An improved script to extract a ligand from a protein-ligand complex and assign bond orders

split_complex_v2.py

#!/usr/bin/env python

import sys
from prody import *
from rdkit import Chem
from rdkit.Chem import AllChem
from io import StringIO
import pypdb


def get_pdb_components(pdb_id):
    """
    Split a protein-ligand pdb into protein and ligand components
    :param pdb_id:
    :return:
    """
    pdb = parsePDB(pdb_id)
    protein = pdb.select('protein')
    ligand = pdb.select('not protein and not water')
    return protein, ligand


def process_ligand(ligand, res_name):
    """
    Add bond orders to a pdb ligand
    1. Select the ligand component with name "res_name"
    2. Get the corresponding SMILES from pypdb
    3. Create a template molecule from the SMILES in step 2
    4. Write the PDB file to a stream
    5. Read the stream into an RDKit molecule
    6. Assign the bond orders from the template from step 3
    :param ligand: ligand as generated by prody
    :param res_name: residue name of ligand to extract
    :return: molecule with bond orders assigned
    """
    output = StringIO()
    sub_mol = ligand.select(f"resname {res_name}")
    chem_desc = pypdb.describe_chemical(f"{res_name}")
    sub_smiles = chem_desc["describeHet"]["ligandInfo"]["ligand"]["smiles"]
    template = AllChem.MolFromSmiles(sub_smiles)
    writePDBStream(output, sub_mol)
    pdb_string = output.getvalue()
    rd_mol = AllChem.MolFromPDBBlock(pdb_string)
    new_mol = AllChem.AssignBondOrdersFromTemplate(template, rd_mol)
    return new_mol


def write_pdb(protein, pdb_name):
    """
    Write a prody protein to a pdb file
    :param protein: protein object from prody
    :param pdb_name: base name for the pdb file
    :return: None
    """
    output_pdb_name = f"{pdb_name}_protein.pdb"
    writePDB(f"{output_pdb_name}", protein)
    print(f"wrote {output_pdb_name}")


def write_sdf(new_mol, pdb_name, res_name):
    """
    Write an RDKit molecule to an SD file
    :param new_mol:
    :param pdb_name:
    :param res_name:
    :return:
    """
    outfile_name = f"{pdb_name}_{res_name}_ligand.sdf"
    writer = Chem.SDWriter(f"{outfile_name}")
    writer.write(new_mol)
    print(f"wrote {outfile_name}")


def main(pdb_name):
    """
    Read Ligand Expo data, split pdb into protein and ligands,
    write protein pdb, write ligand sdf files
    :param pdb_name: id from the pdb, doesn't need to have an extension
    :return:
    """
    protein, ligand = get_pdb_components(pdb_name)
    write_pdb(protein, pdb_name)

    res_name_list = list(set(ligand.getResnames()))
    for res in res_name_list:
        new_mol = process_ligand(ligand, res)
        write_sdf(new_mol, pdb_name, res)


if __name__ == "__main__":
    if len(sys.argv) == 2:
        main(sys.argv[1])
    else:
        print("Usage: {sys.argv[1]} pdb_id", file=sys.stderr)

Hello Mr. Walter.

While I tried to implement this piece of code, I was stopped by the following error
module 'pypdb' has no attribute 'describe_chemical'

I see that it has been 3 years since you have posted this code.
Looks like things have changed. Can you help me?

So it turns out that the describe chemical function has been commented out of the pypdb. maby try uncommenting it?

Dear Dr. Walters,

Thank you for sharing this script; it works like a charm! The only thing I had to update was due to the changes in pypdb. Instead of
sub_smiles = chem_desc["describeHet"]["ligandInfo"]["ligand"]["smiles"]
I used

    sub_smiles = None
    for item in chem_desc.get('pdbx_chem_comp_descriptor', []):
        if item.get('type') == 'SMILES':
            sub_smiles = item.get('descriptor')
            break

Thank you for your great work.

I have a question that in the process_ligand function, why we do not directly use sub_mol instead of new_mol? Is it will change the coordinate of the extracted ligand?

I need to keep the 3D structure of ligand (conformer) when splitting. How can we do that?

The variable sub_mol is a Prody molecule. To assign bond orders, we need to convert this to an RDKit molecule. To this, we first convert the prody_ligand molecule to a PDB string, then parse the PDB string with the RDKit. I've added a commented version of parse_ligand below. Note that new_mol contains the coordinates from the original pdb.

# create a StringIO object that will hold the PDB string
    output = StringIO()
# select the Prody molecule with the ligand
    sub_mol = ligand.select(f"resname {res_name}")
# get the SMILES for the ligand
    chem_desc = pypdb.describe_chemical(f"{res_name}")
    sub_smiles = chem_desc["describeHet"]["ligandInfo"]["ligand"]["smiles"]
# create an RDKit molecule with bond orders from the SMILES
    template = AllChem.MolFromSmiles(sub_smiles)
# write the Prody molecule as a PDB to a string
    writePDBStream(output, sub_mol)
# get the  pdb string from the StringIO object
    pdb_string = output.getvalue()
# create an RDKit molecule from the pdb string
    rd_mol = AllChem.MolFromPDBBlock(pdb_string)
# use the template molecule to assign bond orders
    new_mol = AllChem.AssignBondOrdersFromTemplate(template, rd_mol)
# return the molecule with bond orders
    return new_mol