Add protein-ligand complex testing (#61)

* reuse hybrid topology atom list. Optimization * Short protein-ligand complex test implemented. Marked as slow.
OpenFreeEnergy · Aug 19, 2024 · b3f230a · b3f230a
1 parent eddaf1d
commit b3f230a
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diff --git a/feflow/tests/conftest.py b/feflow/tests/conftest.py
@@ -50,7 +50,7 @@ def benzene_modifications(gufe_data_dir):
 # Components fixtures
 
 
-@pytest.fixture
+@pytest.fixture(scope="session")
 def solvent_comp():
  yield gufe.SolventComponent(positive_ion="Na", negative_ion="Cl")
 
@@ -65,6 +65,24 @@ def toluene(benzene_modifications):
  return gufe.SmallMoleculeComponent(benzene_modifications["toluene"])
 
 
+@pytest.fixture(scope="session")
+def tyk2_protein():
+ filepath = files("feflow.tests.data").joinpath("tyk2_protein.pdb")
+ return gufe.ProteinComponent.from_pdb_file(str(filepath))
+
+
+@pytest.fixture(scope="session")
+def tyk2_ligand_ejm_54():
+ filepath = files("feflow.tests.data").joinpath("tyk2_lig_ejm_54.sdf")
+ return gufe.SmallMoleculeComponent.from_sdf_file(str(filepath))
+
+
+@pytest.fixture(scope="session")
+def tyk2_ligand_ejm_46():
+ filepath = files("feflow.tests.data").joinpath("tyk2_lig_ejm_46.sdf")
+ return gufe.SmallMoleculeComponent.from_sdf_file(str(filepath))
+
+
 # Systems fixtures
 
 
@@ -88,6 +106,20 @@ def toluene_solvent_system(toluene, solvent_comp):
  return gufe.ChemicalSystem({"ligand": toluene, "solvent": solvent_comp})
 
 
+@pytest.fixture
+def tyk2_lig_ejm_46_complex(tyk2_protein, tyk2_ligand_ejm_46, solvent_comp):
+ return gufe.ChemicalSystem(
+ {"protein": tyk2_protein, "ligand": tyk2_ligand_ejm_46, "solvent": solvent_comp}
+ )
+
+
+@pytest.fixture
+def tyk2_lig_ejm_54_complex(tyk2_protein, tyk2_ligand_ejm_54, solvent_comp):
+ return gufe.ChemicalSystem(
+ {"protein": tyk2_protein, "ligand": tyk2_ligand_ejm_54, "solvent": solvent_comp}
+ )
+
+
 # Settings fixtures
 
 
@@ -103,6 +135,7 @@ def short_settings():
  settings.integrator_settings.nonequilibrium_steps = 250
  settings.work_save_frequency = 50
  settings.traj_save_frequency = 250
+ settings.num_cycles = 1
 
  return settings
 
@@ -218,3 +251,20 @@ def broken_mapping(benzene, toluene):
  componentA_to_componentB=broken_mapping,
  )
  return broken_mapping_obj
+
+
+@pytest.fixture
+def mapping_tyk2_54_to_46(tyk2_ligand_ejm_54, tyk2_ligand_ejm_46):
+ """
+ Mapping object from ligand ejm_54 to ejm_46 for the Tyk2 dataset.
+
+ It generates the mapping on runtime using the Kartograf mapper.
+ """
+ from kartograf import KartografAtomMapper
+
+ atom_mapper = KartografAtomMapper()
+ mapping_obj = next(
+ atom_mapper.suggest_mappings(tyk2_ligand_ejm_54, tyk2_ligand_ejm_46)
+ )
+
+ return mapping_obj
diff --git a/feflow/tests/data/tyk2_lig_ejm_46.sdf b/feflow/tests/data/tyk2_lig_ejm_46.sdf
@@ -0,0 +1,206 @@
+lig_ejm_46
+ 3D
+ Schrodinger Suite 2022-3.
+ 36 38 0 0 1 0 999 V2000
+ -4.7641 -2.8360 -16.5091 H 0 0 0 0 0 0
+ -5.3551 -3.6988 -16.2343 C 0 0 0 0 0 0
+ -4.7691 -4.9763 -16.2133 C 0 0 0 0 0 0
+ -5.5322 -6.1012 -15.8489 C 0 0 0 0 0 0
+ -6.8971 -5.9556 -15.4808 C 0 0 0 0 0 0
+ -7.4860 -4.6658 -15.5235 C 0 0 0 0 0 0
+ -6.7149 -3.5494 -15.9013 C 0 0 0 0 0 0
+ -7.1642 -2.5677 -15.9366 H 0 0 0 0 0 0
+ -9.1609 -4.4168 -15.1573 Cl 0 0 0 0 0 0
+ -7.7099 -7.1391 -15.0412 C 0 0 0 0 0 0
+ -8.1270 -7.2082 -13.8848 O 0 0 0 0 0 0
+ -7.9085 -8.0557 -16.0048 N 0 0 0 0 0 0
+ -7.4364 -7.8700 -16.8774 H 0 0 0 0 0 0
+ -8.7302 -9.2129 -16.0071 C 0 0 0 0 0 0
+ -9.5845 -9.6010 -14.9550 C 0 0 0 0 0 0
+ -10.3859 -10.7400 -15.1393 C 0 0 0 0 0 0
+ -10.3615 -11.5002 -16.2562 N 0 0 0 0 0 0
+ -9.5413 -11.1483 -17.2750 C 0 0 0 0 0 0
+ -8.7209 -9.9970 -17.1753 C 0 0 0 0 0 0
+ -8.0953 -9.6795 -17.9932 H 0 0 0 0 0 0
+ -9.5567 -11.9338 -18.4642 N 0 0 0 0 0 0
+ -10.3627 -12.5404 -18.5590 H 0 0 0 0 0 0
+ -8.6358 -12.0325 -19.4477 C 0 0 0 0 0 0
+ -7.5743 -11.4049 -19.4949 O 0 0 0 0 0 0
+ -9.0140 -13.0112 -20.5101 C 0 0 0 0 0 0
+ -8.6036 -12.7155 -21.9369 C 0 0 0 0 0 0
+ -7.9023 -13.8059 -21.1663 C 0 0 0 0 0 0
+ -8.1243 -14.8374 -21.4290 H 0 0 0 0 0 0
+ -6.8721 -13.6163 -20.8685 H 0 0 0 0 0 0
+ -8.0346 -11.8121 -22.1455 H 0 0 0 0 0 0
+ -9.3177 -12.9952 -22.7091 H 0 0 0 0 0 0
+ -9.9630 -13.5266 -20.3808 H 0 0 0 0 0 0
+ -11.0715 -11.0494 -14.3644 H 0 0 0 0 0 0
+ -9.6709 -9.0420 -14.0358 H 0 0 0 0 0 0
+ -4.7565 -7.6418 -15.8644 Cl 0 0 0 0 0 0
+ -3.7260 -5.0905 -16.4764 H 0 0 0 0 0 0
+ 1 2 1 0 0 0
+ 2 7 1 0 0 0
+ 2 3 2 0 0 0
+ 3 4 1 0 0 0
+ 3 36 1 0 0 0
+ 4 5 2 0 0 0
+ 4 35 1 0 0 0
+ 5 6 1 0 0 0
+ 5 10 1 0 0 0
+ 6 7 2 0 0 0
+ 6 9 1 0 0 0
+ 7 8 1 0 0 0
+ 10 11 2 0 0 0
+ 10 12 1 0 0 0
+ 12 13 1 0 0 0
+ 12 14 1 0 0 0
+ 14 19 1 0 0 0
+ 14 15 2 0 0 0
+ 15 16 1 0 0 0
+ 15 34 1 0 0 0
+ 16 17 2 0 0 0
+ 16 33 1 0 0 0
+ 17 18 1 0 0 0
+ 18 19 2 0 0 0
+ 18 21 1 0 0 0
+ 19 20 1 0 0 0
+ 21 22 1 0 0 0
+ 21 23 1 0 0 0
+ 23 24 2 0 0 0
+ 23 25 1 0 0 0
+ 25 27 1 0 0 0
+ 25 26 1 0 0 0
+ 25 32 1 0 0 0
+ 26 27 1 0 0 0
+ 26 30 1 0 0 0
+ 26 31 1 0 0 0
+ 27 28 1 0 0 0
+ 27 29 1 0 0 0
+M END
+> <s_m_source_file>
+ligprep_tyk2.smi
+
+> <i_m_source_file_index>
+6
+
+> <i_lp_mmshare_version>
+53161
+
+> <i_f3d_flags>
+0
+
+> <s_epik_input>
+Q2xjMVtjSF1bY0hdW2NIXWMoQ2wpYzFDKD1PKVtOSF1jMltjSF1bY0hdbmMoW2NIXTIpW05IXUMoPU8pW0NIXTNbQ0gyXVtDSDJdMw==
+
+> <s_epik_cmdline>
+J2VwaWtfcHl0aG9uJywgJy1waHQnLCAnMC4wJywgJy1waCcsICc3LjQnLCAnLXRuJywgJzgnLCAnLW1hJywgJzUwMCcsICctaW1hZScsICc8aW5maWxlLm1hZT4nLCAnLW9tYWUnLCAnPG91dGZpbGUubWFlPic=
+
+> <r_lp_tautomer_probability>
+1
+
+> <r_epik_Ionization_Penalty>
+ 0.0034
+
+> <r_epik_Ionization_Penalty_Charging>
+ 0.0000
+
+> <r_epik_Ionization_Penalty_Neutral>
+ 0.0034
+
+> <r_epik_State_Penalty>
+ -0.0000
+
+> <r_epik_Charging_Adjusted_Penalty>
+0
+
+> <i_epik_Tot_Q>
+0
+
+> <i_epik_Tot_abs_Q>
+0
+
+> <s_lp_Force_Field>
+S-OPLS
+
+> <r_lp_Energy>
+49.5212
+
+> <b_lp_Chiralities_Consistent>
+1
+
+> <s_lp_Variant>
+lig_ejm_46-1
+
+> <s_i_glide_gridfile>
+glide-grid_TYK2-4GIH
+
+> <i_i_glide_lignum>
+6
+
+> <i_i_glide_rotatable_bonds>
+6
+
+> <r_i_docking_score>
+-9.61568735798166
+
+> <r_i_glide_ligand_efficiency>
+-0.418073363390507
+
+> <r_i_glide_ligand_efficiency_sa>
+-1.1889450320591
+
+> <r_i_glide_ligand_efficiency_ln>
+-2.32516039339236
+
+> <r_i_glide_gscore>
+-9.61568735798166
+
+> <r_i_glide_lipo>
+-3.62915830081149
+
+> <r_i_glide_hbond>
+-0.57340247290156
+
+> <r_i_glide_metal>
+-0
+
+> <r_i_glide_rewards>
+-2.28077531878579
+
+> <r_i_glide_evdw>
+-50.9746627807617
+
+> <r_i_glide_ecoul>
+-8.24195003509521
+
+> <r_i_glide_erotb>
+0.65267437881954
+
+> <r_i_glide_esite>
+0
+
+> <r_i_glide_emodel>
+-102.027343960114
+
+> <r_i_glide_energy>
+-59.2166128158569
+
+> <r_i_glide_einternal>
+6.72696387482574e-07
+
+> <i_i_glide_confnum>
+1
+
+> <i_i_glide_posenum>
+2
+
+> <r_i_glide_eff_state_penalty>
+-0
+
+> <r_i_glide_rmsd>
+0.0499811632888399
+
+> <s_glide_core_constrain_type>
+snapped_core_restrain
+
+$$$$