Ligand Modeler

Create Ligand Modeler project

Let’s walk through how to create a Ligand Reader & Modeler project. You will need at least one ligand SDF file. If you plan to use a PDB Reader project, make sure that the corresponding PDB Reader project contains a ligand. In the example below, we’ll use only an SDF file.

If you are creating the project based on a PDB Reader project, you will need to provide the following options:

  • pdbreader_project_id (str): The project ID of a PDB Reader project that contains at least one ligand.

  • native_ligand (str): The name of the native ligand from the specified PDB Reader project.

  • Optional Advanced Options when using pdbreader_project_id:

    • complete_ring_chain (bool): Match only when the atoms inside each ring are exactly the same — requires an identical ring subgraph (atoms and bonds). default: False

    • strict_match (bool): For pre-aligned molecules, tightly enforce coordinate agreement by snapping positions within a small tolerance for a stricter fit. default: True

    • handle_chirality (bool): Preserve stereochemistry during alignment by considering chirality centers and geometric isomers. default: True

Note: You can check the available native_ligand values by using the get_native_ligands(pdbreader_project_id) method.

lrmbuilder = molcube.create_ligand_modeler_project()

# alt: pdbreader_project_id = pdbreader.projectId
pdbreader_project_id = '78080ec8-bfcd-4141-8f22-f0ae805374ff'

ligands_data = lrmbuilder.get_native_ligands(pdbreader_project_id)
# Native ligand found - Chain: HETE_C, Residue Name: 53U, Residue Index: 2001

lrmbuilder.create_project(
    title="test_LRM",
    ff="amberff",
    sdf_paths=["./1a.sdf", "1b.sdf"],
    pdbreader_project_id=pdbreader_project_id,
    native_ligand={
        "chainIndex": "HETE_C",
        "residueIndex": 2001
    },
)

Modify SDF file (optional)

You can optionally modify the dihedral angle in the ligand SDF file. This step can be skipped.

To do this, first use the check_atom_index() method along with interactive clicking to identify the indices of the atoms involved. The check_atom_index() method requires the name of the SDF file as input, which you can find via lrmbuilder.files_data.

Once the desired atom indices are known, use the change_dihedral() method to obtain a dictionary containing the modified ligand data needed for the next step. You should create a list and append each output from change_dihedral() to this list for use in the following step.

check_atom_index() options:

  • file_name (str): The name of the target SDF file where the dihedral will be changed.

  • visual_protein (bool): Whether to visualize the protein together with the ligand (default: False).

change_dihedral() options:

  • file_name (str): The name of the target SDF file.

  • atom_index_1 (int): The first atom defining the rotation axis. The rotation axis is directed from atom_index_1 to atom_index_2.

  • atom_index_2 (int): The second atom defining the rotation axis. The part of the molecule connected to this atom (excluding the bond to atom_index_1) will be rotated.

  • angle (int): The rotation angle in degrees (between 0 and 360).

  • visual_protein (bool): Whether to visualize the protein together with the ligand (default: False).

Note: The direction from atom_index_1 to atom_index_2 determines which fragment of the molecule will rotate. The atoms connected to atom_index_2, excluding the path back to atom_index_1, will be rotated around the axis defined by the bond.

>>> lrmbuilder.check_atom_index('1a.sdf')
[return value is a nglview; click an atom to show its index]

>>> modified_ligand = lrmbuilder.change_dihedral('1a.sdf', 30, 8, 180)
[another nglview object showing the new conformation]

Finally, use the gen_ligand_ff() method to generate ligand force fields. The following arguments are available for this method:

  • ligand_ff (list[LigandForceField]): A list of ligand force fields to be generated.

  • modified_ligands (list, optional): A list of modified ligand outputs from the change_dihedral() method. Default is an empty list ([]).

from molcube.ligand_modeler.enum import *

ligand_ff = [LigandForceField.OPENFF_FAST]
lrmbuilder.gen_ligand_ff(ligand_ff)