add charges to cofactor sdf, fix docs, expose overwrite charges to pl…

…an CLI
OpenFreeEnergy · Jan 24, 2025 · c46e7c1 · c46e7c1
1 parent 37add05
commit c46e7c1
Show file tree

Hide file tree

Showing 11 changed files with 337 additions and 26 deletions.
diff --git a/docs/environment.yaml b/docs/environment.yaml
@@ -21,6 +21,7 @@ dependencies:
 - nbsphinx
 - nbsphinx-link
 - myst-parser
+- threadpoolctl
 - pip:
   - sphinx-design
   - sphinx-toolbox

diff --git a/openfe/tests/data/eg5/eg5_cofactor.sdf b/openfe/tests/data/eg5/eg5_cofactor.sdf
@@ -84,4 +84,15 @@
  26 27  1  0  0  0
 M  CHG  3   3  -1   4  -1   7  -1
 M  END
+
+>  <ofe-name>
+3L9H
+
+>  <atom.dprop.PartialCharge>
+1.3988487435897436 -0.91321825641025633 -0.91321825641025633 -0.91321825641025633 1.5677487435897437 -0.67705125641025643 -0.67705125641025643 -0.77085125641025642 -0.59125125641025633
+0.1833487435897436 0.088048743589743572 -0.42865125641025642 0.064048743589743579 -0.59785125641025638 0.080048743589743579 -0.6198512564102564 0.27474874358974355 -0.28105125641025647
+0.35164874358974357 -0.76515125641025639 -0.11125125641025642 0.54814874358974364 -0.89255125641025634 -0.77805125641025641 0.56384874358974357 -0.71505125641025635 0.38374874358974354
+0.06664874358974357 0.06664874358974357 0.034648743589743576 0.16864874358974358 0.38094874358974357 0.11064874358974358 0.40294874358974359 0.042648743589743576 0.15174874358974358
+0.35724874358974357 0.35724874358974357 0.0010487435897435762
+
 $$$$
diff --git a/openfe/tests/data/openmm_rfe/dummy_charge_ligand_23.sdf b/openfe/tests/data/openmm_rfe/dummy_charge_ligand_23.sdf
@@ -0,0 +1,86 @@
+ligand_23
+     RDKit          3D
+
+ 36 38  0  0  0  0  0  0  0  0999 V2000
+   -1.9600   21.5500  -27.3300 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -1.2900   22.4100  -28.2000 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -1.9600   22.9500  -29.2900 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -3.3000   22.6200  -29.5400 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -3.9700   21.7600  -28.6500 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -3.2900   21.2300  -27.5600 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -5.6400   21.3500  -28.9200 Cl  0  0  0  0  0  0  0  0  0  0  0  0
+   -4.0400   23.1500  -30.7100 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -4.2300   22.4200  -31.6700 O   0  0  0  0  0  0  0  0  0  0  0  0
+   -4.5100   24.4100  -30.6500 N   0  0  0  0  0  0  0  0  0  0  0  0
+   -5.2900   25.1100  -31.5800 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -5.9600   24.5500  -32.6800 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -6.7800   25.3600  -33.4600 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -6.9200   26.6500  -33.1800 N   0  0  0  0  0  0  0  0  0  0  0  0
+   -6.3000   27.2300  -32.1600 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -5.5100   26.4600  -31.3100 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -6.5400   28.5800  -31.8800 N   0  0  0  0  0  0  0  0  0  0  0  0
+   -5.7100   29.4500  -31.2300 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -4.6200   29.1200  -30.8100 O   0  0  0  0  0  0  0  0  0  0  0  0
+   -6.2300   30.8500  -31.0300 C   0  0  1  0  0  0  0  0  0  0  0  0
+   -5.5800   31.7500  -29.9800 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -5.3600   32.0200  -31.4700 C   0  0  1  0  0  0  0  0  0  0  0  0
+   -4.1100   31.7200  -32.0100 F   0  0  0  0  0  0  0  0  0  0  0  0
+   -1.1100   24.0500  -30.3300 Cl  0  0  0  0  0  0  0  0  0  0  0  0
+   -7.3100   30.9400  -31.1600 H   0  0  0  0  0  0  0  0  0  0  0  0
+   -5.8600   32.9000  -31.8800 H   0  0  0  0  0  0  0  0  0  0  0  0
+   -1.4400   21.1300  -26.4800 H   0  0  0  0  0  0  0  0  0  0  0  0
+   -0.2600   22.6600  -28.0200 H   0  0  0  0  0  0  0  0  0  0  0  0
+   -3.8100   20.5600  -26.8900 H   0  0  0  0  0  0  0  0  0  0  0  0
+   -4.3200   24.9800  -29.8400 H   0  0  0  0  0  0  0  0  0  0  0  0
+   -5.8400   23.5000  -32.9100 H   0  0  0  0  0  0  0  0  0  0  0  0
+   -7.3100   24.9400  -34.3000 H   0  0  0  0  0  0  0  0  0  0  0  0
+   -5.0600   26.9100  -30.4300 H   0  0  0  0  0  0  0  0  0  0  0  0
+   -7.4000   29.0100  -32.1800 H   0  0  0  0  0  0  0  0  0  0  0  0
+   -6.3500   32.2000  -29.3600 H   0  0  0  0  0  0  0  0  0  0  0  0
+   -4.9200   31.1500  -29.3500 H   0  0  0  0  0  0  0  0  0  0  0  0
+ 13 32  1  0
+ 13 14  1  0
+ 12 13  2  0
+ 14 15  2  0
+ 12 31  1  0
+ 11 12  1  0
+ 17 34  1  0
+ 15 17  1  0
+ 15 16  1  0
+ 22 23  1  0
+ 17 18  1  0
+ 22 26  1  6
+  8  9  2  0
+ 11 16  2  0
+ 10 11  1  0
+ 20 22  1  0
+ 21 22  1  0
+ 16 33  1  0
+ 18 20  1  0
+ 18 19  2  0
+ 20 25  1  6
+ 20 21  1  0
+  8 10  1  0
+  4  8  1  0
+ 10 30  1  0
+  3 24  1  0
+ 21 35  1  0
+ 21 36  1  0
+  3  4  2  0
+  4  5  1  0
+  2  3  1  0
+  5  7  1  0
+  5  6  2  0
+  2 28  1  0
+  1  2  2  0
+  1  6  1  0
+  6 29  1  0
+  1 27  1  0
+M  END
+>  <atom.dprop.PartialCharge>  (1) 
+-0.097000000000000003 -0.1295 0.050899999999999994 -0.1426 0.050899999999999994 -0.1295 -0.058400000000000007 0.68969999999999998 -0.53810000000000002 -0.46510000000000001 0.1236
+-0.32829999999999998 0.44219999999999998 -0.72699999999999998 0.54220000000000002 -0.27029999999999998 -0.5464 0.69610000000000005 -0.56910000000000005 -0.23069999999999999
+-0.13339999999999999 0.12759999999999999 -0.20530000000000001 -0.058400000000000007 0.1237 0.1027 0.14799999999999999 0.1565 0.1565 0.32550000000000001 0.14199999999999999
+0.022099999999999995 0.20300000000000001 0.33750000000000002 0.094200000000000006 0.094200000000000006
+
+$$$$
diff --git a/openfe/tests/data/openmm_rfe/dummy_charge_ligand_55.sdf b/openfe/tests/data/openmm_rfe/dummy_charge_ligand_55.sdf
@@ -0,0 +1,79 @@
+ligand_55
+     RDKit          3D
+
+ 33 34  0  0  0  0  0  0  0  0999 V2000
+   -1.9600   21.5500  -27.3300 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -1.2900   22.4100  -28.2000 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -1.9600   22.9500  -29.2900 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -3.3000   22.6200  -29.5400 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -3.9700   21.7600  -28.6500 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -3.2900   21.2300  -27.5600 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -5.6400   21.3500  -28.9200 Cl  0  0  0  0  0  0  0  0  0  0  0  0
+   -4.0400   23.1500  -30.7100 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -4.2300   22.4200  -31.6700 O   0  0  0  0  0  0  0  0  0  0  0  0
+   -4.5100   24.4100  -30.6500 N   0  0  0  0  0  0  0  0  0  0  0  0
+   -5.2900   25.1100  -31.5800 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -5.9600   24.5500  -32.6800 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -6.7800   25.3600  -33.4600 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -6.9200   26.6500  -33.1800 N   0  0  0  0  0  0  0  0  0  0  0  0
+   -6.3000   27.2300  -32.1600 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -5.5100   26.4600  -31.3100 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -6.5400   28.5800  -31.8800 N   0  0  0  0  0  0  0  0  0  0  0  0
+   -5.7100   29.4500  -31.2300 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -4.6200   29.1200  -30.8100 O   0  0  0  0  0  0  0  0  0  0  0  0
+   -1.1100   24.0500  -30.3300 Cl  0  0  0  0  0  0  0  0  0  0  0  0
+   -1.4400   21.1300  -26.4800 H   0  0  0  0  0  0  0  0  0  0  0  0
+   -0.2600   22.6600  -28.0200 H   0  0  0  0  0  0  0  0  0  0  0  0
+   -3.8100   20.5600  -26.8900 H   0  0  0  0  0  0  0  0  0  0  0  0
+   -4.3200   24.9800  -29.8400 H   0  0  0  0  0  0  0  0  0  0  0  0
+   -5.8400   23.5000  -32.9100 H   0  0  0  0  0  0  0  0  0  0  0  0
+   -7.3100   24.9400  -34.3000 H   0  0  0  0  0  0  0  0  0  0  0  0
+   -5.0600   26.9100  -30.4300 H   0  0  0  0  0  0  0  0  0  0  0  0
+   -7.4000   29.0100  -32.1800 H   0  0  0  0  0  0  0  0  0  0  0  0
+   -5.1900   31.8500  -30.6800 C   0  0  0  0  0  0  0  0  0  0  0  0
+   -5.5900   32.8600  -30.8200 H   0  0  0  0  0  0  0  0  0  0  0  0
+   -4.9100   31.7200  -29.6300 H   0  0  0  0  0  0  0  0  0  0  0  0
+   -6.2500   30.8500  -31.0300 O   0  0  0  0  0  0  0  0  0  0  0  0
+   -4.3200   31.7100  -31.3200 H   0  0  0  0  0  0  0  0  0  0  0  0
+ 13 26  1  0
+ 13 14  1  0
+ 12 13  2  0
+ 14 15  2  0
+ 12 25  1  0
+ 11 12  1  0
+ 17 28  1  0
+ 15 17  1  0
+ 15 16  1  0
+ 17 18  1  0
+  8  9  2  0
+ 11 16  2  0
+ 10 11  1  0
+ 29 33  1  0
+ 16 27  1  0
+ 18 32  1  0
+ 18 19  2  0
+ 29 32  1  0
+ 29 30  1  0
+  8 10  1  0
+  4  8  1  0
+ 29 31  1  0
+ 10 24  1  0
+  3 20  1  0
+  3  4  2  0
+  4  5  1  0
+  2  3  1  0
+  5  7  1  0
+  5  6  2  0
+  2 22  1  0
+  1  2  2  0
+  1  6  1  0
+  6 23  1  0
+  1 21  1  0
+M  END
+>  <atom.dprop.PartialCharge>  (1) 
+-0.094999969696969694 -0.1279999696969697 0.052400030303030309 -0.1445999696969697 0.052400030303030309 -0.1279999696969697 -0.059899969696969695 0.69270003030303029 -0.54809996969696972
+-0.4610999696969697 0.1306000303030303 -0.2992999696969697 0.44520003030303029 -0.72799996969696967 0.55120003030303033 -0.32229996969696967 -0.51939996969696967 0.74610003030303029
+-0.57699996969696965 -0.059899969696969695 0.1480000303030303 0.15800003030303031 0.15800003030303031 0.33150003030303032 0.1840000303030303 0.028100030303030307 0.1790000303030303
+0.35250003030303029 0.1387000303030303 0.055033030303030306 0.055033030303030306 -0.44289996969696971 0.055033030303030306
+
+$$$$
diff --git a/openfecli/commands/generate_partial_charges.py b/openfecli/commands/generate_partial_charges.py
@@ -1,6 +1,6 @@
 import click
 from openfecli import OFECommandPlugin
-from openfecli.parameters import MOL_DIR, YAML_OPTIONS, OUTPUT_FILE_AND_EXT, NCORES
+from openfecli.parameters import MOL_DIR, YAML_OPTIONS, OUTPUT_FILE_AND_EXT, NCORES, OVERWRITE
 
 
 @click.command(
@@ -21,11 +21,10 @@
     help=NCORES.kwargs["help"],
     default=1,
 )
-@click.option(
-    "--overwrite-charges",
-    is_flag=True,
-    default=False,
-    help="If the charges already present in the molecules should be overwritten."
+@OVERWRITE.parameter(
+    help=OVERWRITE.kwargs["help"],
+    default=OVERWRITE.kwargs["default"],
+    is_flag=True
 )
 def charge_molecules(
         molecules,

diff --git a/openfecli/commands/plan_rbfe_network.py b/openfecli/commands/plan_rbfe_network.py
@@ -5,7 +5,7 @@
 from openfecli.utils import write, print_duration
 from openfecli import OFECommandPlugin
 from openfecli.parameters import (
-    MOL_DIR, PROTEIN, OUTPUT_DIR, COFACTORS, YAML_OPTIONS, NCORES
+    MOL_DIR, PROTEIN, OUTPUT_DIR, COFACTORS, YAML_OPTIONS, NCORES, OVERWRITE
 )
 
 def plan_rbfe_network_main(
@@ -18,6 +18,7 @@ def plan_rbfe_network_main(
     cofactors,
     partial_charge_settings,
     processors,
+    overwrite_charges
 ):
     """Utility method to plan a relative binding free energy network.
 
@@ -36,12 +37,14 @@ def plan_rbfe_network_main(
     protein : ProteinComponent
         protein component for complex simulations, to which the ligands are bound
     cofactors : Iterable[SmallMoleculeComponent]
-        any cofactors alongisde the protein, can be empty list
+        any cofactors alongside the protein, can be empty list
     partial_charge_settings : OpenFFPartialChargeSettings
         how to assign partial charges to the input ligands
         (if they don't already have partial charges).
     processors: int
         The number of processors that should be used when generating the charges
+    overwrite_charges: bool
+        If any partial charges already present on the small molecules should be overwritten
 
     Returns
     -------
@@ -59,7 +62,7 @@ def plan_rbfe_network_main(
 
     charged_small_molecules = bulk_assign_partial_charges(
         molecules=small_molecules,
-        overwrite=False,
+        overwrite=overwrite_charges,
         method=partial_charge_settings.partial_charge_method,
         toolkit_backend=partial_charge_settings.off_toolkit_backend,
         generate_n_conformers=partial_charge_settings.number_of_conformers,
@@ -72,7 +75,7 @@ def plan_rbfe_network_main(
 
         cofactors = bulk_assign_partial_charges(
             molecules=cofactors,
-            overwrite=False,
+            overwrite=overwrite_charges,
             method=partial_charge_settings.partial_charge_method,
             toolkit_backend=partial_charge_settings.off_toolkit_backend,
             generate_n_conformers=partial_charge_settings.number_of_conformers,
@@ -120,12 +123,18 @@ def plan_rbfe_network_main(
     help=NCORES.kwargs["help"],
     default=1,
 )
+@OVERWRITE.parameter(
+    help=OVERWRITE.kwargs["help"],
+    default=OVERWRITE.kwargs["default"],
+    is_flag=True
+)
 @print_duration
 def plan_rbfe_network(
         molecules: list[str], protein: str, cofactors: tuple[str],
         yaml_settings: str,
         output_dir: str,
-        n_cores: int
+        n_cores: int,
+        overwrite_charges: bool
 ):
     """
     Plan a relative binding free energy network, saved as JSON files for
@@ -211,7 +220,8 @@ def plan_rbfe_network(
         protein=protein,
         cofactors=cofactors,
         partial_charge_settings=partial_charge,
-        processors=n_cores
+        processors=n_cores,
+        overwrite_charges=overwrite_charges
     )
     write("\tDone")
     write("")

diff --git a/openfecli/commands/plan_rhfe_network.py b/openfecli/commands/plan_rhfe_network.py
@@ -8,12 +8,12 @@
 from openfecli.utils import write, print_duration
 from openfecli import OFECommandPlugin
 from openfecli.parameters import (
-    MOL_DIR, MAPPER, OUTPUT_DIR, YAML_OPTIONS, NCORES
+    MOL_DIR, MAPPER, OUTPUT_DIR, YAML_OPTIONS, NCORES, OVERWRITE
 )
 
 def plan_rhfe_network_main(
     mapper, mapping_scorer, ligand_network_planner, small_molecules,
-    solvent, partial_charge_settings, processors
+    solvent, partial_charge_settings, processors, overwrite_charges
 ):
     """Utility method to plan a relative hydration free energy network.
 
@@ -34,6 +34,8 @@ def plan_rhfe_network_main(
         (if they don't already have partial charges).
     processors: int
         The number of processors that should be used when generating the charges
+    overwrite_charges: bool
+        If any partial charges already present on the small molecules should be overwritten
 
     Returns
     -------
@@ -50,7 +52,7 @@ def plan_rhfe_network_main(
 
     charged_small_molecules = bulk_assign_partial_charges(
         molecules=small_molecules,
-        overwrite=False,
+        overwrite=overwrite_charges,
         method=partial_charge_settings.partial_charge_method,
         toolkit_backend=partial_charge_settings.off_toolkit_backend,
         generate_n_conformers=partial_charge_settings.number_of_conformers,
@@ -92,8 +94,13 @@ def plan_rhfe_network_main(
     help=NCORES.kwargs["help"],
     default=1,
 )
+@OVERWRITE.parameter(
+    help=OVERWRITE.kwargs["help"],
+    default=OVERWRITE.kwargs["default"],
+    is_flag=True
+)
 @print_duration
-def plan_rhfe_network(molecules: List[str], yaml_settings: str, output_dir: str, n_cores: int):
+def plan_rhfe_network(molecules: List[str], yaml_settings: str, output_dir: str, n_cores: int, overwrite_charges: bool):
     """
     Plan a relative hydration free energy network, saved as JSON files for
     the quickrun command.
@@ -169,7 +176,8 @@ def plan_rhfe_network(molecules: List[str], yaml_settings: str, output_dir: str,
         small_molecules=small_molecules,
         solvent=solvent,
         partial_charge_settings=partial_charge,
-        processors=n_cores
+        processors=n_cores,
+        overwrite_charges=overwrite_charges
     )
     write("\tDone")
     write("")

diff --git a/openfecli/parameters/__init__.py b/openfecli/parameters/__init__.py
@@ -8,4 +8,4 @@
 from .protein import PROTEIN
 from .molecules import MOL_DIR, COFACTORS
 from .plan_network_options import YAML_OPTIONS
-from .misc import NCORES
+from .misc import NCORES, OVERWRITE
diff --git a/openfecli/parameters/misc.py b/openfecli/parameters/misc.py
@@ -4,4 +4,11 @@
     "-n",
     "--n-cores",
     help="The number of cores which should be used for multiprocessing stages."
+)
+
+OVERWRITE = Option(
+    "--overwrite-charges",
+    is_flag=True,
+    default=False,
+    help="If the charges already present in the molecules should be overwritten."
 )