Merge branch 'main' into clean-deps

devtools/conda-envs/test_env.yaml

@@ -10,8 +10,8 @@ dependencies:
   - openff-units
   - openmm
   - pymbar
+  - pydantic=1  # TODO: Modify when we support pydantic 2
   - python
-  - pip
 
     # Testing
   - pytest

feflow/protocols/nonequilibrium_cycling.py

@@ -1,6 +1,7 @@
 # Adapted from perses: https://github.com/choderalab/perses/blob/protocol-neqcyc/perses/protocols/nonequilibrium_cycling.py
 
 from typing import Optional, Iterable, List, Dict, Any
+from itertools import chain
 
 import datetime
 import logging
@@ -130,11 +131,16 @@ def _execute(self, ctx, *, state_a, state_b, mapping, settings, **inputs):
 
         phase = self._detect_phase(state_a, state_b)  # infer phase from systems and components
 
-        # Get components from systems if found (None otherwise) -- NOTE: Uses hardcoded keys!
+        # Get receptor components from systems if found (None otherwise) -- NOTE: Uses hardcoded keys!
         receptor_a = state_a.components.get("protein")
         # receptor_b = state_b.components.get("protein")  # Should not be needed
-        ligand_a = mapping.get("ligand").componentA
-        ligand_b = mapping.get("ligand").componentB
+
+        # Get ligand/small-mol components
+        ligand_mapping = mapping["ligand"]
+        ligand_a = ligand_mapping.componentA
+        ligand_b = ligand_mapping.componentB
+
+        # Get solvent components
         solvent_a = state_a.components.get("solvent")
         # solvent_b = state_b.components.get("solvent")  # Should not be needed
 
@@ -163,26 +169,37 @@ def _execute(self, ctx, *, state_a, state_b, mapping, settings, **inputs):
         # Note: by default this is cached to ctx.shared/db.json so shouldn't
         # incur too large a cost
         self.logger.info("Parameterizing molecules")
-        small_mols_a = []
+        # The following creates a dictionary with all the small molecules in the states, with the structure:
+        #    Dict[SmallMoleculeComponent, openff.toolkit.Molecule]
+        # Alchemical small mols
+        alchemical_small_mols_a = {ligand_a: ligand_a.to_openff()}
+        alchemical_small_mols_b = {ligand_b: ligand_b.to_openff()}
+        all_alchemical_mols = alchemical_small_mols_a | alchemical_small_mols_b
+        # non-alchemical common small mols
+        common_small_mols = {}
         for comp in state_a.components.values():
-            if isinstance(comp, SmallMoleculeComponent):
-                small_mols_a.append(comp)
-
-        for comp in small_mols_a:
-            offmol = comp.to_openff()
-            system_generator.create_system(offmol.to_topology().to_openmm(),
-                                           molecules=[offmol])
-            if comp == ligand_a:
-                mol_b = ligand_b.to_openff()
-                system_generator.create_system(mol_b.to_topology().to_openmm(),
-                                               molecules=[mol_b])
+            # TODO: Refactor if/when gufe provides the functionality https://github.com/OpenFreeEnergy/gufe/issues/251
+            if isinstance(comp, SmallMoleculeComponent) and comp not in all_alchemical_mols:
+                common_small_mols[comp] = comp.to_openff()
+
+        # Assign charges to ALL small mols, if unassigned -- more info: Openfe issue #576
+        for off_mol in chain(all_alchemical_mols.values(), common_small_mols.values()):
+            # skip if we already have user charges
+            if not (off_mol.partial_charges is not None and np.any(off_mol.partial_charges)):
+                # due to issues with partial charge generation in ambertools
+                # we default to using the input conformer for charge generation
+                off_mol.assign_partial_charges(
+                    'am1bcc', use_conformers=off_mol.conformers
+                )
+            system_generator.create_system(off_mol.to_topology().to_openmm(),
+                                           molecules=[off_mol])
 
         # c. get OpenMM Modeller + a dictionary of resids for each component
         solvation_settings = settings.solvation_settings
         state_a_modeller, comp_resids = system_creation.get_omm_modeller(
             protein_comp=receptor_a,
             solvent_comp=solvent_a,
-            small_mols=small_mols_a,
+            small_mols=alchemical_small_mols_a | common_small_mols,
             omm_forcefield=system_generator.forcefield,
             solvent_settings=solvation_settings,
         )
@@ -197,7 +214,8 @@ def _execute(self, ctx, *, state_a, state_b, mapping, settings, **inputs):
         # e. create the stateA System
         state_a_system = system_generator.create_system(
             state_a_modeller.topology,
-            molecules=[s.to_openff() for s in small_mols_a],
+            molecules=list(chain(alchemical_small_mols_a.values(),
+                                 common_small_mols.values())),
         )
 
         # 2. Get stateB system
@@ -208,15 +226,10 @@ def _execute(self, ctx, *, state_a, state_b, mapping, settings, **inputs):
             exclude_resids=comp_resids[ligand_a],
         )
 
-        # b. get a list of small molecules for stateB
-        off_mols_state_b = [ligand_b.to_openff(), ]
-        for comp in small_mols_a:
-            if comp != ligand_a:
-                off_mols_state_b.append(comp.to_openff())
-
         state_b_system = system_generator.create_system(
             state_b_topology,
-            molecules=off_mols_state_b,
+            molecules=list(chain(alchemical_small_mols_b.values(),
+                                 common_small_mols.values())),
         )
 
         #  c. Define correspondence mappings between the two systems

feflow/tests/conftest.py

@@ -1,17 +1,16 @@
 # fixtures for chemicalcomponents and chemicalsystems to test protocols with
 import gufe
 import pytest
-import importlib.resources
+from importlib.resources import files, as_file
 from rdkit import Chem
 from gufe.mapping import LigandAtomMapping
 
 
 @pytest.fixture
 def benzene_modifications():
-    with importlib.resources.path('gufe.tests.data',
-                                  'benzene_modifications.sdf') as f:
+    source = files("gufe.tests.data").joinpath("benzene_modifications.sdf")
+    with as_file(source) as f:
         supp = Chem.SDMolSupplier(str(f), removeHs=False)
-
         mols = list(supp)
 
     return {m.GetProp('_Name'): m for m in mols}