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//
// Copyright (C) 2025 David Cosgrove 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 <cmath>
#include <limits>
#include <boost/numeric/conversion/cast.hpp>
#include <RDGeneral/export.h>
#include <GraphMol/MolOps.h>
#include <GraphMol/DistGeomHelpers/Embedder.h>
#include <GraphMol/EnumerateStereoisomers/EnumerateStereoisomers.h>
#include <GraphMol/EnumerateStereoisomers/Flippers.h>
#include <GraphMol/SmilesParse/SmilesWrite.h>
namespace RDKit {
namespace EnumerateStereoisomers {
StereoisomerEnumerator::StereoisomerEnumerator(
const ROMol &mol, const StereoEnumerationOptions &options, bool verbose)
: d_mol(mol), d_options(options), d_verbose(verbose) {
if (d_mol.getNumConformers()) {
Chirality::wedgeMolBonds(d_mol, &d_mol.getConformer());
}
buildFlippers();
// Clear unhelpful stuff out
for (auto atom : d_mol.atoms()) {
atom->clearProp("_CIPCode");
}
for (auto bond : d_mol.bonds()) {
if (bond->getBondDir() == Bond::BondDir::EITHERDOUBLE ||
bond->getBondDir() == Bond::BondDir::UNKNOWN) {
bond->setBondDir(Bond::BondDir::NONE);
}
}
if (d_flippers.empty()) {
d_totalPoss = 1;
} else {
d_mol.setProp<std::string>("_MolFileChiralFlag", "1");
try {
d_totalPoss = boost::numeric_cast<unsigned long>(std::pow(
std::uint64_t(2), static_cast<std::uint64_t>(d_flippers.size())));
} catch (boost::numeric::positive_overflow &e) {
d_totalPoss = std::numeric_limits<std::uint64_t>::max();
}
}
if (d_options.maxIsomers) {
d_numToReturn = std::min(getStereoisomerCount(), d_options.maxIsomers);
} else {
d_numToReturn = getStereoisomerCount();
}
if (d_options.randomSeed == -1) {
d_randGen.reset(new std::mt19937(std::random_device()()));
} else {
d_randGen.reset(new std::mt19937(d_options.randomSeed));
}
}
std::uint64_t StereoisomerEnumerator::getStereoisomerCount() const {
return d_totalPoss;
}
std::unique_ptr<ROMol> StereoisomerEnumerator::next() {
if (d_numReturned == d_numToReturn) {
return std::unique_ptr<ROMol>();
}
auto isomer = generateRandomIsomer();
++d_numReturned;
return isomer;
}
void StereoisomerEnumerator::buildFlippers() {
auto sis = Chirality::findPotentialStereo(d_mol, true, true);
for (const auto &si : sis) {
if (d_options.onlyUnassigned &&
si.specified != Chirality::StereoSpecified::Unknown &&
si.specified != Chirality::StereoSpecified::Unspecified) {
continue;
}
if (si.type == Chirality::StereoType::Atom_Tetrahedral) {
d_flippers.push_back(std::unique_ptr<details::Flipper>(
new details::AtomFlipper(d_mol, si)));
} else if (si.type == Chirality::StereoType::Bond_Double) {
std::unique_ptr<details::BondFlipper> newFlipper(
new details::BondFlipper(d_mol, si));
if (newFlipper->dp_bond) {
d_flippers.push_back(std::move(newFlipper));
}
} else if (si.type == Chirality::StereoType::Bond_Atropisomer) {
std::unique_ptr<details::AtropisomerFlipper> newFlipper(
new details::AtropisomerFlipper(d_mol, si));
d_flippers.push_back(std::move(newFlipper));
}
}
if (d_options.onlyUnassigned) {
// otherwise these will be counted twice
for (const auto &group : d_mol.getStereoGroups()) {
if (group.getGroupType() != StereoGroupType::STEREO_ABSOLUTE) {
d_flippers.push_back(std::unique_ptr<details::Flipper>(
new details::StereoGroupFlipper(group)));
}
}
}
}
std::unique_ptr<ROMol> StereoisomerEnumerator::generateRandomIsomer() {
boost::dynamic_bitset<> nextConfig{d_flippers.size()};
while (d_seen.size() < d_totalPoss) {
for (size_t i = 0; i < d_flippers.size(); i++) {
bool config = d_randDis(*d_randGen);
nextConfig[i] = config;
}
if (d_seen.find(nextConfig) == d_seen.end()) {
d_seen.insert(nextConfig);
for (size_t i = 0; i < d_flippers.size(); i++) {
d_flippers[i]->flip(nextConfig[i]);
}
// We don't need StereoGroups any more so remove them.
std::unique_ptr<ROMol> isomer;
if (!d_mol.getStereoGroups().empty()) {
isomer.reset(new RWMol(d_mol));
isomer->setStereoGroups(std::vector<StereoGroup>());
} else {
isomer.reset(new ROMol(d_mol));
}
MolOps::setDoubleBondNeighborDirections(*isomer);
isomer->clearComputedProps(false);
MolOps::assignStereochemistry(*isomer, true, true, true);
if (d_options.unique) {
auto smi =
MolToCXSmiles(*isomer, SmilesWriteParams(),
SmilesWrite::CXSmilesFields::CX_ALL_BUT_COORDS);
if (d_generatedIsomers.find(smi) != d_generatedIsomers.end()) {
continue;
}
d_generatedIsomers.insert(smi);
}
if (d_options.tryEmbedding) {
if (embeddable(*isomer)) {
return isomer;
}
if (d_verbose) {
BOOST_LOG(rdInfoLog)
<< MolToSmiles(*isomer) << " failed to embed." << std::endl;
}
} else {
return isomer;
}
}
}
return std::unique_ptr<ROMol>();
}
bool StereoisomerEnumerator::embeddable(ROMol &isomer) {
std::unique_ptr<ROMol> isomerWithHs(MolOps::addHs(isomer));
auto cid = DGeomHelpers::EmbedMolecule(*isomerWithHs);
if (cid >= 0) {
Conformer *conf = new Conformer(isomer.getNumAtoms());
for (unsigned int i = 0; i < isomer.getNumAtoms(); i++) {
conf->setAtomPos(i, isomerWithHs->getConformer().getAtomPos(i));
}
isomer.addConformer(conf);
}
return cid >= 0;
}
} // namespace EnumerateStereoisomers
} // namespace RDKit
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