def test_run_1a0q_1a07_rsfe_production_with_CHARMM(caplog):
from transformato import (
IntermediateStateFactory,
ProposeMutationRoute,
SystemStructure,
load_config_yaml,
)
from transformato.mutate import perform_mutations
workdir = get_test_output_dir
conf = f"{get_testsystems_dir()}/config/test-1a0q-1a07-rsfe.yaml"
configuration = load_config_yaml(config=conf,
input_dir="data/",
output_dir=workdir)
s1 = SystemStructure(configuration, "structure1")
s2 = SystemStructure(configuration, "structure2")
s1_to_s2 = ProposeMutationRoute(s1, s2)
s1_to_s2.propose_common_core()
s1_to_s2.finish_common_core()
# generate the mutation list for the original
mutation_list = s1_to_s2.generate_mutations_to_common_core_for_mol1()
print(mutation_list.keys())
i = IntermediateStateFactory(
system=s1,
configuration=configuration,
)
perform_mutations(
configuration=configuration,
nr_of_mutation_steps_cc=2,
nr_of_mutation_steps_charge=1,
i=i,
mutation_list=mutation_list,
)
def test_rbfe_mutate_2oj9():
from transformato import (ProposeMutationRoute, SystemStructure,
load_config_yaml)
from ..mutate import mutate_pure_tautomers
conf = f"{get_testsystems_dir()}/config/test-2oj9-tautomer-pair-rbfe.yaml"
configuration = load_config_yaml(
config=conf,
input_dir=get_testsystems_dir(),
output_dir=get_test_output_dir(),
)
s1 = SystemStructure(configuration, "structure1")
s2 = SystemStructure(configuration, "structure2")
s1_to_s2 = ProposeMutationRoute(s1, s2)
s1_to_s2.calculate_common_core()
return (
mutate_pure_tautomers(
s1_to_s2,
s1,
s2,
configuration,
nr_of_bonded_windows=4,
),
configuration,
s1_to_s2,
)
def test_generate_alchemical_path_for_methanol_common_core():
from transformato_testsystems.testsystems import perform_generic_mutation
configuration = load_config_yaml(
config=f"{get_testsystems_dir()}/config/test-methanol-methane-rsfe.yaml",
input_dir=get_testsystems_dir(),
output_dir=get_test_output_dir(),
)
s1 = SystemStructure(configuration, "structure1")
s2 = SystemStructure(configuration, "structure2")
s1_to_s2 = ProposeMutationRoute(s1, s2)
s1_to_s2.calculate_common_core()
mutation_list = s1_to_s2.generate_mutations_to_common_core_for_mol1()
i = IntermediateStateFactory(
system=s1,
configuration=configuration,
)
perform_mutations(
configuration=configuration,
i=i,
mutation_list=mutation_list,
nr_of_mutation_steps_charge=3,
)
assert len(i.output_files) == 11
def test_initialize_systems(caplog):
caplog.set_level(logging.DEBUG)
configuration = load_config_yaml(
config=f"{get_testsystems_dir()}/config/test-toluene-methane-rsfe.yaml",
input_dir=get_testsystems_dir(),
output_dir=get_test_output_dir(),
)
s1 = SystemStructure(configuration, "structure1")
assert int(s1.offset["waterbox"]) == 0
assert int(s1.offset["vacuum"]) == 0
s2 = SystemStructure(configuration, "structure2")
assert int(s2.offset["waterbox"]) == 0
assert int(s2.offset["vacuum"]) == 0
assert "vacuum" in s1.envs and "vacuum" in s2.envs
assert "waterbox" in s1.envs and "waterbox" in s2.envs
configuration = load_config_yaml(
config=
f"{get_testsystems_dir()}/config/test-2oj9-tautomer-pair-rsfe.yaml",
input_dir=get_testsystems_dir(),
output_dir=get_test_output_dir(),
)
s1 = SystemStructure(configuration, "structure1")
assert int(s1.offset["waterbox"]) == 0
assert int(s1.offset["vacuum"]) == 0
s2 = SystemStructure(configuration, "structure2")
assert int(s2.offset["waterbox"]) == 0
assert int(s2.offset["vacuum"]) == 0
def test_lonepairs_in_common_core():
configuration = load_config_yaml(
config=f"{get_testsystems_dir()}/config/tyk2-ejm_45_ejm_42.yaml",
input_dir=get_testsystems_dir(),
output_dir=get_test_output_dir(),
)
s1 = SystemStructure(configuration, "structure1")
s2 = SystemStructure(configuration, "structure2")
s1_to_s2 = ProposeMutationRoute(s1, s2)
s1_to_s2.propose_common_core()
s1_to_s2.finish_common_core()
mutation_list = s1_to_s2.generate_mutations_to_common_core_for_mol1()
i = IntermediateStateFactory(
system=s1,
configuration=configuration,
)
# check for ligand 1
cc_region = s1_to_s2.get_common_core_idx_mol1()
assert (39 in cc_region and 40 in cc_region) == True
perform_mutations(configuration=configuration,
i=i,
mutation_list=mutation_list)
# check for ligand 2
cc_region2 = s1_to_s2.get_common_core_idx_mol2()
assert (35 in cc_region2 and 36 in cc_region2) == True
def test_lonepairs_in_dummy_region():
configuration = load_config_yaml(
config=f"{get_testsystems_dir()}/config/jnk1-17124-18631.yaml",
input_dir=get_testsystems_dir(),
output_dir=get_test_output_dir(),
)
s1 = SystemStructure(configuration, "structure1")
s2 = SystemStructure(configuration, "structure2")
s1_to_s2 = ProposeMutationRoute(s1, s2)
s1_to_s2.propose_common_core()
s1_to_s2.finish_common_core()
mutation_list = s1_to_s2.generate_mutations_to_common_core_for_mol1()
i = IntermediateStateFactory(
system=s1,
configuration=configuration,
)
assert s1_to_s2.dummy_region_cc1.connected_dummy_regions == [
[46, 22],
[45, 44, 43, 26, 25],
]
perform_mutations(configuration=configuration,
i=i,
mutation_list=mutation_list)
mutation_list = s1_to_s2.generate_mutations_to_common_core_for_mol2()
assert s1_to_s2.dummy_region_cc2.connected_dummy_regions == [[39], [40]]
def test_run_1a0q_1a07_rsfe_with_openMM(caplog):
import logging
# Test that TF can handel multiple dummy regions
caplog.set_level(logging.DEBUG)
import warnings
from transformato import (
load_config_yaml,
SystemStructure,
IntermediateStateFactory,
ProposeMutationRoute,
)
from transformato.mutate import perform_mutations
warnings.filterwarnings("ignore", module="parmed")
workdir = get_test_output_dir()
conf = f"{get_testsystems_dir()}/config/test-1a0q-1a07-rsfe.yaml"
configuration = load_config_yaml(
config=conf, input_dir="data/test_systems_mutation", output_dir=workdir
)
s1 = SystemStructure(configuration, "structure1")
s2 = SystemStructure(configuration, "structure2")
s1_to_s2 = ProposeMutationRoute(s1, s2)
s1_to_s2.propose_common_core()
s1_to_s2.finish_common_core()
# generate the mutation list for the original
mutation_list = s1_to_s2.generate_mutations_to_common_core_for_mol1()
print(mutation_list.keys())
i = IntermediateStateFactory(
system=s1,
configuration=configuration,
)
perform_mutations(configuration=configuration, i=i, mutation_list=mutation_list)
run_simulation(i.output_files, engine="openMM")
def test_run_1a0q_1a07_rsfe_with_openMM(caplog):
# Test that TF can handel multiple dummy regions
caplog.set_level(logging.DEBUG)
conf = f"{get_testsystems_dir()}/config/test-1a0q-1a07-rsfe.yaml"
configuration = load_config_yaml(
config=conf, input_dir=get_testsystems_dir(), output_dir=get_test_output_dir()
)
s1 = SystemStructure(configuration, "structure1")
s2 = SystemStructure(configuration, "structure2")
s1_to_s2 = ProposeMutationRoute(s1, s2)
s1_to_s2.propose_common_core()
s1_to_s2.finish_common_core()
# generate the mutation list for the original
mutation_list = s1_to_s2.generate_mutations_to_common_core_for_mol1()
print(mutation_list.keys())
i = IntermediateStateFactory(
system=s1,
configuration=configuration,
)
perform_mutations(configuration=configuration, i=i, mutation_list=mutation_list)
run_simulation(i.output_files, engine="openMM")
# Analysis with mda
ddG_openMM_mda, dddG_mda, f_openMM_mda = postprocessing(
configuration,
name="1a0q",
engine="openMM",
analyze_traj_with="mda",
num_proc=4,
max_snapshots=50,
)
print(f"Free energy difference using mda: {ddG_openMM_mda} +- {dddG_mda} [kT")
# Analysis with mdtraj
ddG_openMM_mtraj, dddG_mtraj, f_openMM_mtraj = postprocessing(
configuration,
name="1a0q",
engine="openMM",
max_snapshots=50,
)
print(
f"Free energy difference using mdtraj: {ddG_openMM_mtraj} +- {dddG_mtraj} [kT"
)
assert np.isclose(ddG_openMM_mda, ddG_openMM_mda, rtol=0.2)
assert np.isclose(dddG_mda, dddG_mda, rtol=0.2)
def test_run_28_1h1q_rbfe_with_openMM():
# Generating output for a run of the CDK2 Ligand System
configuration = load_config_yaml(
config=f"{get_testsystems_dir()}/config/test-28_1h1q_rbfe.yaml",
input_dir=get_testsystems_dir(),
output_dir=get_test_output_dir(),
)
s1 = SystemStructure(configuration, "structure1")
s2 = SystemStructure(configuration, "structure2")
s1_to_s2 = ProposeMutationRoute(s1, s2)
s1_to_s2.propose_common_core()
s1_to_s2.finish_common_core()
mutation_list = s1_to_s2.generate_mutations_to_common_core_for_mol1()
print(mutation_list.keys())
i = IntermediateStateFactory(
system=s1,
configuration=configuration,
)
perform_mutations(
configuration=configuration,
i=i,
mutation_list=mutation_list,
nr_of_mutation_steps_charge=2,
nr_of_mutation_steps_cc=2,
)
run_simulation(i.output_files, engine="charmm")
from transformato.utils import postprocessing
ddG_openMM, dddG, f_openMM = postprocessing(
configuration,
name="cdk2-28",
engine="openMM",
max_snapshots=50,
num_proc=4,
analyze_traj_with="mda",
)
print(f"Free energy difference: {ddG_openMM} +- {dddG} [kT")
def test_generate_alchemical_path_for_1a0q_1a07(caplog):
# Test that TF can handel multiple dummy regions
caplog.set_level(logging.INFO)
conf = f"{get_testsystems_dir()}/config/test-1a0q-1a07-rsfe.yaml"
configuration = load_config_yaml(
config=conf, input_dir=get_testsystems_dir(), output_dir=get_test_output_dir()
)
s1 = SystemStructure(configuration, "structure1")
s2 = SystemStructure(configuration, "structure2")
s1_to_s2 = ProposeMutationRoute(s1, s2)
s1_to_s2.propose_common_core()
s1_to_s2.finish_common_core()
# generate the mutation list for the original
mutation_list = s1_to_s2.generate_mutations_to_common_core_for_mol1()
print(mutation_list.keys())
i = IntermediateStateFactory(
system=s1,
configuration=configuration,
)
perform_mutations(configuration=configuration, i=i, mutation_list=mutation_list)
assert i.current_step == 24
def test_run_28_1h1q_rbfe_production_with_CHARMM():
# Generating output for a run of the CDK2 Ligand System
from transformato import (
IntermediateStateFactory,
ProposeMutationRoute,
SystemStructure,
load_config_yaml,
)
from transformato.mutate import perform_mutations
configuration = load_config_yaml(
config=f"{get_testsystems_dir()}/config/test-28_1h1q_rbfe.yaml",
input_dir=get_testsystems_dir(),
output_dir=get_test_output_dir(),
)
s1 = SystemStructure(configuration, "structure1")
s2 = SystemStructure(configuration, "structure2")
s1_to_s2 = ProposeMutationRoute(s1, s2)
s1_to_s2.propose_common_core()
s1_to_s2.finish_common_core()
mutation_list = s1_to_s2.generate_mutations_to_common_core_for_mol1()
print(mutation_list.keys())
i = IntermediateStateFactory(
system=s1,
configuration=configuration,
)
perform_mutations(
configuration=configuration,
i=i,
mutation_list=mutation_list,
nr_of_mutation_steps_charge=1,
nr_of_mutation_steps_cc=1,
)