Release 1.3.0

CHANGELOG.md

@@ -1,5 +1,20 @@
 # CHANGELOG
 
+## Version 1.3.0 - 2024-01-09
+
+### Features
+
+- Adding support for Condensed Graph of Reaction
+- Adding support for flagging stereocontrolled reactions
+- Adding routines for desalting reactions
+- Adding routines for identifying reaction centers
+- Adding several dataframe modifying actions
+- Adding several reaction modifying actions
+
+### Trival changes
+
+- Unifying routines to make and concatenate batches
+
 ## Version 1.2.0 - 2022-11-21
 
 ### Features

README.md

@@ -106,6 +106,8 @@ Please use ``black`` package for formatting, and follow ``pep8`` style guide.
 
 * [@ckannas](https://github.com/ckannas)
 * [@SGenheden](https://www.github.com/SGenheden)
+* [@anniewesterlund](https://www.github.com/anniewesterlund) 
+* [@CBA087](https://www.github.com/CBA087) 
 * [@EBjerrum](https://www.github.com/EBjerrum)
 * [@A-Thakkar](https://www.github.com/A-Thakkar)
 

docs/conf.py

@@ -6,7 +6,7 @@
 project = "ReactionUtils"
 copyright = "2022, Molecular AI group"
 author = "Molecular AI group"
-release = "1.2.0"
+release = "1.3.0"
 
 extensions = [
     "sphinx.ext.autodoc",

env-dev.yml

@@ -3,5 +3,5 @@ channels:
   - https://conda.anaconda.org/conda-forge
   - defaults
 dependencies:
-  - python>=3.8,<3.10
+  - python>=3.9,<3.11
   - poetry>=1.1.4,<2.0

pyproject.toml

@@ -1,6 +1,6 @@
 [tool.poetry]
 name = "reaction_utils"
-version = "1.2.0"
+version = "1.3.0"
 description = "Utilities for working with reactions, reaction templates and template extraction"
 authors = ["Genheden, Samuel <[email protected]>", "Kannas, Christos <[email protected]>"]
 license = "Apache-2.0"
@@ -13,18 +13,20 @@ packages = [
 ]
 
 [tool.poetry.dependencies]
-python = "^3.8"
+python = ">=3.9,<3.11"
+urllib3 = "<2.0"
 pandas = "^1.0.0"
 xxhash = "^2.0.0"
 rdchiral = "^1.1.0" 
-PyYAML = "^5.4.1"
+PyYAML = "^6.0.1"
 swifter = "^1.0.9"
 metaflow = "^2.6.3"
 py7zr = "^0.18.7"
 Deprecated = "^1.2.13"
-Sphinx = "^5.0.1"
 wrapt-timeout-decorator = "^1.3.12"
 rdkit = "^2022.3.3"
+cgrtools = "^4.1.35"
+scipy = "^1.11.4"
 
 [tool.poetry.dev-dependencies]
 pytest = "^6.2.2"
@@ -39,6 +41,7 @@ pre-commit = "^2.10.1"
 ipython = "^7.21.0"
 pylint = "^2.14.1"
 invoke = "^1.7.1"
+sphinx = "^4.0.0"
 
 [build-system]
 requires = ["poetry-core>=1.0.0"]

rxnutils/chem/cgr.py

@@ -0,0 +1,141 @@
+""" Wrapper class for the CGRTools library
+"""
+import io
+import warnings
+from typing import List
+
+from CGRtools.files.SDFrw import SDFRead
+from CGRtools.containers.reaction import ReactionContainer
+from CGRtools.containers.molecule import MoleculeContainer
+from rdkit import Chem
+
+from rxnutils.chem.reaction import ChemicalReaction
+from rxnutils.chem.utils import atom_mapping_numbers
+
+
+class CondensedGraphReaction:
+    """
+    The Condensed Graph of Reaction (CGR) representation of a reaction
+
+    :ivar reaction_container: the CGRTools container of the reaction
+    :ivar cgr_container: the CGRTools container of the CGR
+    :param reaction: the reaction composed of RDKit molecule to start from
+    :raises ValueError: if it is not possible to create the CGR from the reaction
+    """
+
+    def __init__(self, reaction: ChemicalReaction) -> None:
+        self.reaction = reaction
+        self._cgr_reactants = []
+        self._cgr_products = []
+        self._make_cgr_containers()
+        self.reaction_container = ReactionContainer(
+            reactants=self._cgr_reactants, products=self._cgr_products
+        )
+        try:
+            self.cgr_container = self.reaction_container.compose()
+        except ValueError as err:
+            if str(err) == "mapping of graphs is not disjoint":
+                raise ValueError(
+                    "Reaction contains inconsistent atom-mapping, perhaps duplicates"
+                )
+            elif str(err).endswith("} not equal"):
+                raise ValueError(
+                    "Atom with the same atom-mapping in reactant and product is not equal"
+                )
+            else:
+                raise ValueError(f"Unknown problem with generating CGR: {err}")
+
+    def __eq__(self, obj: object) -> bool:
+        if not isinstance(obj, CondensedGraphReaction):
+            return False
+        return self.cgr_container == obj.cgr_container
+
+    @property
+    def bonds_broken(self) -> int:
+        """Returns the number of broken bonds in the reaction"""
+        return sum(bond.p_order is None for _, _, bond in self.cgr_container.bonds())
+
+    @property
+    def bonds_changed(self) -> int:
+        """Returns the number of broken or formed bonds in the reaction"""
+        return sum(
+            bond.p_order is None or bond.order is None
+            for _, _, bond in self.cgr_container.bonds()
+        )
+
+    @property
+    def bonds_formed(self) -> int:
+        """Returns the number of formed bonds in the reaction"""
+        return sum(bond.order is None for _, _, bond in self.cgr_container.bonds())
+
+    @property
+    def total_centers(self) -> int:
+        """Returns the number of atom and bond centers in the reaction"""
+        return len(self.cgr_container.center_atoms) + len(
+            self.cgr_container.center_bonds
+        )
+
+    def distance_to(self, other: "CondensedGraphReaction") -> int:
+        """
+        Returns the chemical distance between two reactions, i.e. the absolute difference
+        between the total number of centers.
+
+        Used for some atom-mapping comparison statistics
+
+        :param other: the reaction to compare to
+        :returns: the computed distance
+        """
+        return abs(self.total_centers - other.total_centers)
+
+    def _make_cgr_containers(self):
+        nreactants = len(self.reaction.reactants)
+        renumbered_mols = self._make_renumbered_mols()
+        self._cgr_reactants = _convert_rdkit_molecules(renumbered_mols[:nreactants])
+        self._cgr_products = _convert_rdkit_molecules(renumbered_mols[nreactants:])
+
+        if len(self._cgr_reactants) != nreactants:
+            warnings.warn("Warning not all reactants could be converted to CGRtools")
+        if len(self._cgr_products) != len(self.reaction.products):
+            warnings.warn("Warning not all products could be converted to CGRtools")
+
+    def _make_renumbered_mols(self):
+        # It is necessary that all atoms have atom-mapping
+        # otherwise CGRTools will start adding bad atom-mappings
+        # so this adds safe atom-mapping to un-mapped atoms
+        renumbered_mols = []
+        max_atom_map_numb = max(
+            max(atom_mapping_numbers(smi) or [0])
+            for smi in self.reaction.reactants_list + self.reaction.products_list
+        )
+        for mol0 in self.reaction.reactants + self.reaction.products:
+            if mol0 is None:
+                raise ValueError(
+                    "Cannot create CGR for this reaction, some molecules are None"
+                )
+            mol = Chem.rdchem.Mol(mol0)
+            for atom in mol.GetAtoms():
+                if not atom.GetAtomMapNum():
+                    max_atom_map_numb += 1
+                    atom.SetAtomMapNum(max_atom_map_numb)
+            renumbered_mols.append(mol)
+        return renumbered_mols
+
+
+def _convert_rdkit_molecules(
+    mols: List[Chem.rdchem.Mol],
+) -> List[MoleculeContainer]:
+    # This connects the SDWriter of RDKit with the SDFRead of CGRTools
+    with io.StringIO() as sd_buffer:
+        with Chem.SDWriter(sd_buffer) as sd_writer_obj:
+            for mol in mols:
+                sd_writer_obj.write(mol)
+        sd_buffer.seek(0)
+        with SDFRead(sd_buffer, remap=False) as sd_reader_obj:
+            cgr_molecules = sd_reader_obj.read()
+
+    # This make the aromatization of the molecules, which were
+    # lost when writing to SD format. This is essential to keep
+    # the reactant and product structures as equal as possible
+    for mol in cgr_molecules:
+        mol.thiele()
+    return cgr_molecules

rxnutils/chem/utils.py

@@ -9,6 +9,7 @@
 from rdkit import Chem
 from rdkit.Chem import AllChem
 from rdkit.Chem.MolStandardize import rdMolStandardize
+from rdkit.Chem.SaltRemover import SaltRemover
 
 
 def get_special_groups(mol) -> List[Tuple[Tuple[int, ...], Tuple[int, ...]]]:
@@ -336,14 +337,15 @@ def has_atom_mapping(
 
 
 def remove_atom_mapping(
-    smiles: str, is_smarts: bool = False, sanitize: bool = True
+    smiles: str, is_smarts: bool = False, sanitize: bool = True, canonical: bool = True
 ) -> str:
     """
     Returns a molecule without atom mapping
 
     :param smiles: the SMILES/SMARTS representing the molecule
     :param is_smarts: if True, will interpret the SMILES as a SMARTS
     :param sanitize: if True, will sanitize the molecule
+    :param canonical: if False, will not canonicalize (applies to SMILES)
     :return: the molecule without atom-mapping
     """
     if not smiles:
@@ -358,7 +360,7 @@ def remove_atom_mapping(
     # is_smarts=True: Chem.MolToSmarts
     # is_smarts=False: Chem.MolToSmiles
     to_func = {
-        False: Chem.MolToSmiles,
+        False: functools.partial(Chem.MolToSmiles, canonical=canonical),
         True: Chem.MolToSmarts,
     }
     mol = from_func[is_smarts](smiles)
@@ -368,6 +370,7 @@ def remove_atom_mapping(
 
     for atom in mol.GetAtoms():
         atom.SetAtomMapNum(0)
+
     return to_func[is_smarts](mol)
 
 
@@ -403,6 +406,35 @@ def neutralize_molecules(smiles_list: List[str]) -> List[str]:
     return [Chem.MolToSmiles(mol) for mol in neutral_mols]
 
 
+def desalt_molecules(smiles_list: List[str], keep_something: bool = False) -> List[str]:
+    """
+    Remove salts from a set of molecules using RDKit routines
+
+    :param smiles_list: the molecules as SMILES
+    :param keep_something: if True will keep at least one salt
+    :return: the desalted molecules
+    """
+    remover = SaltRemover()  # use default saltremover
+    mols = [Chem.MolFromSmiles(smi) for smi in smiles_list]
+    desalted_mols = [
+        remover.StripMol(mol, dontRemoveEverything=keep_something)
+        for mol in mols
+        if mol
+    ]
+    if len(mols) > len(desalted_mols):
+        logging.warning(
+            f"No. of desalted molecules ({len(desalted_mols)}) are less than No. of input molecules ({len(mols)})."
+        )
+
+    smiles_list_new = [Chem.MolToSmiles(mol) for mol in desalted_mols]
+    smiles_list_new = [smi for smi in smiles_list_new if smi]
+    if len(smiles_list) > len(smiles_list_new):
+        logging.warning(
+            f"No. of desalted SMILES ({len(smiles_list_new)}) are less than No. of input SMILES ({len(smiles_list)})."
+        )
+    return smiles_list_new
+
+
 def same_molecule(mol1, mol2) -> bool:
     """Test if two molecules are the same.
     First number of atoms and bonds are compared to guard the potentially more expensive
@@ -501,6 +533,17 @@ def reassign_rsmi_atom_mapping(rsmi: str, as_smiles: bool = False) -> str:
     return updated_rsmi
 
 
+def join_smiles_from_reaction(smiles_list: List[str]) -> str:
+    """
+    Join a part of reaction SMILES, e.g. reactants and products into components.
+    Intra-molecular complexes are bracketed with parenthesis
+
+    :param smiles_list: the SMILES components
+    :return: the joined list
+    """
+    return ".".join([f"({item})" if "." in item else item for item in smiles_list])
+
+
 def split_smiles_from_reaction(smiles: str) -> List[str]:
     """
     Split a part of reaction SMILES, e.g. reactants or products
@@ -540,3 +583,73 @@ def split_smiles_from_reaction(smiles: str) -> List[str]:
         else:
             components.append(smiles[block_start:pos])
     return components
+
+
+def reaction_centres(rxn: AllChem.ChemicalReaction) -> Tuple[List[int], ...]:
+    """
+    Return reaction centre atoms, provided that the bonding partners
+    actually change when comparing the environment in the reactant and the product
+
+    inspired by code from Greg Landrum's tutorial
+    set up array to remove atoms from the reaction centers
+    by comparing the atom mapping in the reactant vs the products
+
+    Original implementation by Christoph Bauer
+
+    :param rxn: the initialized RDKit reaction
+    :return: tuple of reaction centre atoms, filtered by connectivity criterion
+    """
+    rxncenters = rxn.GetReactingAtoms(mappedAtomsOnly=True)
+
+    remove_array = []
+    nreactants = len(rxncenters)
+    for ridx, reacting in enumerate(rxncenters):
+        reactant = rxn.GetReactantTemplate(ridx)
+        for raidx in reacting:
+            ratm = reactant.GetAtomWithIdx(raidx)
+            mapnum = ratm.GetAtomMapNum()
+            numexplicitH_reactant = ratm.GetNumExplicitHs()
+            neighbours = ratm.GetNeighbors()
+            map_neighbours = sorted(
+                [neighbour_atom.GetAtomMapNum() for neighbour_atom in neighbours]
+            )
+            foundit = False
+            for product in rxn.GetProducts():
+                for patom in product.GetAtoms():
+                    if patom.GetAtomMapNum() == mapnum:
+                        neighbours_product = patom.GetNeighbors()
+                        numexplicitH_product = patom.GetNumExplicitHs()
+                        map_neighbours_product = sorted(
+                            [
+                                neighbour_atom.GetAtomMapNum()
+                                for neighbour_atom in neighbours_product
+                            ]
+                        )
+                        # criterion: check if the map numbers of neighbours are the same in the reactant and the product
+                        if map_neighbours == map_neighbours_product:
+                            if numexplicitH_reactant == numexplicitH_product:
+                                # if yes --> then the environment doesn't change, so set remove to True
+                                remove_array.append(True)
+                            else:
+                                remove_array.append(False)
+                        else:
+                            # False means that the environment does change, so set remove to False
+                            remove_array.append(False)
+                        foundit = True
+                        break
+                    if foundit:
+                        break
+
+    # actual removal of reaction centres by generating new tuple
+    rxncenters_filtered = []
+    counter = 0
+    for reactant_idx in range(nreactants):
+        reactantcenters = []
+        for index in rxncenters[reactant_idx]:
+            if not remove_array[counter]:
+                reactantcenters.append(index)
+            counter += 1
+        reactantcenters = tuple(reactantcenters)
+        rxncenters_filtered.append(reactantcenters)
+    rxncenters_filtered = tuple(rxncenters_filtered)
+    return rxncenters_filtered