Parameterizing receptor from Python

Parameterizing the receptor means creating a Polymer instance. That can be done from a PDB string, or directly from a PDB file. The following example runs from test/polymer_data using file AHHY.pdb.

from meeko import Polymer

fn = "AHHY.pdb"
polymer = Polymer.from_pdb_file(fn)

# alternatively, use PDB string (not file)
with open(fn) as f:
    pdb_string = f.read()
polymer = Polymer.from_pdb_string(pdb_string)

The parameterization is performed residue by residue, using the same code that parameterizes ligands. To define how to parameterize a receptor, create an instance of MoleculePreparation and pass it to the constructor:

from meeko import MoleculePreparation

mk_prep = MoleculePreparation(
    load_atom_params=["openff-2.3.0"],
    charge_model="nagl",  # requires a recent version of OpenFF-toolkit
    merge_these_atom_types=[],
    rigid_macrocycles=True,
)
polymer = Polymer.from_pdb_string(pdb_string, mk_prep=mk_prep)

See Advanced ligand preparation for how to configure MoleculePreparation. It is valid for both ligands and receptors.

Flexible side chains

Make a side chain flexible. Here, "A:3" is the residue ID, where A is the chain, and 3 is the residue number.

polymer.flexibilize_sidechain("A:3", mk_prep)

And make all rigid again, or one in particular:

polymer.rigidify_all(mk_prep)
polymer.rigidify_sidechain("A:3", mk_prep)

The instance of mk_prep must be passed because flexibilizing and rigidifying side chains involves setting bonds as rotatable or not. If the mk_prep instance is configured differently than the one used to parameterize the polymer, than flexibilized and rigidified residues will have different parameters. It is possible to reparameterize an entire polymer or specific residues:

polymer.parameterize(mk_prep)
polymer.monomers["A:3"].parameterize(mk_prep, "A:3")