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Relative Free Energy Alchemical Network Planners#

To simplify the process of creating an Alchemical Network for Relative Free Energy calculations, openfe offers two convenience Alchemical Network Planner classes; RBFEAlchemicalNetworkPlanner and RHFEAlchemicalNetworkPlanner.

Overview#

To create an AlchemicalNetwork using the Alchemical Planners, the following steps must be followed:

  1. Create appropriate ChemicalComponents

  2. Choosing an appropriate atom mapper, scorer, and network generator

  3. Create an Alchemical Planner

  4. Create the AlchemicalNetwork

Relative Binding Free Energy (RBFE)#

Here we demonstrate how to use the RBFEAlchemicalNetworkPlanner to create an RBFE AlchemicalNetwork

Creating ChemicalComponents#

First we define the ChemicalComponents which we want to represent in our AlchemicalNetwork.

[1]:

from rdkit import Chem
from openfe import SmallMoleculeComponent, SolventComponent, ProteinComponent

[2]:

# Some SmallMoleculeComponents defining the ligands we want to transform between
ligands = [
    SmallMoleculeComponent(m)
    for m in Chem.SDMolSupplier("assets/somebenzenes.sdf", removeHs=False)
]

# The ProteinComponent which will be present in our complex simulations
protein = ProteinComponent.from_pdb_file("assets/t4_lysozyme.pdb")

# The SolventComponent defining our system's solvation
solvent = SolventComponent()

Choosing an atom mapper, scorer and network generator#

Here we choose to use the KartografAtomMapper alongside the Lomap scorer.

For our network we choose to create a minimum spanning network using generate_minimal_spanning_network.

[3]:

from openfe.setup.atom_mapping import KartografAtomMapper
from openfe.setup.atom_mapping.lomap_scorers import default_lomap_score
from openfe.setup.ligand_network_planning import generate_minimal_spanning_network

Building the RBFEAlchemicalNetworkPlanner and getting an AlchemicalNetwork#

Finally we can use the RBFEAlchemicalNetworkPlanner to create an AlchemicalNetwork.

Internally the Network Planner will:

  1. Create a LigandNetwork (accessible under the ._ligand_network attribute).

  2. Create two Transformation per edge of the LigandNetwork, one for each of the complex and solvent legs of the RBFE alchemical cycle.

  3. Add all Transformations to a single AlchemicalNetwork.

[4]:

from openfe.setup.alchemical_network_planner import RBFEAlchemicalNetworkPlanner

# Build the planner
alchem_planner = RBFEAlchemicalNetworkPlanner(
    name="project",
    mappers=[KartografAtomMapper()],
    mapping_scorer=default_lomap_score,
    ligand_network_planner=generate_minimal_spanning_network,
)

# Create the AlchemicalNetwork
alchemical_network = alchem_planner(
    ligands=ligands,
    solvent=solvent,
    protein=protein
)

Relative Hydration Free Energy (RHFE)#

Similarly, an RHFE AlchemicalNetwork can be created using the RHFEAlchemicalNetworkPlanner.

Building the RHFEAlchemicalNetworkPlanner and getting an AlchemicalNetwork#

Here we use the same ChemicalComponents, atom mapper, scorer, and network planner as used in the RBFE section above.

The RHFEAlchemicalNetworkPlanner will:

  1. Create a new LigandNetwork.

  2. Create two Transformation per LigandNetwork edge, one for the solvent and vacuum legs of the transformation, setting appropriate nonbonded methods and cutoffs for the periodic and nonperiodic simulations.

  3. Combine all the Transformations into an AlchemicalNetwork.

[5]:

from openfe.setup.alchemical_network_planner import RHFEAlchemicalNetworkPlanner

# Build the planner
alchem_planner = RHFEAlchemicalNetworkPlanner(
    name="project",
    mappers=[KartografAtomMapper()],
    mapping_scorer=default_lomap_score,
    ligand_network_planner=generate_minimal_spanning_network,
)

# Create the AlchemicalNetwork
alchemical_network = alchem_planner(
    ligands=ligands,
    solvent=solvent,
)