rdkit/Code/GraphMol/MolStandardize/Normalize.cpp

//
//  Copyright (C) 2018-2021 Susan H. Leung and other RDKit contributors
//
//   @@ All Rights Reserved @@
//  This file is part of the RDKit.
//  The contents are covered by the terms of the BSD license
//  which is included in the file license.txt, found at the root
//  of the RDKit source tree.
//
#include "Normalize.h"
#include <string>
#include <GraphMol/RDKitBase.h>
#include <GraphMol/ChemReactions/Reaction.h>
#include <GraphMol/ChemReactions/ReactionParser.h>
#include <GraphMol/SmilesParse/SmilesWrite.h>
#include <GraphMol/SanitException.h>
#include <GraphMol/ChemTransforms/ChemTransforms.h>
#include <RDGeneral/BoostStartInclude.h>
#include <boost/flyweight.hpp>
#include <boost/flyweight/key_value.hpp>
#include <boost/flyweight/no_tracking.hpp>
#include <RDGeneral/BoostEndInclude.h>

using namespace std;
using namespace RDKit;

namespace RDKit {
class RWMol;
class ROMol;

namespace MolStandardize {

typedef boost::flyweight<
    boost::flyweights::key_value<std::string, TransformCatalogParams>,
    boost::flyweights::no_tracking>
    param_filename_flyweight;

typedef boost::flyweight<boost::flyweights::key_value<
                             std::vector<std::pair<std::string, std::string>>,
                             TransformCatalogParams>,
                         boost::flyweights::no_tracking>
    param_data_flyweight;

// unsigned int MAX_RESTARTS = 200;

// constructor
Normalizer::Normalizer() {
  BOOST_LOG(rdInfoLog) << "Initializing Normalizer\n";
  const TransformCatalogParams *tparams = &(
      param_filename_flyweight(defaultCleanupParameters.normalizations).get());
  this->d_tcat = new TransformCatalog(tparams);
  this->MAX_RESTARTS = 200;

  this->d_tcat->getCatalogParams()->initializeTransforms();
}

// overloaded constructor
Normalizer::Normalizer(const std::string normalizeFile,
                       const unsigned int maxRestarts) {
  BOOST_LOG(rdInfoLog) << "Initializing Normalizer\n";
  const TransformCatalogParams *tparams =
      &(param_filename_flyweight(normalizeFile).get());
  this->d_tcat = new TransformCatalog(tparams);
  this->MAX_RESTARTS = maxRestarts;

  this->d_tcat->getCatalogParams()->initializeTransforms();
}

// overloaded constructor
Normalizer::Normalizer(std::istream &normalizeStream,
                       const unsigned int maxRestarts) {
  BOOST_LOG(rdInfoLog) << "Initializing Normalizer\n";
  TransformCatalogParams tparams(normalizeStream);
  this->d_tcat = new TransformCatalog(&tparams);
  this->MAX_RESTARTS = maxRestarts;

  this->d_tcat->getCatalogParams()->initializeTransforms();
}

// overloaded constructor
Normalizer::Normalizer(
    const std::vector<std::pair<std::string, std::string>> &normalizations,
    const unsigned int maxRestarts) {
  BOOST_LOG(rdInfoLog) << "Initializing Normalizer\n";
  const TransformCatalogParams *tparams =
      &(param_data_flyweight(normalizations).get());
  this->d_tcat = new TransformCatalog(tparams);
  this->MAX_RESTARTS = maxRestarts;

  this->d_tcat->getCatalogParams()->initializeTransforms();
}

// destructor
Normalizer::~Normalizer() { delete d_tcat; }

void Normalizer::normalizeInPlace(RWMol &mol) {
  BOOST_LOG(rdInfoLog) << "Running Normalizer\n";
  PRECONDITION(this->d_tcat, "");
  const TransformCatalogParams *tparams = this->d_tcat->getCatalogParams();
  PRECONDITION(tparams, "no transform parameters");

  if (!mol.getNumAtoms()) {
    return;
  }

  const std::vector<std::shared_ptr<ChemicalReaction>> &transforms =
      tparams->getTransformations();

  // make the transforms are compatible with the
  // restrictions on in-place reactions
  for (auto &transform : transforms) {
    if (transform->getNumProductTemplates() != 1 ||
        transform->getNumReactantTemplates() != 1 ||
        transform->getProducts()[0]->getNumAtoms() >
            transform->getReactants()[0]->getNumAtoms()) {
      throw ValueErrorException(
          "normalizeInPlace can only be used with transforms which have a single reactant and single product. The number of atoms in the product cannot be larger than the number of atoms in the reactant.");
    }
  }
  // we might want ring info
  if (!mol.getRingInfo()->isSymmSssr()) {
    MolOps::symmetrizeSSSR(mol);
  }
  for (unsigned int i = 0; i < MAX_RESTARTS; ++i) {
    bool loop_break = false;
    // Iterate through Normalization transforms and apply each in order
    for (auto &transform : transforms) {
      constexpr bool removeUnmatchedAtoms = false;
      if (transform->runReactant(mol, removeUnmatchedAtoms)) {
        BOOST_LOG(rdInfoLog)
            << "Rule applied: "
            << transform->getProp<std::string>(common_properties::_Name)
            << "\n";
        constexpr unsigned int sanitizeOps = MolOps::SANITIZE_ALL ^
                                             MolOps::SANITIZE_CLEANUP ^
                                             MolOps::SANITIZE_PROPERTIES;
        unsigned int failed;
        try {
          MolOps::sanitizeMol(mol, failed, sanitizeOps);
        } catch (MolSanitizeException &) {
          BOOST_LOG(rdInfoLog) << "FAILED sanitizeMol.\n";
        }
        loop_break = true;
        break;
      }
    }
    // For loop finishes normally, all applicable transforms have been applied
    if (!loop_break) {
      return;
    }
  }
  BOOST_LOG(rdInfoLog) << "Gave up normalization after " << MAX_RESTARTS
                       << " restarts.\n";
}

ROMol *Normalizer::normalize(const ROMol &mol) {
  BOOST_LOG(rdInfoLog) << "Running Normalizer\n";
  PRECONDITION(this->d_tcat, "");
  const TransformCatalogParams *tparams = this->d_tcat->getCatalogParams();

  PRECONDITION(tparams, "");
  if (!mol.getNumAtoms()) {
    return new ROMol(mol);
  }
  const std::vector<std::shared_ptr<ChemicalReaction>> &transforms =
      tparams->getTransformations();
  bool sanitizeFrags = false;
  MOL_SPTR_VECT frags = MolOps::getMolFrags(mol, sanitizeFrags);
  MOL_SPTR_VECT nfrags;  //( frags.size() );
  for (const auto &frag : frags) {
    frag->updatePropertyCache(false);
    ROMOL_SPTR nfrag(this->normalizeFragment(*frag, transforms));
    nfrags.push_back(nfrag);
  }
  auto *outmol = new ROMol(*(nfrags.back()));
  nfrags.pop_back();
  for (const auto &nfrag : nfrags) {
    ROMol *tmol = combineMols(*outmol, *nfrag);
    delete outmol;
    outmol = tmol;
    //		delete nfrag;
  }
  return outmol;
}

ROMOL_SPTR Normalizer::normalizeFragment(
    const ROMol &mol,
    const std::vector<std::shared_ptr<ChemicalReaction>> &transforms) const {
  ROMOL_SPTR nfrag(new ROMol(mol));
  if (!nfrag->getRingInfo()->isFindFastOrBetter()) {
    MolOps::fastFindRings(*nfrag);
  }
  std::set<std::string> seenProductSmiles;
  for (unsigned int i = 0; i < MAX_RESTARTS; ++i) {
    bool loop_break = false;
    // Iterate through Normalization transforms and apply each in order
    for (auto &transform : transforms) {
      SmilesMolPair product = applyTransform(nfrag, *transform);
      if (!product.first.empty() && !seenProductSmiles.count(product.first)) {
        seenProductSmiles.insert(product.first);
        BOOST_LOG(rdInfoLog)
            << "Rule applied: "
            << transform->getProp<std::string>(common_properties::_Name)
            << "\n";
        nfrag = product.second;
        loop_break = true;
        break;
      }
    }
    // For loop finishes normally, all applicable transforms have been applied
    if (!loop_break) {
      return nfrag;
    }
  }
  BOOST_LOG(rdInfoLog) << "Gave up normalization after " << MAX_RESTARTS
                       << " restarts.\n";
  return nfrag;
}

SmilesMolPair Normalizer::applyTransform(const ROMOL_SPTR &mol,
                                         ChemicalReaction &transform) const {
  // Repeatedly apply normalization transform to molecule until no changes
  // occur.
  //
  // It is possible for multiple products to be produced when a rule is applied.
  // The rule is applied repeatedly to each of the products, until no further
  // changes occur or after 20 attempts.
  //
  // If there are multiple unique products after the final application, the
  // first product (sorted alphabetically by SMILES) is chosen.

  SmilesMolPair smilesMolPair{std::string(), mol};

  // REVIEW: what's the source of the 20 in the next line?
  for (unsigned int i = 0; i < 20; ++i) {
    std::map<std::string, ROMOL_SPTR> pdts;
    std::vector<MOL_SPTR_VECT> products =
        transform.runReactants({smilesMolPair.second});
    for (auto &pdt : products) {
      // shared_ptr<ROMol> p0( new RWMol(*pdt[0]) );
      //				std::cout << MolToSmiles(*p0) <<
      // std::endl;
      unsigned int failed;
      try {
        auto *tmol = static_cast<RWMol *>(pdt.front().get());
        // we'll allow atoms with a valence that's too high to make it
        // through, but we should fail if we just created something that
        // can't, for example, be kekulized.
        unsigned int sanitizeOps = MolOps::SANITIZE_ALL ^
                                   MolOps::SANITIZE_CLEANUP ^
                                   MolOps::SANITIZE_PROPERTIES;
        MolOps::sanitizeMol(*tmol, failed, sanitizeOps);
        pdts[MolToSmiles(*tmol)] = pdt.front();
      } catch (MolSanitizeException &) {
        BOOST_LOG(rdInfoLog) << "FAILED sanitizeMol.\n";
      }
    }
    if (!pdts.empty()) {
      smilesMolPair = std::move(*pdts.begin());
    } else {
      if (i) {
        return smilesMolPair;
      }
      return std::make_pair(std::string(), nullptr);
    }
  }
  return smilesMolPair;
}

}  // namespace MolStandardize
}  // namespace RDKit