Source code for schrodinger.livedesign.substructure

"""
Substructure searching and alignment

Copyright Schrodinger LLC, All Rights Reserved.
"""

from typing import Generator
from typing import NamedTuple
from typing import Optional

from rdkit import Chem
from rdkit.Chem import rdDepictor
from rdkit.Chem import rdMolEnumerator
from rdkit.Chem import rdTautomerQuery

NO_MATCH_ERROR_MSG = "Substructure match with reference not found"


class QueryOptions(NamedTuple):
    """
    :cvar adjust_conjugated_five_rings: whether to set bond queries in
        conjugated five-member rings to SINGLE|DOUBLE|AROMATIC
    :cvar adjust_single_bonds_between_aromatic_atoms: whether to sets
        non-ring single bonds between two aromatic atoms to SINGLE|AROMATIC
    :cvar adjust_single_bonds_to_degree_one_neighbors: whether to set single
        bonds bewteen aromatic atoms and degree-one neighbors to SINGLE|AROMATIC
    :cvar tautomer_insensitive: whether to consider tautomer insensitivity
    :cvar stereospecific: whether to consider stereochemistry and chirality
    """

    adjust_conjugated_five_rings: bool = False
    adjust_single_bonds_between_aromatic_atoms: bool = False
    adjust_single_bonds_to_degree_one_neighbors: bool = False
    tautomer_insensitive: bool = False
    stereospecific: bool = True


def expand_query(
        base_query: Chem.rdchem.Mol,
        options: QueryOptions) -> Generator[Chem.rdchem.Mol, None, None]:
    """
    Expands a given query, accounting for tautomer matching, link nodes, and
    variable bonds. If the substructure options dictate it, each  generated
    query is also adjusted.
    """
    options = options or QueryOptions()
    query_params = Chem.AdjustQueryParameters.NoAdjustments()
    query_params.adjustConjugatedFiveRings = \
        options.adjust_conjugated_five_rings
    query_params.adjustSingleBondsBetweenAromaticAtoms = \
        options.adjust_single_bonds_between_aromatic_atoms
    query_params.adjustSingleBondsToDegreeOneNeighbors = \
        options.adjust_single_bonds_to_degree_one_neighbors
    query_params.makeDummiesQueries = True

    query_mols = rdMolEnumerator.Enumerate(base_query) or [base_query]
    for mol in query_mols:
        if options.tautomer_insensitive:
            # initialize RingInfo
            Chem.FastFindRings(mol)
            tqry = rdTautomerQuery.TautomerQuery(mol)
            query = tqry.GetTemplateMolecule()
        else:
            query = mol
        query = Chem.AdjustQueryProperties(query, query_params)
        query.UpdatePropertyCache()
        yield query


def substructure_matches(mol: Chem.rdchem.Mol,
                         query_mol: Chem.rdchem.Mol,
                         options: Optional[QueryOptions] = None):
    """
    Generates all substructure matches against a given query mol
    """
    options = options or QueryOptions()
    params = Chem.rdchem.SubstructMatchParameters()
    params.useChirality = options.stereospecific
    params.useEnhancedStereo = options.stereospecific
    for query in expand_query(query_mol, options):
        yield from mol.GetSubstructMatches(query, params)


def apply_substructure_coordinates(mol: Chem.rdchem.Mol,
                                   template_mol: Chem.rdchem.Mol,
                                   options: Optional[QueryOptions] = None):
    """
    Applies coordinates from the provided template to the input mol; used for
    compound alignment requests in image generation.

    NOTE: If the substructure match to the template fails, the alignment is
    skipped altogether, leaving the input mol coordinates as they were
    """
    options = options or QueryOptions()
    template_mol = next(expand_query(template_mol, options))
    params = Chem.rdchem.SubstructMatchParameters()
    params.useChirality = options.stereospecific
    params.useEnhancedStereo = options.stereospecific
    if not mol.HasSubstructMatch(template_mol, params):
        return
    rdDepictor.GenerateDepictionMatching2DStructure(mol, template_mol)