parse_complexes.py

#!/usr/bin/env python

# Split a protein-ligand complex into protein and ligands and assign ligand bond orders using SMILES strings from Ligand Export
# Code requires Python 3.6

import sys
from prody import *
import pandas as pd
from rdkit import Chem
from rdkit.Chem import AllChem
from io import StringIO
import requests

from mpi4py import MPI
from mpi4py.futures import MPICommExecutor
from mpi4py.futures import MPIPoolExecutor

import re
from functools import partial
import gzip
from rdkit.Chem.Descriptors import ExactMolWt
import numpy as np

import os

# minimum molecular weight to consider sth a ligand
mol_wt_cutoff = 100

# all punctuation
punctuation_regex  = r"""(\(|\)|\.|=|#|-|\+|\\|\/|:|~|@|\?|>>?|\*|\$|\%[0-9]{2}|[0-9])"""

# tokenization regex (Schwaller)
molecule_regex = r"""(\[[^\]]+]|Br?|Cl?|N|O|S|P|F|I|b|c|n|o|s|p|\(|\)|\.|=|#|-|\+|\\|\/|:|~|@|\?|>>?|\*|\$|\%[0-9]{2}|[0-9])"""

max_seq = 2046 # = 2048 - 2 (accounting for [CLS] and [SEP])
max_smiles = 510 # = 512 - 2

def get_protein_sequence_and_coords(receptor):
    calpha = receptor.select('calpha')
    xyz = calpha.getCoords()
    seq = calpha.getSequence()
    return seq, xyz.tolist()

def tokenize_ligand(mol):
    # convert to SMILES and map atoms
    smi = Chem.MolToSmiles(mol)

    # position of atoms in SMILES (not counting punctuation)
    atom_order = [int(s) for s in list(filter(None,re.sub(r'[\[\]]','',mol.GetProp("_smilesAtomOutputOrder")).split(',')))]

    # tokenize the SMILES
    tokens = list(filter(None, re.split(molecule_regex, smi)))

    # remove punctuation
    masked_tokens = [re.sub(punctuation_regex,'',s) for s in tokens]

    k = 0
    token_pos = []
    for i,token in enumerate(masked_tokens):
        if token != '':
            token_pos.append(tuple(mol.GetConformer().GetAtomPosition(atom_order[k])))
            k += 1
        else:
            token_pos.append((np.nan, np.nan, np.nan))

    return smi, token_pos

def read_ligand_expo():
    """
    Read Ligand Expo data, try to find a file called
    Components-smiles-stereo-oe.smi in the current directory.
    If you can't find the file, grab it from the RCSB
    :return: Ligand Expo as a dictionary with ligand id as the key
    """
    file_name = "Components-smiles-stereo-oe.smi"
    try:
        df = pd.read_csv(file_name, sep="\t",
                         header=None,
                         names=["SMILES", "ID", "Name"])
    except FileNotFoundError:
        url = f"http://ligand-expo.rcsb.org/dictionaries/{file_name}"
        print(url)
        r = requests.get(url, allow_redirects=True)
        open('Components-smiles-stereo-oe.smi', 'wb').write(r.content)
        df = pd.read_csv(file_name, sep="\t",
                         header=None,
                         names=["SMILES", "ID", "Name"])
    df.set_index("ID", inplace=True)
    return df.to_dict()


def get_pdb_components(pdb_id):
    """
    Split a protein-ligand pdb into protein and ligand components
    :param pdb_id:
    :return:
    """
    with gzip.open(pdb_id,'rt') as f:
        pdb = parsePDBStream(f)

    protein = pdb.select('protein')
    ligand = pdb.select('not protein and not water')
    return protein, ligand


def process_ligand(ligand, res_name, expo_dict):
    """
    Add bond orders to a pdb ligand
    1. Select the ligand component with name "res_name"
    2. Get the corresponding SMILES from the Ligand Expo dictionary
    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
    :param expo_dict: dictionary with LigandExpo
    :return: molecule with bond orders assigned
    """
    output = StringIO()
    sub_mol = ligand.select(f"resname {res_name}")
    sub_smiles = expo_dict['SMILES'][res_name]
    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, template

def process_entry(df_dict, pdb_fn):
    try:
        """
        Slit pdb into protein and ligands,
        parse protein sequence and ligand tokens
        :param df_dict: ligand expo data
        :param pdb_fn: pdb entry file name
        :return:
        """
        protein, ligand = get_pdb_components(pdb_fn)

        ligand_mols = []
        ligand_names = []

        if ligand is not None:
            # filter ligands by molecular weight
            res_name_list = list(set(ligand.getResnames()))
            for res in res_name_list:
                mol, template = process_ligand(ligand, res, df_dict)

                mol_wt = ExactMolWt(template)

                if mol_wt >= mol_wt_cutoff:
                    ligand_mols.append(mol)
                    ligand_names.append(res)

        ligand_smiles = []
        ligand_xyz = []

        pdb_name = os.path.basename(pdb_fn).split('.')[-3][3:]
        for mol, name in zip(ligand_mols, ligand_names):
            print('Processing {} and {}'.format(pdb_name, name))
            smi, xyz = tokenize_ligand(mol)
            ligand_smiles.append(smi)
            ligand_xyz.append(xyz)

        seq, receptor_xyz = get_protein_sequence_and_coords(protein)
        return pdb_name, seq, receptor_xyz, ligand_names, ligand_smiles, ligand_xyz
    except Exception as e:
        print(repr(e))

if __name__ == '__main__':
    import glob

    filenames = glob.glob('pdb/*/*.gz')
    filenames = sorted(filenames)
    comm = MPI.COMM_WORLD
    with MPICommExecutor(comm, root=0) as executor:
#    with MPIPoolExecutor() as executor:
        if executor is not None:
            # read ligand table
            df_dict = read_ligand_expo()

            result = executor.map(partial(process_entry, df_dict), filenames, chunksize=512)
            result = list(result)

            # expand sequences and ligands
            pdb_id = [r[0] for r in result if r is not None for ligand in r[3]]
            seq = [r[1] for r in result if r is not None for ligand in r[3]]
            receptor_xyz = [r[2] for r in result if r is not None for ligand in r[3]]
            lig_id = [l for r in result if r is not None for l in r[3]]
            lig_smiles = [s for r in result if r is not None for s in r[4]]
            lig_xyz = [xyz for r in result if r is not None for xyz in r[5]]

            import pandas as pd
            df = pd.DataFrame({'pdb_id': pdb_id, 'lig_id': lig_id, 'seq': seq, 'smiles': lig_smiles, 'receptor_xyz': receptor_xyz, 'ligand_xyz': lig_xyz})
            df.to_parquet('data/pdb.parquet',index=False)