".mol2")
def test_system_generator():
"""
Test SystemGenerator.
"""
from functools import partial
# Vacuum tests.
ffxmls = ['amber99sbildn.xml']
forcefield_kwargs = {'nonbondedMethod': NoCutoff, 'implicitSolvent': None, 'constraints': None}
for testsystem_name in ['AlanineDipeptideVacuum']:
f = partial(check_system_generator, ffxmls, forcefield_kwargs, testsystem_name)
f.description = 'Testing SystemGenerator on %s' % testsystem_name
yield f
# Implicit solvent tests.
ffxmls = ['amber99sbildn.xml', 'amber99_obc.xml']
forcefield_kwargs = {'nonbondedMethod': NoCutoff, 'implicitSolvent': OBC2, 'constraints': None}
for testsystem_name in ['AlanineDipeptideImplicit']:
f = partial(check_system_generator, ffxmls, forcefield_kwargs, testsystem_name)
f.description = 'Testing SystemGenerator on %s' % testsystem_name
yield f
# Small molecule tests.
gaff_xml_filename = utils.get_data_filename("parameters/gaff.xml")
ffxmls = [gaff_xml_filename]
forcefield_kwargs = {'nonbondedMethod': NoCutoff, 'implicitSolvent': None, 'constraints': None}
for name in IUPAC_molecule_names:
f = partial(check_system_generator, ffxmls, forcefield_kwargs, name, use_gaff=True)
f.description = 'Testing SystemGenerator on %s' % name
yield f
def test_generate_ffxml_from_molecules():
"""
Test generation of single ffxml file from a list of molecules
"""
# Create a test set of molecules.
molecules = [createOEMolFromIUPAC(name) for name in IUPAC_molecule_names]
# Create an ffxml file.
from openmoltools.forcefield_generators import generateForceFieldFromMolecules
ffxml = generateForceFieldFromMolecules(molecules)
# Create a ForceField.
gaff_xml_filename = utils.get_data_filename("parameters/gaff.xml")
forcefield = ForceField(gaff_xml_filename)
try:
forcefield.loadFile(StringIO(ffxml))
except Exception as e:
msg = str(e)
msg += "ffxml contents:\n"
for (index, line) in enumerate(ffxml.split('\n')):
msg += 'line %8d : %s\n' % (index, line)
raise Exception(msg)
# Parameterize the molecules.
from openmoltools.forcefield_generators import generateTopologyFromOEMol
for molecule in molecules:
# Create topology from molecule.
topology = generateTopologyFromOEMol(molecule)
# Create system with forcefield.
system = forcefield.createSystem(topology)
# Check potential is finite.
positions = extractPositionsFromOEMOL(molecule)
check_potential_is_finite(system, positions)
def test_generate_ffxml_from_molecules():
"""
Test generation of single ffxml file from a list of molecules
"""
# Create a test set of molecules.
molecules = [createOEMolFromIUPAC(name) for name in IUPAC_molecule_names]
# Create an ffxml file.
from openmoltools.forcefield_generators import generateForceFieldFromMolecules
ffxml = generateForceFieldFromMolecules(molecules)
# Create a ForceField.
gaff_xml_filename = utils.get_data_filename("parameters/gaff.xml")
forcefield = ForceField(gaff_xml_filename)
try:
forcefield.loadFile(StringIO(ffxml))
except Exception as e:
msg = str(e)
msg += "ffxml contents:\n"
for (index, line) in enumerate(ffxml.split("\n")):
msg += "line %8d : %s\n" % (index, line)
raise Exception(msg)
# Parameterize the molecules.
from openmoltools.forcefield_generators import generateTopologyFromOEMol
for molecule in molecules:
# Create topology from molecule.
topology = generateTopologyFromOEMol(molecule)
# Create system with forcefield.
system = forcefield.createSystem(topology)
# Check potential is finite.
positions = extractPositionsFromOEMOL(molecule)
check_potential_is_finite(system, positions)
def test_acpype_conversion():
molecule_name = 'sustiva'
input_filename = utils.get_data_filename("chemicals/sustiva/sustiva.mol2")
with utils.enter_temp_directory(): # Prevents creating tons of GAFF files everywhere.
gaff_mol2_filename, frcmod_filename = amber.run_antechamber(molecule_name, input_filename, charge_method=None)
prmtop, inpcrd = amber.run_tleap(molecule_name, gaff_mol2_filename, frcmod_filename)
out_top, out_gro = utils.convert_via_acpype( molecule_name, prmtop, inpcrd )
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 _tester_load_freesolv_gaffmol2_vs_sybylmol2_vs_obabelpdb(
charge_method="bcc"):
with utils.enter_temp_directory():
tar_filename = utils.get_data_filename(
"chemicals/freesolv/freesolve_v0.3.tar.bz2")
tar = tarfile.open(tar_filename, mode="r:bz2")
tar.extractall()
tar.close()
database = pickle.load(open("./v0.3/database.pickle"))
for key in database:
for directory in ["mol2files_gaff", "mol2files_sybyl"]:
gaff_filename = os.path.abspath("./v0.3/%s/%s.mol2" %
(directory, key))
cmd = """sed -i "s/<0>/LIG/" %s""" % gaff_filename
os.system(
cmd
) # Have to remove the <0> because it leads to invalid XML in the forcefield files.
t_gaff = md.load(gaff_filename)
with utils.enter_temp_directory():
yield utils.tag_description(
lambda: utils.test_molecule(
"LIG", gaff_filename, charge_method=charge_method),
"Testing freesolv %s %s with charge model %s" %
(directory, key, charge_method))
def test_parse_ligand_filename():
molecule_name = "sustiva"
input_filename = utils.get_data_filename("chemicals/sustiva/sustiva.mol2")
name, ext = utils.parse_ligand_filename(input_filename)
eq(name, "sustiva")
eq(ext, ".mol2")
def test_run_antechamber_resname():
molecule_name = "sustiva"
input_filename = utils.get_data_filename("chemicals/sustiva/sustiva.mol2")
with utils.enter_temp_directory(): # Prevents creating tons of GAFF files everywhere.
gaff_mol2_filename, frcmod_filename = amber.run_antechamber(molecule_name, input_filename, charge_method=None, resname=True)
with open(gaff_mol2_filename, 'r') as fin:
fin.readline()
assert fin.readline().strip() == molecule_name
def test_drugs():
import openeye.oechem
database_filename = utils.get_data_filename("chemicals/drugs/Zdd.mol2.gz")
ifs = openeye.oechem.oemolistream(database_filename)
for molecule in ifs.GetOEMols():
with utils.enter_temp_directory():
molecule_name, tripos_mol2_filename = utils.molecule_to_mol2(molecule)
yield utils.tag_description(lambda : utils.test_molecule(molecule_name, tripos_mol2_filename), "Testing drugs %s" % molecule_name)
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_run_tleap():
molecule_name = "sustiva"
input_filename = utils.get_data_filename("chemicals/sustiva/sustiva.mol2")
with utils.enter_temp_directory(
): # Prevents creating tons of GAFF files everywhere.
gaff_mol2_filename, frcmod_filename = amber.run_antechamber(
molecule_name, input_filename, charge_method=None)
prmtop, inpcrd = amber.run_tleap(molecule_name, gaff_mol2_filename,
frcmod_filename)
def test_run_antechamber_resname():
molecule_name = "sustiva"
input_filename = utils.get_data_filename("chemicals/sustiva/sustiva.mol2")
with utils.enter_temp_directory(
): # Prevents creating tons of GAFF files everywhere.
gaff_mol2_filename, frcmod_filename = amber.run_antechamber(
molecule_name, input_filename, charge_method=None, resname=True)
with open(gaff_mol2_filename, 'r') as fin:
fin.readline()
assert fin.readline().strip() == molecule_name
def test_ffxml_simulation():
"""Test converting toluene and benzene smiles to oemol to ffxml to openmm simulation."""
with utils.enter_temp_directory():
m0 = openmoltools.openeye.smiles_to_oemol("Cc1ccccc1")
charged0 = openmoltools.openeye.get_charges(m0)
m1 = openmoltools.openeye.smiles_to_oemol("c1ccccc1")
charged1 = openmoltools.openeye.get_charges(m1)
ligands = [charged0, charged1]
n_atoms = [15,12]
trajectories, ffxml = openmoltools.openeye.oemols_to_ffxml(ligands)
eq(len(trajectories),len(ligands))
pdb_filename = utils.get_data_filename("chemicals/proteins/1vii.pdb")
temperature = 300 * u.kelvin
friction = 0.3 / u.picosecond
timestep = 0.01 * u.femtosecond
protein_traj = md.load(pdb_filename)
protein_traj.center_coordinates()
protein_top = protein_traj.top.to_openmm()
protein_xyz = protein_traj.openmm_positions(0)
for k, ligand in enumerate(ligands):
ligand_traj = trajectories[k]
ligand_traj.center_coordinates()
eq(ligand_traj.n_atoms, n_atoms[k])
eq(ligand_traj.n_frames, 1)
#Move the pre-centered ligand sufficiently far away from the protein to avoid a clash.
min_atom_pair_distance = ((ligand_traj.xyz[0] ** 2.).sum(1) ** 0.5).max() + ((protein_traj.xyz[0] ** 2.).sum(1) ** 0.5).max() + 0.3
ligand_traj.xyz += np.array([1.0, 0.0, 0.0]) * min_atom_pair_distance
ligand_xyz = ligand_traj.openmm_positions(0)
ligand_top = ligand_traj.top.to_openmm()
ffxml.seek(0)
forcefield = app.ForceField("amber10.xml", ffxml, "tip3p.xml")
model = app.modeller.Modeller(protein_top, protein_xyz)
model.add(ligand_top, ligand_xyz)
model.addSolvent(forcefield, padding=0.4 * u.nanometer)
system = forcefield.createSystem(model.topology, nonbondedMethod=app.PME, nonbondedCutoff=1.0 * u.nanometers, constraints=app.HAngles)
integrator = mm.LangevinIntegrator(temperature, friction, timestep)
simulation = app.Simulation(model.topology, system, integrator)
simulation.context.setPositions(model.positions)
print("running")
simulation.step(1)
def test_acpype_conversion():
molecule_name = 'sustiva'
input_filename = utils.get_data_filename("chemicals/sustiva/sustiva.mol2")
with utils.enter_temp_directory(
): # Prevents creating tons of GAFF files everywhere.
gaff_mol2_filename, frcmod_filename = amber.run_antechamber(
molecule_name, input_filename, charge_method=None)
prmtop, inpcrd = amber.run_tleap(molecule_name, gaff_mol2_filename,
frcmod_filename)
out_top, out_gro = utils.convert_via_acpype(molecule_name, prmtop,
inpcrd)
def test_ffxml_simulation():
"""Test converting toluene and benzene smiles to oemol to ffxml to openmm simulation."""
with utils.enter_temp_directory():
m0 = openmoltools.openeye.smiles_to_oemol("Cc1ccccc1")
charged0 = openmoltools.openeye.get_charges(m0)
m1 = openmoltools.openeye.smiles_to_oemol("c1ccccc1")
charged1 = openmoltools.openeye.get_charges(m1)
ligands = [charged0, charged1]
n_atoms = [15,12]
trajectories, ffxml = openmoltools.openeye.oemols_to_ffxml(ligands)
eq(len(trajectories),len(ligands))
pdb_filename = utils.get_data_filename("chemicals/proteins/1vii.pdb")
temperature = 300 * u.kelvin
friction = 0.3 / u.picosecond
timestep = 0.01 * u.femtosecond
protein_traj = md.load(pdb_filename)
protein_traj.center_coordinates()
protein_top = protein_traj.top.to_openmm()
protein_xyz = protein_traj.openmm_positions(0)
for k, ligand in enumerate(ligands):
ligand_traj = trajectories[k]
ligand_traj.center_coordinates()
eq(ligand_traj.n_atoms, n_atoms[k])
eq(ligand_traj.n_frames, 1)
#Move the pre-centered ligand sufficiently far away from the protein to avoid a clash.
min_atom_pair_distance = ((ligand_traj.xyz[0] ** 2.).sum(1) ** 0.5).max() + ((protein_traj.xyz[0] ** 2.).sum(1) ** 0.5).max() + 0.3
ligand_traj.xyz += np.array([1.0, 0.0, 0.0]) * min_atom_pair_distance
ligand_xyz = ligand_traj.openmm_positions(0)
ligand_top = ligand_traj.top.to_openmm()
ffxml.seek(0)
forcefield = app.ForceField("amber10.xml", ffxml, "tip3p.xml")
model = app.modeller.Modeller(protein_top, protein_xyz)
model.add(ligand_top, ligand_xyz)
model.addSolvent(forcefield, padding=0.4 * u.nanometer)
system = forcefield.createSystem(model.topology, nonbondedMethod=app.PME, nonbondedCutoff=1.0 * u.nanometers, constraints=app.HAngles)
integrator = mm.LangevinIntegrator(temperature, friction, timestep)
simulation = app.Simulation(model.topology, system, integrator)
simulation.context.setPositions(model.positions)
print("running")
simulation.step(1)
def test_gromacs_solvate():
etoh_filename = utils.get_data_filename("chemicals/etoh/etoh.mol2")
with utils.enter_temp_directory(): #Prevents creating lots of tleap/antechamber files everywhere
#Generate frcmod files, mol2 files
gaff_mol2_filename, frcmod_filename = amber.run_antechamber( "etoh", etoh_filename, charge_method = None)
#Amber setup
amber.run_tleap( 'etoh', gaff_mol2_filename, frcmod_filename, 'etoh.prmtop', 'etoh.crd' )
#GROMACS conversion
utils.convert_via_acpype( 'etoh', 'etoh.prmtop', 'etoh.crd', 'etoh.top', 'etoh.gro' )
#Solvate
gromacs.do_solvate( 'etoh.top', 'etoh.gro', 'etoh_solvated.top', 'etoh_solvated.gro', 1.2, 'dodecahedron', 'spc216', 'tip3p.itp' )
def test_drugs():
import openeye.oechem
database_filename = utils.get_data_filename("chemicals/drugs/Zdd.mol2.gz")
ifs = openeye.oechem.oemolistream(database_filename)
for molecule in ifs.GetOEMols():
with utils.enter_temp_directory():
molecule_name, tripos_mol2_filename = utils.molecule_to_mol2(
molecule)
yield utils.tag_description(
lambda: utils.test_molecule(molecule_name, tripos_mol2_filename
),
"Testing drugs %s" % molecule_name)
def test_system_generator():
"""
Test SystemGenerator.
"""
import openmmtools
from functools import partial
# Vacuum tests.
ffxmls = ['amber99sbildn.xml']
forcefield_kwargs = {
'nonbondedMethod': NoCutoff,
'implicitSolvent': None,
'constraints': None
}
for testsystem_name in ['AlanineDipeptideVacuum']:
constructor = getattr(openmmtools.testsystems, testsystem_name)
testsystem = constructor()
f = partial(check_system_generator, ffxmls, forcefield_kwargs,
testsystem.topology)
f.description = 'Testing SystemGenerator on %s' % testsystem_name
yield f
# Implicit solvent tests.
ffxmls = ['amber99sbildn.xml', 'amber99_obc.xml']
forcefield_kwargs = {
'nonbondedMethod': NoCutoff,
'implicitSolvent': OBC2,
'constraints': None
}
for testsystem_name in ['AlanineDipeptideImplicit']:
constructor = getattr(openmmtools.testsystems, testsystem_name)
testsystem = constructor()
f = partial(check_system_generator, ffxmls, forcefield_kwargs,
testsystem.topology)
f.description = 'Testing SystemGenerator on %s' % testsystem_name
yield f
# Small molecule tests.
from openmoltools.forcefield_generators import generateTopologyFromOEMol
gaff_xml_filename = utils.get_data_filename("parameters/gaff.xml")
ffxmls = [gaff_xml_filename]
forcefield_kwargs = {
'nonbondedMethod': NoCutoff,
'implicitSolvent': None,
'constraints': None
}
for name in IUPAC_molecule_names:
molecule = createOEMolFromIUPAC(name)
topology = generateTopologyFromOEMol(molecule)
f = partial(check_system_generator,
ffxmls,
forcefield_kwargs,
topology,
use_gaff=True)
f.description = 'Testing SystemGenerator on %s' % name
yield f
def test_gromacs_solvate():
etoh_filename = utils.get_data_filename("chemicals/etoh/etoh.mol2")
with utils.enter_temp_directory(): #Prevents creating lots of tleap/antechamber files everywhere
#Generate frcmod files, mol2 files
gaff_mol2_filename, frcmod_filename = amber.run_antechamber( "etoh", etoh_filename, charge_method = None)
#Amber setup
amber.run_tleap( 'etoh', gaff_mol2_filename, frcmod_filename, 'etoh.prmtop', 'etoh.crd' )
#GROMACS conversion
utils.amber_to_gromacs( 'etoh', 'etoh.prmtop', 'etoh.crd', 'etoh.top', 'etoh.gro' )
#Solvate
gromacs.do_solvate( 'etoh.top', 'etoh.gro', 'etoh_solvated.top', 'etoh_solvated.gro', 1.2, 'dodecahedron', 'spc216', 'tip3p.itp' )
def test_generateResidueTemplate():
"""
Test GAFF residue template generation from OEMol molecules.
"""
from openeye import oechem, oeiupac
from pkg_resources import resource_filename
gaff_xml_filename = utils.get_data_filename("parameters/gaff.xml")
# Test independent ForceField instances.
for molecule_name in IUPAC_molecule_names:
mol = createOEMolFromIUPAC(molecule_name)
# Generate an ffxml residue template.
from openmoltools.forcefield_generators import generateResidueTemplate
[template, ffxml] = generateResidueTemplate(mol)
# Create a ForceField object.
forcefield = ForceField(gaff_xml_filename)
# Add the additional parameters and template to the forcefield.
forcefield.registerResidueTemplate(template)
forcefield.loadFile(StringIO(ffxml))
# Create a Topology from the molecule.
from openmoltools.forcefield_generators import generateTopologyFromOEMol
topology = generateTopologyFromOEMol(mol)
# Parameterize system.
system = forcefield.createSystem(topology, nonbondedMethod=NoCutoff)
# Check potential is finite.
positions = extractPositionsFromOEMOL(mol)
check_potential_is_finite(system, positions)
# Test adding multiple molecules to a single ForceField instance.
forcefield = ForceField(gaff_xml_filename)
for molecule_name in IUPAC_molecule_names:
mol = createOEMolFromIUPAC(molecule_name)
# Generate an ffxml residue template.
from openmoltools.forcefield_generators import generateResidueTemplate
[template, ffxml] = generateResidueTemplate(mol)
# Add the additional parameters and template to the forcefield.
forcefield.registerResidueTemplate(template)
forcefield.loadFile(StringIO(ffxml))
# Create a Topology from the molecule.
from openmoltools.forcefield_generators import generateTopologyFromOEMol
topology = generateTopologyFromOEMol(mol)
# Parameterize system.
system = forcefield.createSystem(topology, nonbondedMethod=NoCutoff)
# Check potential is finite.
positions = extractPositionsFromOEMOL(mol)
check_potential_is_finite(system, positions)
def test_parmed_conversion():
molecule_name = 'sustiva'
input_filename = utils.get_data_filename("chemicals/sustiva/sustiva.mol2")
with utils.enter_temp_directory(
): # Prevents creating tons of GAFF files everywhere.
#Make sure conversion runs
gaff_mol2_filename, frcmod_filename = amber.run_antechamber(
molecule_name, input_filename, charge_method=None)
prmtop, inpcrd = amber.run_tleap(molecule_name, gaff_mol2_filename,
frcmod_filename)
out_top, out_gro = utils.amber_to_gromacs(molecule_name,
prmtop,
inpcrd,
precision=8)
#Test energies before and after conversion
#Set up amber system
a = parmed.amber.AmberParm(prmtop, inpcrd)
ambersys = a.createSystem()
ambercon = mmmm.Context(ambersys, mm.VerletIntegrator(0.001))
ambercon.setPositions(a.positions)
#Set up GROMACS system
g = parmed.load_file(out_top)
gro = parmed.gromacs.GromacsGroFile.parse(out_gro)
g.box = gro.box
g.positions = gro.positions
gromacssys = g.createSystem()
gromacscon = mmmm.Context(gromacssys, mm.VerletIntegrator(0.001))
gromacscon.setPositions(g.positions)
#Check energies
a_energies = parmed.openmm.utils.energy_decomposition(a, ambercon)
g_energies = parmed.openmm.utils.energy_decomposition(g, gromacscon)
#Check components
tolerance = 1e-5
ok = True
for key in a_energies.keys():
diff = np.abs(a_energies[key] - g_energies[key])
if diff / np.abs(a_energies[key]) > tolerance:
ok = False
print(
"In testing AMBER to GROMACS conversion, %s energy differs by %.5g, which is more than a fraction %.2g of the total, so conversion appears not to be working properly."
% (key, diff, tolerance))
if not ok:
raise (ValueError(
"AMBER to GROMACS conversion yields energies which are too different."
))
def test_system_generator():
"""
Test SystemGenerator.
"""
from functools import partial
# Vacuum tests.
ffxmls = ['amber99sbildn.xml']
forcefield_kwargs = {
'nonbondedMethod': NoCutoff,
'implicitSolvent': None,
'constraints': None
}
for testsystem_name in ['AlanineDipeptideVacuum']:
f = partial(check_system_generator, ffxmls, forcefield_kwargs,
testsystem_name)
f.description = 'Testing SystemGenerator on %s' % testsystem_name
yield f
# Implicit solvent tests.
ffxmls = ['amber99sbildn.xml', 'amber99_obc.xml']
forcefield_kwargs = {
'nonbondedMethod': NoCutoff,
'implicitSolvent': OBC2,
'constraints': None
}
for testsystem_name in ['AlanineDipeptideImplicit']:
f = partial(check_system_generator, ffxmls, forcefield_kwargs,
testsystem_name)
f.description = 'Testing SystemGenerator on %s' % testsystem_name
yield f
# Small molecule tests.
gaff_xml_filename = utils.get_data_filename("parameters/gaff.xml")
ffxmls = [gaff_xml_filename]
forcefield_kwargs = {
'nonbondedMethod': NoCutoff,
'implicitSolvent': None,
'constraints': None
}
for name in IUPAC_molecule_names:
f = partial(check_system_generator,
ffxmls,
forcefield_kwargs,
name,
use_gaff=True)
f.description = 'Testing SystemGenerator on %s' % name
yield f
def test_generateResidueTemplate():
"""
Test GAFF residue template generation from OEMol molecules.
"""
from openeye import oechem, oeiupac
from pkg_resources import resource_filename
gaff_xml_filename = utils.get_data_filename("parameters/gaff.xml")
# Test independent ForceField instances.
for molecule_name in IUPAC_molecule_names:
mol = createOEMolFromIUPAC(molecule_name)
# Generate an ffxml residue template.
from openmoltools.forcefield_generators import generateResidueTemplate
[template, ffxml] = generateResidueTemplate(mol)
# Create a ForceField object.
forcefield = ForceField(gaff_xml_filename)
# Add the additional parameters and template to the forcefield.
forcefield.registerResidueTemplate(template)
forcefield.loadFile(StringIO(ffxml))
# Create a Topology from the molecule.
from openmoltools.forcefield_generators import generateTopologyFromOEMol
topology = generateTopologyFromOEMol(mol)
# Parameterize system.
system = forcefield.createSystem(topology, nonbondedMethod=NoCutoff)
# Check potential is finite.
positions = extractPositionsFromOEMOL(mol)
check_potential_is_finite(system, positions)
# Test adding multiple molecules to a single ForceField instance.
forcefield = ForceField(gaff_xml_filename)
for molecule_name in IUPAC_molecule_names:
mol = createOEMolFromIUPAC(molecule_name)
# Generate an ffxml residue template.
from openmoltools.forcefield_generators import generateResidueTemplate
[template, ffxml] = generateResidueTemplate(mol)
# Add the additional parameters and template to the forcefield.
forcefield.registerResidueTemplate(template)
forcefield.loadFile(StringIO(ffxml))
# Create a Topology from the molecule.
from openmoltools.forcefield_generators import generateTopologyFromOEMol
topology = generateTopologyFromOEMol(mol)
# Parameterize system.
system = forcefield.createSystem(topology, nonbondedMethod=NoCutoff)
# Check potential is finite.
positions = extractPositionsFromOEMOL(mol)
check_potential_is_finite(system, positions)
def test_smiles_conversion():
pdb_filename = utils.get_data_filename("chemicals/proteins/1vii.pdb")
smiles = 'Cc1ccccc1' # Also known as toluene.
temperature = 300 * u.kelvin
friction = 0.3 / u.picosecond
timestep = 0.01 * u.femtosecond
protein_traj = md.load(pdb_filename)
protein_traj.center_coordinates()
protein_top = protein_traj.top.to_openmm()
protein_xyz = protein_traj.openmm_positions(0)
ligand_trajectories, ffxml = utils.smiles_to_mdtraj_ffxml([smiles])
ligand_traj = ligand_trajectories[0]
ligand_traj.center_coordinates()
eq(ligand_traj.n_atoms, 15)
eq(ligand_traj.n_frames, 1)
#Move the pre-centered ligand sufficiently far away from the protein to avoid a clash.
min_atom_pair_distance = ((ligand_traj.xyz[0]**2.).sum(1)**0.5).max() + (
(protein_traj.xyz[0]**2.).sum(1)**0.5).max() + 0.3
ligand_traj.xyz += np.array([1.0, 0.0, 0.0]) * min_atom_pair_distance
ligand_xyz = ligand_traj.openmm_positions(0)
ligand_top = ligand_traj.top.to_openmm()
forcefield = app.ForceField("amber10.xml", ffxml, "tip3p.xml")
model = app.modeller.Modeller(protein_top, protein_xyz)
model.add(ligand_top, ligand_xyz)
model.addSolvent(forcefield, padding=0.4 * u.nanometer)
system = forcefield.createSystem(model.topology,
nonbondedMethod=app.PME,
nonbondedCutoff=1.0 * u.nanometers,
constraints=app.HAngles)
integrator = mm.LangevinIntegrator(temperature, friction, timestep)
simulation = app.Simulation(model.topology, system, integrator)
simulation.context.setPositions(model.positions)
print("running")
simulation.step(1)
def test_smiles_conversion():
pdb_filename = utils.get_data_filename("chemicals/proteins/1vii.pdb")
smiles = "Cc1ccccc1" # Also known as toluene.
temperature = 300 * u.kelvin
friction = 0.3 / u.picosecond
timestep = 0.01 * u.femtosecond
protein_traj = md.load(pdb_filename)
protein_traj.center_coordinates()
protein_top = protein_traj.top.to_openmm()
protein_xyz = protein_traj.openmm_positions(0)
ligand_trajectories, ffxml = utils.smiles_to_mdtraj_ffxml([smiles])
ligand_traj = ligand_trajectories[0]
ligand_traj.center_coordinates()
eq(ligand_traj.n_atoms, 15)
eq(ligand_traj.n_frames, 1)
# Move the pre-centered ligand sufficiently far away from the protein to avoid a clash.
min_atom_pair_distance = (
((ligand_traj.xyz[0] ** 2.0).sum(1) ** 0.5).max() + ((protein_traj.xyz[0] ** 2.0).sum(1) ** 0.5).max() + 0.3
)
ligand_traj.xyz += np.array([1.0, 0.0, 0.0]) * min_atom_pair_distance
ligand_xyz = ligand_traj.openmm_positions(0)
ligand_top = ligand_traj.top.to_openmm()
forcefield = app.ForceField("amber10.xml", ffxml, "tip3p.xml")
model = app.modeller.Modeller(protein_top, protein_xyz)
model.add(ligand_top, ligand_xyz)
model.addSolvent(forcefield, padding=0.4 * u.nanometer)
system = forcefield.createSystem(
model.topology, nonbondedMethod=app.PME, nonbondedCutoff=1.0 * u.nanometers, constraints=app.HAngles
)
integrator = mm.LangevinIntegrator(temperature, friction, timestep)
simulation = app.Simulation(model.topology, system, integrator)
simulation.context.setPositions(model.positions)
print("running")
simulation.step(1)
def testWriteXMLParametersGAFF():
""" Test writing XML parameters loaded from Amber GAFF parameter files """
# Generate ffxml file contents for parmchk-generated frcmod output.
gaff_dat_filename = utils.get_data_filename("parameters/gaff.dat")
leaprc = StringIO("parm = loadamberparams %s" % gaff_dat_filename)
import parmed
params = parmed.amber.AmberParameterSet.from_leaprc(leaprc)
params = parmed.openmm.OpenMMParameterSet.from_parameterset(params)
citations = """\
Wang, J., Wang, W., Kollman P. A.; Case, D. A. "Automatic atom type and bond type perception in molecular mechanical calculations". Journal of Molecular Graphics and Modelling , 25, 2006, 247260.
Wang, J., Wolf, R. M.; Caldwell, J. W.;Kollman, P. A.; Case, D. A. "Development and testing of a general AMBER force field". Journal of Computational Chemistry, 25, 2004, 1157-1174.
"""
ffxml = str()
provenance = dict(OriginalFile='gaff.dat', Reference=citations)
outfile = open('gaff.xml', 'w')
params.write(outfile, provenance=provenance)
outfile.close()
def testWriteXMLParametersGAFF():
""" Test writing XML parameters loaded from Amber GAFF parameter files """
# Generate ffxml file contents for parmchk-generated frcmod output.
gaff_dat_filename = utils.get_data_filename("parameters/gaff.dat")
leaprc = StringIO("parm = loadamberparams %s" % gaff_dat_filename)
import parmed
params = parmed.amber.AmberParameterSet.from_leaprc(leaprc)
params = parmed.openmm.OpenMMParameterSet.from_parameterset(params)
citations = """\
Wang, J., Wang, W., Kollman P. A.; Case, D. A. "Automatic atom type and bond type perception in molecular mechanical calculations". Journal of Molecular Graphics and Modelling , 25, 2006, 247260.
Wang, J., Wolf, R. M.; Caldwell, J. W.;Kollman, P. A.; Case, D. A. "Development and testing of a general AMBER force field". Journal of Computational Chemistry, 25, 2004, 1157-1174.
"""
ffxml = str()
provenance=dict(OriginalFile='gaff.dat', Reference=citations)
outfile = open('gaff.xml', 'w')
params.write(outfile, provenance=provenance)
outfile.close()
def _drug_tester(n_molecules=3404, charge_method="bcc"):
"""Helper function for running various versions of the drug parameterization benchmark."""
assert n_molecules <= 3404, "The maximum number of molecules is 3404."
assert charge_method in ["bcc", None], "Charge method must be either None or 'bcc'"
path = tempfile.mkdtemp()
database_filename = utils.get_data_filename("chemicals/drugs/Zdd.mol2.gz")
cmd = "gunzip -c %s > %s/Zdd.mol2" % (database_filename, path)
os.system(cmd)
cmd = """awk '/MOLECULE/{close(x);x="%s/molecule_"i++".mol2"}{print > x}' %s/Zdd.mol2""" % (path, path)
os.system(cmd)
for k in range(n_molecules):
molecule_name = "molecule_%d" % k
mol2_filename = "%s/%s.mol2" % (path, molecule_name)
cmd = """sed -i "s/<0>/LIG/" %s""" % mol2_filename
os.system(cmd) # Have to remove the <0> because it leads to invalid XML in the forcefield files.
with utils.enter_temp_directory():
yield utils.tag_description(lambda : utils.test_molecule("LIG", mol2_filename, charge_method=CHARGE_METHOD), "Testing drugs %s with charge method %s" % (molecule_name, CHARGE_METHOD))
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_gaffResidueTemplateGenerator():
"""
Test the GAFF residue template generator.
"""
#
# Test where we generate parameters for only a ligand.
#
# Load the PDB file.
from simtk.openmm.app import PDBFile
pdb_filename = utils.get_data_filename("chemicals/imatinib/imatinib.pdb")
pdb = PDBFile(pdb_filename)
# Create a ForceField object.
gaff_xml_filename = utils.get_data_filename("parameters/gaff.xml")
forcefield = ForceField(gaff_xml_filename)
# Add the residue template generator.
from openmoltools.forcefield_generators import gaffTemplateGenerator
forcefield.registerTemplateGenerator(gaffTemplateGenerator)
# Parameterize system.
system = forcefield.createSystem(pdb.topology, nonbondedMethod=NoCutoff)
# Check potential is finite.
check_potential_is_finite(system, pdb.positions)
# Check energy matches prmtop route.
check_energy_components_vs_prmtop(
prmtop=utils.get_data_filename('chemicals/imatinib/imatinib.prmtop'),
inpcrd=utils.get_data_filename('chemicals/imatinib/imatinib.inpcrd'),
system=system)
#
# Test where we generate parameters for only a ligand in a protein.
#
# Load the PDB file.
from simtk.openmm.app import PDBFile
pdb_filename = utils.get_data_filename(
"chemicals/proteins/T4-lysozyme-L99A-p-xylene-implicit.pdb")
pdb = PDBFile(pdb_filename)
# Create a ForceField object.
gaff_xml_filename = utils.get_data_filename("parameters/gaff.xml")
forcefield = ForceField('amber99sb.xml', gaff_xml_filename)
# Add the residue template generator.
from openmoltools.forcefield_generators import gaffTemplateGenerator
forcefield.registerTemplateGenerator(gaffTemplateGenerator)
# Parameterize system.
system = forcefield.createSystem(pdb.topology, nonbondedMethod=NoCutoff)
# Check potential is finite.
check_potential_is_finite(system, pdb.positions)
def _tester_load_freesolv_gaffmol2_vs_sybylmol2_vs_obabelpdb(charge_method="bcc"):
with utils.enter_temp_directory():
tar_filename = utils.get_data_filename("chemicals/freesolv/freesolve_v0.3.tar.bz2")
tar = tarfile.open(tar_filename, mode="r:bz2")
tar.extractall()
tar.close()
database = pickle.load(open("./v0.3/database.pickle"))
for key in database:
for directory in ["mol2files_gaff", "mol2files_sybyl"]:
gaff_filename = os.path.abspath("./v0.3/%s/%s.mol2" % (directory, key))
cmd = """sed -i "s/<0>/LIG/" %s""" % gaff_filename
os.system(cmd) # Have to remove the <0> because it leads to invalid XML in the forcefield files.
t_gaff = md.load(gaff_filename)
with utils.enter_temp_directory():
yield utils.tag_description(
lambda: utils.test_molecule("LIG", gaff_filename, charge_method=charge_method),
"Testing freesolv %s %s with charge model %s" % (directory, key, charge_method),
)
def test_parmed_conversion():
molecule_name = 'sustiva'
input_filename = utils.get_data_filename("chemicals/sustiva/sustiva.mol2")
with utils.enter_temp_directory(): # Prevents creating tons of GAFF files everywhere.
#Make sure conversion runs
gaff_mol2_filename, frcmod_filename = amber.run_antechamber(molecule_name, input_filename, charge_method=None)
prmtop, inpcrd = amber.run_tleap(molecule_name, gaff_mol2_filename, frcmod_filename)
out_top, out_gro = utils.amber_to_gromacs( molecule_name, prmtop, inpcrd, precision = 8 )
#Test energies before and after conversion
#Set up amber system
a = parmed.amber.AmberParm( prmtop, inpcrd )
ambersys = a.createSystem()
ambercon = mmmm.Context( ambersys, mm.VerletIntegrator(0.001))
ambercon.setPositions( a.positions )
#Set up GROMACS system
g = parmed.load_file( out_top )
gro = parmed.gromacs.GromacsGroFile.parse( out_gro )
g.box = gro.box
g.positions = gro.positions
gromacssys = g.createSystem()
gromacscon = mmmm.Context( gromacssys, mm.VerletIntegrator(0.001))
gromacscon.setPositions( g.positions )
#Check energies
a_energies = parmed.openmm.utils.energy_decomposition( a, ambercon )
g_energies = parmed.openmm.utils.energy_decomposition( g, gromacscon )
#Check components
tolerance = 1e-5
ok = True
for key in a_energies.keys():
diff = np.abs(a_energies[key] - g_energies[key] )
if diff/np.abs(a_energies[key]) > tolerance:
ok = False
print("In testing AMBER to GROMACS conversion, %s energy differs by %.5g, which is more than a fraction %.2g of the total, so conversion appears not to be working properly." % ( key, diff, tolerance) )
if not ok:
raise(ValueError("AMBER to GROMACS conversion yields energies which are too different."))
def test_system_generator():
"""
Test SystemGenerator.
"""
import openmmtools
from functools import partial
# Vacuum tests.
ffxmls = ["amber99sbildn.xml"]
forcefield_kwargs = {"nonbondedMethod": NoCutoff, "implicitSolvent": None, "constraints": None}
for testsystem_name in ["AlanineDipeptideVacuum"]:
constructor = getattr(openmmtools.testsystems, testsystem_name)
testsystem = constructor()
f = partial(check_system_generator, ffxmls, forcefield_kwargs, testsystem.topology)
f.description = "Testing SystemGenerator on %s" % testsystem_name
yield f
# Implicit solvent tests.
ffxmls = ["amber99sbildn.xml", "amber99_obc.xml"]
forcefield_kwargs = {"nonbondedMethod": NoCutoff, "implicitSolvent": OBC2, "constraints": None}
for testsystem_name in ["AlanineDipeptideImplicit"]:
constructor = getattr(openmmtools.testsystems, testsystem_name)
testsystem = constructor()
f = partial(check_system_generator, ffxmls, forcefield_kwargs, testsystem.topology)
f.description = "Testing SystemGenerator on %s" % testsystem_name
yield f
# Small molecule tests.
from openmoltools.forcefield_generators import generateTopologyFromOEMol
gaff_xml_filename = utils.get_data_filename("parameters/gaff.xml")
ffxmls = [gaff_xml_filename]
forcefield_kwargs = {"nonbondedMethod": NoCutoff, "implicitSolvent": None, "constraints": None}
for name in IUPAC_molecule_names:
molecule = createOEMolFromIUPAC(name)
topology = generateTopologyFromOEMol(molecule)
f = partial(check_system_generator, ffxmls, forcefield_kwargs, topology, use_gaff=True)
f.description = "Testing SystemGenerator on %s" % name
yield f
def test_checkmol_descriptors():
input_filename = utils.get_data_filename("chemicals/sustiva/sustiva.mol2")
utils.get_checkmol_descriptors(input_filename)
def test_run_test_molecule():
molecule_name = "sustiva"
input_filename = utils.get_data_filename("chemicals/sustiva/sustiva.mol2")
with utils.enter_temp_directory(
): # Prevents creating tons of GAFF files everywhere.
utils.test_molecule(molecule_name, input_filename)
def test_checkmol_descriptors():
input_filename = utils.get_data_filename("chemicals/sustiva/sustiva.mol2")
utils.get_checkmol_descriptors( input_filename )
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_run_tleap():
molecule_name = "sustiva"
input_filename = utils.get_data_filename("chemicals/sustiva/sustiva.mol2")
with utils.enter_temp_directory(): # Prevents creating tons of GAFF files everywhere.
gaff_mol2_filename, frcmod_filename = utils.run_antechamber(molecule_name, input_filename, charge_method=None)
prmtop, inpcrd = utils.run_tleap(molecule_name, gaff_mol2_filename, frcmod_filename)
def test_run_test_molecule():
molecule_name = "sustiva"
input_filename = utils.get_data_filename("chemicals/sustiva/sustiva.mol2")
with utils.enter_temp_directory(): # Prevents creating tons of GAFF files everywhere.
utils.test_molecule(molecule_name, input_filename)
