ChEMBLStandardizer.hpp

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/* 
 * ChEMBLStandardizer.hpp 
 *
 * Implementation of the ChEMBL molecule standardization and parent compound extraction procedure
 * (A. P. Bento et al., An open source chemical structure curation pipeline using RDKit, J. Cheminformatics 2020, 12, 51) 
 *
 * This file is part of the Chemical Data Processing Toolkit
 *
 * Copyright (C) 2003 Thomas Seidel <thomas.seidel@univie.ac.at>
 *
 * This library is free software; you can redistribute it and/or
 * modify it under the terms of the GNU Lesser General Public
 * License as published by the Free Software Foundation; either
 * version 2 of the License, or (at your option) any later version.
 *
 * This library is distributed in the hope that it will be useful,
 * but WITHOUT ANY WARRANTY; without even the implied warranty of
 * MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU
 * Lesser General Public License for more details.
 *
 * You should have received a copy of the GNU Lesser General Public License
 * along with this library; see the file COPYING. If not, write to
 * the Free Software Foundation, Inc., 59 Temple Place - Suite 330,
 * Boston, MA 02111-1307, USA.
 */
 
#ifndef CDPL_CHEM_CHEMBLSTANDARDIZER_HPP
#define CDPL_CHEM_CHEMBLSTANDARDIZER_HPP
 
#include <vector>
#include <cstdint>
#include <utility>
#include <unordered_set>
#include <memory>
 
#include <boost/functional/hash.hpp>
 
#include "CDPL/Chem/APIPrefix.hpp"
#include "CDPL/Chem/BasicMolecule.hpp"
#include "CDPL/Chem/Fragment.hpp"
#include "CDPL/Chem/KekuleStructureCalculator.hpp"
#include "CDPL/Chem/SubstructureSearch.hpp"
#include "CDPL/Chem/HashCodeCalculator.hpp"
#include "CDPL/Chem/ProtonationStateStandardizer.hpp"
#include "CDPL/Util/BitSet.hpp"
#include "CDPL/Math/VectorArray.hpp"
 
 
namespace CDPL
{
 
    namespace Chem
    {
 
        class CDPL_CHEM_API ChEMBLStandardizer
        {
 
          public:
            typedef std::shared_ptr<ChEMBLStandardizer> SharedPointer;
 
            enum ChangeFlags
            {
 
                NONE = 0x0,
 
                EXCLUDED = 0x1,
 
                EXPLICIT_HYDROGENS_REMOVED = 0x2,
 
                UNKNOWN_STEREO_STANDARDIZED = 0x4,
 
                BONDS_KEKULIZED = 0x8,
 
                STRUCTURE_NORMALIZED = 0x10,
 
                CHARGES_REMOVED = 0x20,
 
                TARTRATE_STEREO_CLEARED = 0x40,
 
                STRUCTURE_2D_CORRECTED = 0x80,
 
                ISOTOPE_INFO_CLEARED = 0x100,
 
                SALT_COMPONENTS_REMOVED = 0x200,
 
                SOLVENT_COMPONENTS_REMOVED = 0x400,
 
                DUPLICATE_COMPONENTS_REMOVED = 0x800
            };
 
            ChEMBLStandardizer();
 
            ChEMBLStandardizer(const ChEMBLStandardizer& standardizer);
 
            ChangeFlags standardize(Molecule& mol, bool proc_excld = false);
 
            ChangeFlags standardize(const MolecularGraph& molgraph, Molecule& std_mol, bool proc_excluded = false);
 
            ChangeFlags getParent(Molecule& mol, bool neutralize = true, bool check_exclusion = true);
 
            ChangeFlags getParent(const MolecularGraph& molgraph, Molecule& parent_mol, bool neutralize = true, bool check_exclusion = true);
 
            ChEMBLStandardizer& operator=(const ChEMBLStandardizer& standardizer);
 
          private:
            typedef std::vector<Atom*> AtomList;
 
            void copyMolecularGraph(const MolecularGraph& molgraph, Molecule& mol_copy) const;
 
            bool checkExclusionCriterions(const Molecule& mol) const;
            bool checkExclusionCriterions(const MolecularGraph& molgraph, std::size_t& boron_cnt) const;
 
            bool standardizeUnknownStereochemistry(Molecule& mol) const;
 
            bool kekulizeBonds(Molecule& mol);
 
            bool removeExplicitHydrogens(Molecule& mol) const;
            bool isRemovableHydrogen(const Atom& atom) const;
 
            bool              normalizeStructure(Molecule& mol);
            const Chem::Atom* getAtomWithMappingID(const Molecule& ptn, std::size_t id) const;
 
            bool removeCharges(Molecule& mol);
 
            bool removeTartrateStereochemistry(Molecule& mol);
 
            bool   cleanup2DStructure(Molecule& mol);
            double calc2DBondAngle(const Molecule& mol, const Atom& ctr_atom, const Atom& nbr_atom1, const Atom& nbr_atom2);
            void   rotateSubstituent(const Molecule& mol, const Atom& ctr_atom, const Atom& subst_atom, double rot_ang);
 
            void clearMatchConstraints(Molecule& mol) const;
 
            typedef std::pair<std::uint64_t, std::uint64_t>                    StructureID;
            typedef std::pair<const Fragment*, StructureID>                    MoleculeComponent;
            typedef std::vector<MoleculeComponent>                             MoleculeComponentList;
            typedef std::unordered_set<StructureID, boost::hash<StructureID> > StructureIDSet;
 
            HashCodeCalculator           hashCodeCalc;
            KekuleStructureCalculator    kekuleStructureCalc;
            Util::STArray                kekulizedBondOrders;
            SubstructureSearch           substructSearch;
            ProtonationStateStandardizer chargeStandardizer;
            Math::Vector2DArray          atom2DCoords;
            Util::BitSet                 markedAtomSet;
            Fragment                     tmpFragment;
            BasicMolecule                tmpMolecule;
            MoleculeComponentList        molCompList1;
            MoleculeComponentList        molCompList2;
            StructureIDSet               uniqueMolComps;
        };
    } // namespace Chem
} // namespace CDPL
 
#endif // CDPL_CHEM_CHEMBLSTANDARDIZER_HPP