Reaction.h

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#include <RDGeneral/export.h>
#ifndef RD_REACTION_H_17Aug2006
#define RD_REACTION_H_17Aug2006
 
#include <GraphMol/RDKitBase.h>
#include <RDGeneral/RDProps.h>
#include <GraphMol/Substruct/SubstructMatch.h>
#include <string_view>
#include <vector>
 
namespace RDKit {
class ReactionPickler;
 
//! used to indicate an error in the chemical reaction engine
class RDKIT_CHEMREACTIONS_EXPORT ChemicalReactionException
    : public std::exception {
 public:
  //! construct with an error message
  explicit ChemicalReactionException(const char *msg) : _msg(msg) {}
  //! construct with an error message
  explicit ChemicalReactionException(const std::string msg) : _msg(msg) {}
  //! get the error message
  const char *what() const noexcept override { return _msg.c_str(); }
  ~ChemicalReactionException() noexcept override = default;
 
 private:
  std::string _msg;
};
 
//! This is a class for storing and applying general chemical reactions.
/*!
   basic usage will be something like:
 
   \verbatim
   ChemicalReaction rxn;
   rxn.addReactantTemplate(r1);
   rxn.addReactantTemplate(r2);
   rxn.addProductTemplate(p1);
   rxn.initReactantMatchers();
 
   MOL_SPTR_VECT prods;
   for(MOL_SPTR_VECT::const_iterator r1It=reactantSet1.begin();
       r1It!=reactantSet1.end();++r1It;){
     for(MOL_SPTR_VECT::const_iterator r2It=reactantSet2.begin();
         r2It!=reactantSet2.end();++r2It;){
       MOL_SPTR_VECT rVect(2);
       rVect[0] = *r1It;
       rVect[1] = *r2It;
 
       std::vector<MOL_SPTR_VECT> lprods;
       lprods = rxn.runReactants(rVect);
       for(std::vector<MOL_SPTR_VECT>::const_iterator lpIt=lprods.begin();
          lpIt!=lprods.end();++lpIt){
          // we know this is a single-product reaction:
          prods.push_back((*lpIt)[0]);
       }
     }
   }
   \endverbatim
 
   NOTES:
     - to allow more control over the reaction, it is possible to flag reactant
       atoms as being protected by setting the common_properties::_protected
   property on those
       atoms. Here's an example:
       \verbatim
          std::string smi="[O:1]>>[N:1]";
          ChemicalReaction *rxn = RxnSmartsToChemicalReaction(smi);
          rxn->initReactantMatchers();
 
          MOL_SPTR_VECT reacts;
          reacts.clear();
          smi = "OCO";
          ROMol *mol = SmilesToMol(smi);
          reacts.push_back(ROMOL_SPTR(mol));
          std::vector<MOL_SPTR_VECT> prods;
          prods = rxn->runReactants(reacts);
          // here prods has two entries, because there are two Os in the
          // reactant.
 
          reacts[0]->getAtomWithIdx(0)->setProp(common_properties::_protected,1);
          prods = rxn->runReactants(reacts);
          // here prods only has one entry, the reaction at atom 0
          // has been blocked by the _protected property
       \endverbatim
 
*/
class RDKIT_CHEMREACTIONS_EXPORT ChemicalReaction : public RDProps {
  friend class ReactionPickler;
 
 private:
  void copy(const ChemicalReaction &other) {
    RDProps::operator=(other);
    df_needsInit = other.df_needsInit;
    df_implicitProperties = other.df_implicitProperties;
    m_reactantTemplates.clear();
    m_reactantTemplates.reserve(other.m_reactantTemplates.size());
    for (ROMOL_SPTR reactant_template : other.m_reactantTemplates) {
      m_reactantTemplates.emplace_back(new RWMol(*reactant_template));
    }
    m_productTemplates.clear();
    m_productTemplates.reserve(other.m_productTemplates.size());
    for (ROMOL_SPTR product_template : other.m_productTemplates) {
      m_productTemplates.emplace_back(new RWMol(*product_template));
    }
    m_agentTemplates.clear();
    m_agentTemplates.reserve(other.m_agentTemplates.size());
    for (ROMOL_SPTR agent_template : other.m_agentTemplates) {
      m_agentTemplates.emplace_back(new RWMol(*agent_template));
    }
    d_substructParams = other.d_substructParams;
  }
 
 public:
  ChemicalReaction() : RDProps() {}
  //! construct a reaction from a pickle string
  ChemicalReaction(const std::string &binStr);
  ChemicalReaction(const ChemicalReaction &other) : RDProps() { copy(other); }
  ChemicalReaction &operator=(const ChemicalReaction &other) {
    if (this != &other) {
      copy(other);
    }
    return *this;
  }
 
  //! Adds a new reactant template
  /*!
    \return the number of reactants
 
  */
  unsigned int addReactantTemplate(ROMOL_SPTR mol) {
    this->df_needsInit = true;
    this->m_reactantTemplates.push_back(mol);
    return rdcast<unsigned int>(this->m_reactantTemplates.size());
  }
 
  //! Adds a new agent template
  /*!
    \return the number of agent
 
  */
  unsigned int addAgentTemplate(ROMOL_SPTR mol) {
    this->m_agentTemplates.push_back(mol);
    return rdcast<unsigned int>(this->m_agentTemplates.size());
  }
 
  //! Adds a new product template
  /*!
    \return the number of products
 
  */
  unsigned int addProductTemplate(ROMOL_SPTR mol) {
    this->m_productTemplates.push_back(mol);
    return rdcast<unsigned int>(this->m_productTemplates.size());
  }
 
  //! Removes the reactant templates from a reaction if atom mapping ratio is
  /// below a given threshold
  /*! By default the removed reactant templates were attached to the agent
     templates.
      An alternative will be to provide a pointer to a molecule vector where
     these reactants should be saved.
  */
  void removeUnmappedReactantTemplates(double thresholdUnmappedAtoms = 0.2,
                                       bool moveToAgentTemplates = true,
                                       MOL_SPTR_VECT *targetVector = nullptr);
 
  //! Removes the product templates from a reaction if its atom mapping ratio is
  /// below a given threshold
  /*! By default the removed products templates were attached to the agent
     templates.
      An alternative will be to provide a pointer to a molecule vector where
     these products should be saved.
  */
  void removeUnmappedProductTemplates(double thresholdUnmappedAtoms = 0.2,
                                      bool moveToAgentTemplates = true,
                                      MOL_SPTR_VECT *targetVector = nullptr);
 
  /*! Removes the agent templates from a reaction if a pointer to a
      molecule vector is provided the agents are stored therein.*/
  void removeAgentTemplates(MOL_SPTR_VECT *targetVector = nullptr);
 
  //! Runs the reaction on a set of reactants
  /*!
 
    \param reactants  the reactants to be used. The length of this must be equal
    to this->getNumReactantTemplates()
    \param maxProducts:  if non zero, the maximum number of products to generate
    before stopping.  If hit a warning will be generated.
 
    \return a vector of vectors of products. Each subvector will be
            this->getNumProductTemplates() long.
 
    We return a vector of vectors of products because each individual template
    may map multiple times onto its reactant. This leads to multiple possible
    result sets.
  */
  std::vector<MOL_SPTR_VECT> runReactants(
      const MOL_SPTR_VECT reactants, unsigned int numProducts = 1000) const;
 
  //! Runs a single reactant against a single reactant template
  /*!
     \param reactant The single reactant to use
 
     \param reactantTemplateIdx the reactant template to target in the reaction
  */
  std::vector<MOL_SPTR_VECT> runReactant(
      ROMOL_SPTR reactant, unsigned int reactantTemplateIdx) const;
 
  //! Runs a single reactant in place (the reactant is modified)
  /*!
    This is only useable with reactions which have a single reactant and product
    and where no atoms are added in the product.
 
     \param reactant The single reactant to use
     \param removeUnmatchedAtoms toggles whether or not atoms from the reactant
                             which do not match template atoms are removed.
 
     \return whether or not the reactant was actually modified
  */
  bool runReactant(RWMol &reactant, bool removeUnmatchedAtoms = true) const;
 
  const MOL_SPTR_VECT &getReactants() const {
    return this->m_reactantTemplates;
  }
  const MOL_SPTR_VECT &getAgents() const { return this->m_agentTemplates; }
  const MOL_SPTR_VECT &getProducts() const { return this->m_productTemplates; }
 
  MOL_SPTR_VECT::const_iterator beginReactantTemplates() const {
    return this->m_reactantTemplates.begin();
  }
  MOL_SPTR_VECT::const_iterator endReactantTemplates() const {
    return this->m_reactantTemplates.end();
  }
 
  MOL_SPTR_VECT::const_iterator beginProductTemplates() const {
    return this->m_productTemplates.begin();
  }
  MOL_SPTR_VECT::const_iterator endProductTemplates() const {
    return this->m_productTemplates.end();
  }
 
  MOL_SPTR_VECT::const_iterator beginAgentTemplates() const {
    return this->m_agentTemplates.begin();
  }
  MOL_SPTR_VECT::const_iterator endAgentTemplates() const {
    return this->m_agentTemplates.end();
  }
 
  MOL_SPTR_VECT::iterator beginReactantTemplates() {
    return this->m_reactantTemplates.begin();
  }
  MOL_SPTR_VECT::iterator endReactantTemplates() {
    return this->m_reactantTemplates.end();
  }
 
  MOL_SPTR_VECT::iterator beginProductTemplates() {
    return this->m_productTemplates.begin();
  }
  MOL_SPTR_VECT::iterator endProductTemplates() {
    return this->m_productTemplates.end();
  }
 
  MOL_SPTR_VECT::iterator beginAgentTemplates() {
    return this->m_agentTemplates.begin();
  }
  MOL_SPTR_VECT::iterator endAgentTemplates() {
    return this->m_agentTemplates.end();
  }
  unsigned int getNumReactantTemplates() const {
    return rdcast<unsigned int>(this->m_reactantTemplates.size());
  }
  unsigned int getNumProductTemplates() const {
    return rdcast<unsigned int>(this->m_productTemplates.size());
  }
  unsigned int getNumAgentTemplates() const {
    return rdcast<unsigned int>(this->m_agentTemplates.size());
  }
 
  //! initializes our internal reactant-matching datastructures.
  /*!
      This must be called after adding reactants and before calling
      runReactants.
 
      \param silent: If this bool is true, no messages will be logged during the
      validation. By default, validation problems are reported to the warning
      and error logs depending on their severity.
  */
  void initReactantMatchers(bool silent = false);
 
  bool isInitialized() const { return !df_needsInit; }
 
  //! validates the reactants and products to make sure the reaction seems
  /// "reasonable"
  /*!
      \return   true if the reaction validates without errors (warnings do not
      stop validation)
 
      \param numWarnings used to return the number of validation warnings
      \param numErrors   used to return the number of validation errors
 
      \param silent: If this bool is true, no messages will be logged during the
      validation. By default, validation problems are reported to the warning
      and error logs depending on their severity.
 
  */
  bool validate(unsigned int &numWarnings, unsigned int &numErrors,
                bool silent = false) const;
 
  //! returns whether or not the reaction uses implicit
  //! properties on the product atoms
  /*!
 
    This toggles whether or not unspecified atomic properties in the
    products are considered to be implicit and should be copied from
    the actual reactants. This is necessary due to a semantic difference
    between the "reaction SMARTS" approach and the MDL RXN
    approach:
      In "reaction SMARTS", this reaction:
        [C:1]-[Br:2].[O-:3]>>[C:1]-[O:3].[Br-:2]
      applied to [CH4+]Br should yield [CH4+]O
      Something similar drawn in an rxn file, and applied to
      [CH4+]Br should yield [CH3]O.
      In rxn there is no charge on the product C because nothing is
      specified in the rxn file; in "SMARTS" the charge from the
      actual reactants is not *removed* because no charge is
      specified in the reaction.
 
  */
  bool getImplicitPropertiesFlag() const { return df_implicitProperties; }
  //! sets the implicit properties flag. See the documentation for
  //! getImplicitProertiesFlag() for a discussion of what this means.
  void setImplicitPropertiesFlag(bool val) { df_implicitProperties = val; }
 
  const SubstructMatchParameters &getSubstructParams() const {
    return d_substructParams;
  }
  SubstructMatchParameters &getSubstructParams() { return d_substructParams; }
 
 private:
  bool df_needsInit{true};
  bool df_implicitProperties{false};
  MOL_SPTR_VECT m_reactantTemplates, m_productTemplates, m_agentTemplates;
  SubstructMatchParameters d_substructParams;
};
 
//! tests whether or not the molecule has a substructure match
//! to the reaction's reactants
//! the \c which argument is used to return which of the reactants
//! the molecule matches.
RDKIT_CHEMREACTIONS_EXPORT bool isMoleculeReactantOfReaction(
    const ChemicalReaction &rxn, const ROMol &mol,
    std::vector<unsigned int> &which, bool stopAtFirstMatch = false);
//! \overload
RDKIT_CHEMREACTIONS_EXPORT bool isMoleculeReactantOfReaction(
    const ChemicalReaction &rxn, const ROMol &mol, unsigned int &which);
//! \overload
RDKIT_CHEMREACTIONS_EXPORT bool isMoleculeReactantOfReaction(
    const ChemicalReaction &rxn, const ROMol &mol);
 
//! tests whether or not the molecule has a substructure match
//! to the reaction's products
//! the \c which argument is used to return which of the products
//! the molecule matches.
RDKIT_CHEMREACTIONS_EXPORT bool isMoleculeProductOfReaction(
    const ChemicalReaction &rxn, const ROMol &mol,
    std::vector<unsigned int> &which, bool stopAtFirstMatch = false);
//! \overload
RDKIT_CHEMREACTIONS_EXPORT bool isMoleculeProductOfReaction(
    const ChemicalReaction &rxn, const ROMol &mol, unsigned int &which);
//! \overload
RDKIT_CHEMREACTIONS_EXPORT bool isMoleculeProductOfReaction(
    const ChemicalReaction &rxn, const ROMol &mol);
 
//! tests whether or not the molecule has a substructure match
//! to any of the reaction's agents
//! the \c which argument is used to return which of the agents
//! the molecule matches. If there's no match, it is equal to the number
//! of agents on return
RDKIT_CHEMREACTIONS_EXPORT bool isMoleculeAgentOfReaction(
    const ChemicalReaction &rxn, const ROMol &mol, unsigned int &which);
//! \overload
RDKIT_CHEMREACTIONS_EXPORT bool isMoleculeAgentOfReaction(
    const ChemicalReaction &rxn, const ROMol &mol);
 
//! returns indices of the atoms in each reactant that are changed
//! in the reaction
/*!
  \param rxn the reaction we are interested in
 
  \param mappedAtomsOnly if set, atoms that are not mapped will not be included
  in the list of changed atoms (otherwise they are automatically included)
 
   How are changed atoms recognized?
       1) Atoms whose degree changes
       2) Atoms whose bonding pattern changes
       3) unmapped atoms (unless the mappedAtomsOnly flag is set)
       4) Atoms connected to unmapped atoms
       5) Atoms whose atomic number changes (unless the
          corresponding product atom is a dummy)
       6) Atoms with more than one atomic number query (unless the
          corresponding product atom is a dummy)
 
   Note that the atomic number of a query atom depends on how it's constructed.
     When coming from SMARTS: if the first query is an atomic label/number that
        sets the atomic number, otherwise it's zero.
        For example [O;$(OC)] is atomic number 8 while [$(OC);O] is atomic
        number 0.
     When coming from RXN: the atomic number of the atom in the rxn file sets
        the value.
 */
RDKIT_CHEMREACTIONS_EXPORT VECT_INT_VECT
getReactingAtoms(const ChemicalReaction &rxn, bool mappedAtomsOnly = false);
 
//! add the recursive queries to the reactants of a reaction
/*!
  This does its work using RDKit::addRecursiveQueries()
 
    \param rxn the reaction we are interested in
    \param queries        - the dictionary of named queries to add
    \param propName       - the atom property to use to get query names
    optional:
    \param reactantLabels - to store pairs of (atom index, query string)
                            per reactant
 
    NOTES:
      - existing query information, if present, will be supplemented (AND logic)
      - non-query atoms will be replaced with query atoms using only the query
        logic
      - query names can be present as comma separated lists, they will then
        be combined using OR logic.
      - throws a KeyErrorException if a particular query name is not present
        in \c queries
 
 */
RDKIT_CHEMREACTIONS_EXPORT void addRecursiveQueriesToReaction(
    ChemicalReaction &rxn, const std::map<std::string, ROMOL_SPTR> &queries,
    const std::string_view &propName,
    std::vector<std::vector<std::pair<unsigned int, std::string>>>
        *reactantLabels = nullptr);
 
}  // namespace RDKit
 
namespace RDDepict {
//! \brief Generate 2D coordinates (a depiction) for a reaction
/*!
 
  \param rxn the reaction we are interested in
 
  \param spacing the spacing between components of the reaction
 
  \param updateProps if set, properties such as conjugation and
      hybridization will be calculated for the reactant and product
      templates before generating coordinates. This should result in
      better depictions, but can lead to errors in some cases.
 
  \param canonOrient canonicalize the orientation so that the long
  axes align with the x-axis etc.
 
  \param nFlipsPerSample - the number of rotatable bonds that are
  flipped at random for each sample
 
  \param nSamples - the number of samples
 
  \param sampleSeed - seed for the random sampling process
 
  \param permuteDeg4Nodes - try permuting the drawing order of bonds around
        atoms with four neighbors in order to improve the depiction
 
  for the other parameters see the documentation for compute2DCoords()
 
*/
RDKIT_CHEMREACTIONS_EXPORT void compute2DCoordsForReaction(
    RDKit::ChemicalReaction &rxn, double spacing = 1.0, bool updateProps = true,
    bool canonOrient = false, unsigned int nFlipsPerSample = 0,
    unsigned int nSamples = 0, int sampleSeed = 0,
    bool permuteDeg4Nodes = false);
 
}  // namespace RDDepict
 
#endif