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Explicitly Defining Ligand Networks

OpenFE provides utilities for ingesting networks from ordinary Python datastructures like list[tuple[str, str]] and list[tuple[int, int]].

Each string or integer respectively names or indexes a ligand, and tuples represent edges in the network.

This explicit definition of networks supports use-cases where the desired edges are known and may be helpful for loading networks from other tools.

Although this is the most flexible way to define a LigandNetwork, we encourage you to use openfe helper functionality when possible for performance, reproducibility, and ease of use:

• Loading Ligand Networks Exported by Orion or FEP+

• Planning a Ligand Network

Load the ligands

This cookbook assumes you’ve already loaded a collection of SmallMoleculeComponent objects into an iterable called ligands.

For more information, see Loading Small Molecules.

%matplotlib inline
from rdkit import Chem
import openfe

supplier = Chem.SDMolSupplier("assets/somebenzenes.sdf", removeHs=False)
ligands = [openfe.SmallMoleculeComponent(mol) for mol in supplier]

ligands

[SmallMoleculeComponent(name=benzene),
 SmallMoleculeComponent(name=toluene),
 SmallMoleculeComponent(name=phenol),
 SmallMoleculeComponent(name=benzonitrile),
 SmallMoleculeComponent(name=anisole),
 SmallMoleculeComponent(name=benzaldehyde),
 SmallMoleculeComponent(name=styrene)]

Select an atom mapper

As we will only specify the topology of the network, OpenFE must generate atom mappings for us. For this, it needs an atom mapper; for more information, see Choose an Atom Mapper:

mapper = openfe.setup.LomapAtomMapper(
    threed=True, # Use atom positions to prune symmetric mappings
    max3d=1.0, # Forbid mapping between atoms more than 1.0 Å apart
    element_change=False, # Forbid mappings that change an atoms element
)

Define the network

We can inspect the ligands to identify what we’re working with:

print(*enumerate(ligands), sep="\n")

(0, SmallMoleculeComponent(name=benzene))
(1, SmallMoleculeComponent(name=toluene))
(2, SmallMoleculeComponent(name=phenol))
(3, SmallMoleculeComponent(name=benzonitrile))
(4, SmallMoleculeComponent(name=anisole))
(5, SmallMoleculeComponent(name=benzaldehyde))
(6, SmallMoleculeComponent(name=styrene))

Then, define the network topology by specifying transformations between ligands, either by name or index:

topology_by_names = [
    ("styrene", "toluene"),
    ("benzonitrile", "toluene"),
    ("toluene", "benzene"),
    ("benzene", "phenol"),
    ("phenol", "anisole"),
    ("phenol", "benzaldehyde"),
]

topology_by_indices = [
    (6, 1),
    (3, 1),
    (1, 0),
    (0, 2),
    (2, 4),
    (2, 5),
]

Create the network

from openfe.setup import ligand_network_planning

Now create the LigandNetwork object from the specified edges:

ligand_network_from_names = ligand_network_planning.generate_network_from_names(
    ligands=ligands,
    mapper=mapper,
    names=topology_by_names,
)

ligand_network_from_indices = ligand_network_planning.generate_network_from_indices(
    ligands=ligands,
    mapper=mapper,
    indices=topology_by_indices,
)

parallel map scoring

/Users/atravitz/micromamba/envs/openfe-notebooks/lib/python3.13/site-packages/gufe/components/explicitmoleculecomponent.py:74: UserWarning: RDKit does not preserve Mol properties when pickled by default, which may drop e.g. atom charges; consider setting `Chem.SetDefaultPickleProperties(Chem.PropertyPickleOptions.AllProps)`
  warnings.warn(

parallel map scoring

/Users/atravitz/micromamba/envs/openfe-notebooks/lib/python3.13/site-packages/gufe/components/explicitmoleculecomponent.py:74: UserWarning: RDKit does not preserve Mol properties when pickled by default, which may drop e.g. atom charges; consider setting `Chem.SetDefaultPickleProperties(Chem.PropertyPickleOptions.AllProps)`
  warnings.warn(
/Users/atravitz/micromamba/envs/openfe-notebooks/lib/python3.13/site-packages/gufe/components/explicitmoleculecomponent.py:74: UserWarning: RDKit does not preserve Mol properties when pickled by default, which may drop e.g. atom charges; consider setting `Chem.SetDefaultPickleProperties(Chem.PropertyPickleOptions.AllProps)`
  warnings.warn(

Visualise the network

For more ways to visualize a LigandNetwork, see Visualizing Ligand Networks.

from openfe.utils.atommapping_network_plotting import plot_atommapping_network

plot_atommapping_network(ligand_network_from_names)