// $Id$
//
//  Copyright (c) 2007-2014, Novartis Institutes for BioMedical Research Inc.
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// 
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// met: 
//
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#include <GraphMol/ChemReactions/Reaction.h>
#include <GraphMol/ChemReactions/ReactionPickler.h>
#include <GraphMol/Substruct/SubstructMatch.h>
#include <GraphMol/QueryOps.h>
#include <boost/dynamic_bitset.hpp>
#include <boost/foreach.hpp>
#include <map>
#include <algorithm>
#include <GraphMol/ChemTransforms/ChemTransforms.h>
#include <GraphMol/Descriptors/MolDescriptors.h>
#include <GraphMol/SmilesParse/SmilesWrite.h>
#include <GraphMol/ChemReactions/ReactionUtils.h>
#include "GraphMol/ChemReactions/ReactionRunner.h"

namespace RDKit {
  
  std::vector<MOL_SPTR_VECT> ChemicalReaction::runReactants(const MOL_SPTR_VECT reactants) const {
	  return run_Reactants(*this, reactants);
  }

  ChemicalReaction::ChemicalReaction(const std::string &pickle) {
    ReactionPickler::reactionFromPickle(pickle,this);
  }
  
  void ChemicalReaction::initReactantMatchers() {
    unsigned int nWarnings,nErrors;
    if(!this->validate(nWarnings,nErrors)){
      BOOST_LOG(rdErrorLog)<<"initialization failed\n";
      this->df_needsInit=true;
    } else {
      this->df_needsInit=false;
    }
  }

  bool ChemicalReaction::validate(unsigned int &numWarnings,
                                  unsigned int &numErrors,
                                  bool silent) const {
    bool res=true;
    numWarnings=0;
    numErrors=0;
    
    if(!this->getNumReactantTemplates()){
      if(!silent){
        BOOST_LOG(rdErrorLog)<<"reaction has no reactants\n";
      }
      numErrors++;
      res=false;
    }
    
    if(!this->getNumProductTemplates()){
      if(!silent){
        BOOST_LOG(rdErrorLog)<<"reaction has no products\n";
      }
      numErrors++;
      res=false;
    }
    
    std::vector<int> mapNumbersSeen;
    std::map<int,const Atom *> reactingAtoms;
    unsigned int molIdx=0;
    for(MOL_SPTR_VECT::const_iterator molIter=this->beginReactantTemplates();
        molIter!=this->endReactantTemplates();++molIter){
      bool thisMolMapped=false;
      for(ROMol::AtomIterator atomIt=(*molIter)->beginAtoms();
          atomIt!=(*molIter)->endAtoms();++atomIt){
	    int mapNum;
        if((*atomIt)->getPropIfPresent(common_properties::molAtomMapNumber, mapNum)){
          thisMolMapped=true;
          if(std::find(mapNumbersSeen.begin(),mapNumbersSeen.end(),mapNum)!=mapNumbersSeen.end()){
            if(!silent){
              BOOST_LOG(rdErrorLog)<<"reactant atom-mapping number "<<mapNum<<" found multiple times.\n";
            }
            numErrors++;
            res=false;
          } else {
            mapNumbersSeen.push_back(mapNum);
            reactingAtoms[mapNum]=*atomIt;
          }
        }
      }
      if(!thisMolMapped){
        if(!silent){
          BOOST_LOG(rdWarningLog)<<"reactant "<<molIdx<<" has no mapped atoms.\n";
        }
        numWarnings++;
      }
      molIdx++;
    }

    std::vector<int> productNumbersSeen;  
    molIdx=0;
    for(MOL_SPTR_VECT::const_iterator molIter=this->beginProductTemplates();
        molIter!=this->endProductTemplates();++molIter){

      // clear out some possible cached properties to prevent
      // misleading warnings
      for(ROMol::AtomIterator atomIt=(*molIter)->beginAtoms();
          atomIt!=(*molIter)->endAtoms();++atomIt){
        if((*atomIt)->hasProp(common_properties::_QueryFormalCharge))
          (*atomIt)->clearProp(common_properties::_QueryFormalCharge);
        if((*atomIt)->hasProp(common_properties::_QueryHCount))
          (*atomIt)->clearProp(common_properties::_QueryHCount);
        if((*atomIt)->hasProp(common_properties::_QueryMass))
          (*atomIt)->clearProp(common_properties::_QueryMass);
        if((*atomIt)->hasProp(common_properties::_QueryIsotope))
          (*atomIt)->clearProp(common_properties::_QueryIsotope);
      }
      bool thisMolMapped=false;
      for(ROMol::AtomIterator atomIt=(*molIter)->beginAtoms();
          atomIt!=(*molIter)->endAtoms();++atomIt){
	    int mapNum;
        if((*atomIt)->getPropIfPresent(common_properties::molAtomMapNumber, mapNum)){
          thisMolMapped=true;
          bool seenAlready=std::find(productNumbersSeen.begin(),
                                     productNumbersSeen.end(),mapNum)!=productNumbersSeen.end();
          if(seenAlready){
            if(!silent){
              BOOST_LOG(rdWarningLog)<<"product atom-mapping number "<<mapNum<<" found multiple times.\n";
            }
            numWarnings++;
            // ------------
            //   Always check to see if the atoms connectivity changes independent if it is mapped multiple times
            // ------------
            const Atom *rAtom=reactingAtoms[mapNum];
            CHECK_INVARIANT(rAtom,"missing atom");
            if(rAtom->getDegree()!=(*atomIt)->getDegree()){
              (*atomIt)->setProp(common_properties::_ReactionDegreeChanged,1);
            }

          } else {
            productNumbersSeen.push_back(mapNum);
          }
          std::vector<int>::iterator ivIt=std::find(mapNumbersSeen.begin(),
                                                    mapNumbersSeen.end(),mapNum);
          if(ivIt==mapNumbersSeen.end()){
            if(!seenAlready){
              if(!silent){
                BOOST_LOG(rdWarningLog)<<"product atom-mapping number "<<mapNum<<" not found in reactants.\n";
              }
              numWarnings++;
            }
          } else {
            mapNumbersSeen.erase(ivIt); 

            // ------------
            //   The atom is mapped, check to see if its connectivity changes
            // ------------
            const Atom *rAtom=reactingAtoms[mapNum];
            CHECK_INVARIANT(rAtom,"missing atom");
            if(rAtom->getDegree()!=(*atomIt)->getDegree()){
              (*atomIt)->setProp(common_properties::_ReactionDegreeChanged,1);
            }
          }
        }

        // ------------
        //    Deal with queries
        // ------------
        if((*atomIt)->hasQuery()){
          std::list<const Atom::QUERYATOM_QUERY *>queries;
          queries.push_back((*atomIt)->getQuery());
          while(!queries.empty()){
            const Atom::QUERYATOM_QUERY *query=queries.front();
            queries.pop_front();
            for(Atom::QUERYATOM_QUERY::CHILD_VECT_CI qIter=query->beginChildren();
                qIter!=query->endChildren();++qIter){
              queries.push_back((*qIter).get());
            }
            if(query->getDescription()=="AtomFormalCharge"){
              if((*atomIt)->hasProp(common_properties::_QueryFormalCharge)){
                if(!silent){
                  BOOST_LOG(rdWarningLog)<<"atom "<<(*atomIt)->getIdx()<<" in product " 
                                         << molIdx << " has multiple charge specifications.\n";
                }
                numWarnings++;
              } else {
                (*atomIt)->setProp(common_properties::_QueryFormalCharge,
                                   ((const ATOM_EQUALS_QUERY *)query)->getVal());
              }
            } else if(query->getDescription()=="AtomHCount"){
              if((*atomIt)->hasProp(common_properties::_QueryHCount)){
                if(!silent){
                  BOOST_LOG(rdWarningLog)<<"atom "<<(*atomIt)->getIdx()<<" in product " 
                                         << molIdx << " has multiple H count specifications.\n";
                }
                numWarnings++;
              } else {
                (*atomIt)->setProp(common_properties::_QueryHCount,
                                   ((const ATOM_EQUALS_QUERY *)query)->getVal());
              }
            } else if(query->getDescription()=="AtomMass"){
              if((*atomIt)->hasProp(common_properties::_QueryMass)){
                if(!silent) {
                  BOOST_LOG(rdWarningLog)<<"atom "<<(*atomIt)->getIdx()<<" in product " 
                                         << molIdx << " has multiple mass specifications.\n";
                }
                numWarnings++;
              } else {
                (*atomIt)->setProp(common_properties::_QueryMass,
                                   ((const ATOM_EQUALS_QUERY *)query)->getVal()/massIntegerConversionFactor);
              }
            } else if(query->getDescription()=="AtomIsotope"){
              if((*atomIt)->hasProp(common_properties::_QueryIsotope)){
                if(!silent) {
                  BOOST_LOG(rdWarningLog)<<"atom "<<(*atomIt)->getIdx()<<" in product " 
                                         << molIdx << " has multiple isotope specifications.\n";
                }
                numWarnings++;
              } else {
                (*atomIt)->setProp(common_properties::_QueryIsotope,
                                   ((const ATOM_EQUALS_QUERY *)query)->getVal());
              }
            }
          }
        }
      }
      if(!thisMolMapped){
        if(!silent){
          BOOST_LOG(rdWarningLog)<<"product "<<molIdx<<" has no mapped atoms.\n";
        }
        numWarnings++;
      }
      molIdx++;
    }
    if(!mapNumbersSeen.empty()){
      if(!silent){
        std::ostringstream ostr;
        ostr<<"mapped atoms in the reactants were not mapped in the products.\n";
        ostr<<"  unmapped numbers are: ";
        for(std::vector<int>::const_iterator ivIt=mapNumbersSeen.begin();
            ivIt!=mapNumbersSeen.end();++ivIt){
          ostr<< *ivIt << " ";
        }
        ostr<< "\n";
        BOOST_LOG(rdWarningLog)<<ostr.str();
      }
      numWarnings++;
    }
    
    return res;
  }

  bool isMoleculeReactantOfReaction(const ChemicalReaction &rxn,const ROMol &mol,
                                      unsigned int &which){
    if(!rxn.isInitialized()){
     throw ChemicalReactionException("initMatchers() must be called first");
    }
    which=0;
    for(MOL_SPTR_VECT::const_iterator iter=rxn.beginReactantTemplates();
        iter!=rxn.endReactantTemplates();++iter,++which){
      MatchVectType tvect;
      if(SubstructMatch(mol,**iter,tvect)){
        return true;
      }
    }
    return false;
  }
  bool isMoleculeReactantOfReaction(const ChemicalReaction &rxn,const ROMol &mol){
    unsigned int ignore;
    return isMoleculeReactantOfReaction(rxn,mol,ignore);
  }

  bool isMoleculeProductOfReaction(const ChemicalReaction &rxn,const ROMol &mol,
                                      unsigned int &which){
    if(!rxn.isInitialized()){
     throw ChemicalReactionException("initMatchers() must be called first");
    }
    which=0;
    for(MOL_SPTR_VECT::const_iterator iter=rxn.beginProductTemplates();
        iter!=rxn.endProductTemplates();++iter,++which){
      MatchVectType tvect;
      if(SubstructMatch(mol,**iter,tvect)){
        return true;
      }
    }
    return false;
  }
  bool isMoleculeProductOfReaction(const ChemicalReaction &rxn,const ROMol &mol){
    unsigned int ignore;
    return isMoleculeProductOfReaction(rxn,mol,ignore);
  }

  bool isMoleculeAgentOfReaction(const ChemicalReaction &rxn,const ROMol &mol,
		  unsigned int &which)
  {
    if(!rxn.isInitialized()){
	  throw ChemicalReactionException("initMatchers() must be called first");
	}
	which=0;
	for(MOL_SPTR_VECT::const_iterator iter=rxn.beginAgentTemplates();
	    iter!=rxn.endAgentTemplates();++iter,++which){
	  if(iter->get()->getNumHeavyAtoms() != mol.getNumHeavyAtoms()){
        continue;
	  }
      if(iter->get()->getNumBonds() != mol.getNumBonds()){
		continue;
      }
      // not possible, update property cache not possible for const molecules
//      if(iter->get()->getRingInfo()->numRings() != mol.getRingInfo()->numRings()){
//          return false;
//      }
      if(RDKit::Descriptors::calcAMW(*iter->get()) != RDKit::Descriptors::calcAMW(mol)){
		continue;
      }
      MatchVectType tvect;
      if(SubstructMatch(mol,**iter,tvect)){
        return true;
	  }
	}
	return false;
  }

  bool isMoleculeAgentOfReaction(const ChemicalReaction &rxn,const ROMol &mol){
	unsigned int ignore;
    return isMoleculeAgentOfReaction(rxn,mol,ignore);
  }

  void addRecursiveQueriesToReaction(ChemicalReaction &rxn,
                  const std::map<std::string,ROMOL_SPTR> &queries,
                  std::string propName,
                  std::vector<std::vector<std::pair<unsigned int,std::string> > > *reactantLabels) {
    if(!rxn.isInitialized()){
      throw ChemicalReactionException("initMatchers() must be called first");
    }

    if (reactantLabels!=NULL) {
        (*reactantLabels).resize(0);
    }

    for(MOL_SPTR_VECT::const_iterator rIt=rxn.beginReactantTemplates();
            rIt!=rxn.endReactantTemplates();++rIt){
        if (reactantLabels!=NULL) {
          std::vector<std::pair<unsigned int, std::string> > labels;
          addRecursiveQueries(**rIt, queries, propName, &labels);
          (*reactantLabels).push_back(labels);
        } else {
          addRecursiveQueries(**rIt, queries, propName);
        }
    }
  }

  namespace {
    // recursively looks for atomic number queries anywhere in this set of children
    // or its children
    int numComplexQueries(Queries::Query<int,Atom const *,true>::CHILD_VECT_CI childIt,
                          Queries::Query<int,Atom const *,true>::CHILD_VECT_CI endChildren){
      int res=0;
      while(childIt!=endChildren){
        std::string descr=(*childIt)->getDescription();
        if(descr=="AtomAtomicNum"||descr=="AtomNull"){
          ++res;
        } else {
          res += numComplexQueries((*childIt)->beginChildren(),
                                   (*childIt)->endChildren());
        }
        ++childIt;
      }
      return res;
    }
    // FIX: this is adapted from Fingerprints.cpp and we really should have code
    // like this centralized
    bool isComplexQuery(const Atom &a){
      if( !a.hasQuery()) return false;
      // negated things are always complex:
      if( a.getQuery()->getNegation()) return true;
      std::string descr=a.getQuery()->getDescription();
      if(descr=="AtomAtomicNum") return false;
      if(descr=="AtomOr" || descr=="AtomXor") return true;
      if(descr=="AtomAnd"){
        Queries::Query<int,Atom const *,true>::CHILD_VECT_CI childIt=a.getQuery()->beginChildren();
        int ncq=numComplexQueries(childIt,a.getQuery()->endChildren());
        if(ncq==1){
          return false;
        }
      }
      return true;
    }


    bool isChangedAtom(const Atom &rAtom,const Atom &pAtom,int mapNum,
                       const std::map<int,const Atom *> &mappedProductAtoms) {
      PRECONDITION(mappedProductAtoms.find(mapNum)!=mappedProductAtoms.end(),"atom not mapped in products");

      if(rAtom.getAtomicNum()!=pAtom.getAtomicNum() &&
         pAtom.getAtomicNum()>0 ){
        // the atomic number changed and the product wasn't a dummy
        return true;
      } else if(rAtom.getDegree() != pAtom.getDegree()){
        // the degree changed
        return true;
      } else if(pAtom.getAtomicNum()>0 && isComplexQuery(rAtom)){
        // more than a simple query
        return true;
      }

      // now check bond layout:
      std::map<unsigned int,const Bond *> reactantBonds;
      ROMol::ADJ_ITER nbrIdx,endNbrs;
      boost::tie(nbrIdx,endNbrs) = rAtom.getOwningMol().getAtomNeighbors(&rAtom);
      while(nbrIdx!=endNbrs){
        const ATOM_SPTR nbr=rAtom.getOwningMol()[*nbrIdx];
	    int mapNum;
        if(nbr->getPropIfPresent(common_properties::molAtomMapNumber, mapNum)){
          reactantBonds[mapNum]=rAtom.getOwningMol().getBondBetweenAtoms(rAtom.getIdx(),
                                                                         nbr->getIdx());
        } else {
          // if we have an un-mapped neighbor, we are automatically a reacting atom:
          return true;
        }
        ++nbrIdx;
      }
      boost::tie(nbrIdx,endNbrs) = pAtom.getOwningMol().getAtomNeighbors(&pAtom);
      while(nbrIdx!=endNbrs){
        const ATOM_SPTR nbr=pAtom.getOwningMol()[*nbrIdx];
	    int mapNum;
        if(nbr->getPropIfPresent(common_properties::molAtomMapNumber, mapNum)){
          // if we don't have a bond to a similarly mapped atom in the reactant,
          // we're done:
          if(reactantBonds.find(mapNum)==reactantBonds.end()){
            return true;
          }
          const Bond *rBond=reactantBonds[mapNum];
          const Bond *pBond=pAtom.getOwningMol().getBondBetweenAtoms(pAtom.getIdx(),
                                                                     nbr->getIdx());

          // bond comparison logic:
          if(rBond->hasQuery()){
            if(!pBond->hasQuery()) {
              // reactant query, product not query: always a change
              return true;
            } else {
              if( pBond->getQuery()->getDescription()=="BondNull" ){
                // null queries are trump, they match everything
              } else if( rBond->getBondType()==Bond::SINGLE && pBond->getBondType()==Bond::SINGLE &&
                  rBond->getQuery()->getDescription()=="BondOr" &&
                  pBond->getQuery()->getDescription()=="BondOr" ) {
                // The SMARTS parser tags unspecified bonds as single, but then adds
                // a query so that they match single or double.
                // these cases match
              } else {
                if(  rBond->getBondType()==pBond->getBondType() &&
                     rBond->getQuery()->getDescription()=="BondOrder" &&
                     pBond->getQuery()->getDescription()=="BondOrder" &&
                     static_cast<BOND_EQUALS_QUERY *>(rBond->getQuery())->getVal()==
                     static_cast<BOND_EQUALS_QUERY *>(pBond->getQuery())->getVal()
                     ) {
                  // bond order queries with equal orders also match
                } else {
                  // anything else does not match
                  return true;
                }
              }
            }
          } else if(pBond->hasQuery()) {
            // reactant not query, product query
            // if product is anything other than the null query
            // it's a change:
            if(pBond->getQuery()->getDescription()!="BondNull"){
              return true;
            }
            
          } else {
            // neither has a query, just compare the types
            if(rBond->getBondType()!=pBond->getBondType()){
              return true;
            }
          }
        }
        ++nbrIdx;
      }

      // haven't found anything to say that we are changed, so we must
      // not be
      return false;
    }

    template <class T>
    bool getMappedAtoms(T &rIt,
                        std::map<int,const Atom *> &mappedAtoms){
      ROMol::ATOM_ITER_PAIR atItP = rIt->getVertices();
      while(atItP.first != atItP.second ){
        const Atom *oAtom=(*rIt)[*(atItP.first++)].get();
        // we only worry about mapped atoms:
	    int mapNum;
        if(oAtom->getPropIfPresent(common_properties::molAtomMapNumber, mapNum)){
          mappedAtoms[mapNum]=oAtom;
        } else {
          // unmapped atom, return it
          return false;
        }
      }
      return true;
    }
  } // end of anonymous namespace
  
  VECT_INT_VECT getReactingAtoms(const ChemicalReaction &rxn,bool mappedAtomsOnly){
    if(!rxn.isInitialized()){
     throw ChemicalReactionException("initMatchers() must be called first");
    }
    VECT_INT_VECT res;
    res.resize(rxn.getNumReactantTemplates());

    // find mapped atoms in the products :
    std::map<int,const Atom *> mappedProductAtoms;
    for(MOL_SPTR_VECT::const_iterator rIt=rxn.beginProductTemplates();
        rIt!=rxn.endProductTemplates();++rIt){
      getMappedAtoms(*rIt,mappedProductAtoms);
    }

    // now loop over mapped atoms in the reactants, keeping track of
    // which reactant they are associated with, and check for changes.
    VECT_INT_VECT::iterator resIt=res.begin();
    for(MOL_SPTR_VECT::const_iterator rIt=rxn.beginReactantTemplates();
        rIt!=rxn.endReactantTemplates();++rIt,++resIt){
      ROMol::ATOM_ITER_PAIR atItP = (*rIt)->getVertices();
      while(atItP.first != atItP.second ){
        const Atom *oAtom=(**rIt)[*(atItP.first++)].get();
        // unmapped atoms are definitely changing:
	    int mapNum;
        if(!oAtom->getPropIfPresent(common_properties::molAtomMapNumber, mapNum)){
          if(!mappedAtomsOnly){
            resIt->push_back(oAtom->getIdx());
          }
        } else {
          // but mapped ones require more careful consideration
          // if this is found in a reactant:
          if(mappedProductAtoms.find(mapNum)!=mappedProductAtoms.end()){
            if( isChangedAtom(*oAtom,*(mappedProductAtoms[mapNum]),
                              mapNum,mappedProductAtoms) ){
              resIt->push_back(oAtom->getIdx());
            }
          }
        }
      }
    }
    return res;
  }

  void ChemicalReaction::removeUnmappedReactantTemplates(
    double thresholdUnmappedAtoms,
    bool moveToAgentTemplates,
    MOL_SPTR_VECT *targetVector)
  {
    MOL_SPTR_VECT res_reactantTemplates;
	for(MOL_SPTR_VECT::iterator iter = beginReactantTemplates();
	    iter != endReactantTemplates(); ++iter){
      if(isReactionTemplateMoleculeAgent(*iter->get(), thresholdUnmappedAtoms)){
        if(moveToAgentTemplates){
          m_agentTemplates.push_back(*iter);
        }
    	if(targetVector){
          targetVector->push_back(*iter);
        }
      }
      else{
    	  res_reactantTemplates.push_back(*iter);
      }
    }
	m_reactantTemplates.clear();
    m_reactantTemplates.insert(m_reactantTemplates.begin(),
    		res_reactantTemplates.begin(), res_reactantTemplates.end());
    res_reactantTemplates.clear();
  }

  void ChemicalReaction::removeUnmappedProductTemplates(
    double thresholdUnmappedAtoms,
    bool moveToAgentTemplates,
    MOL_SPTR_VECT *targetVector)
  {
    MOL_SPTR_VECT res_productTemplates;
	for(MOL_SPTR_VECT::iterator iter = beginProductTemplates();
	    iter != endProductTemplates(); ++iter){
      if(isReactionTemplateMoleculeAgent(*iter->get(), thresholdUnmappedAtoms)){
        if(moveToAgentTemplates){
          m_agentTemplates.push_back(*iter);
        }
    	if(targetVector){
          targetVector->push_back(*iter);
        }
      }
      else{
        res_productTemplates.push_back(*iter);
      }
	}
	m_productTemplates.clear();
    m_productTemplates.insert(m_productTemplates.begin(),
    		res_productTemplates.begin(), res_productTemplates.end());
    res_productTemplates.clear();
  }

} // end of RDKit namespace