static inline void processCuts(
size_t i, size_t maxCuts, BondVector_t& bonds_selected,
const std::vector<BondVector_t>& matching_bonds, const ROMol& mol,
std::vector<std::pair<ROMOL_SPTR, ROMOL_SPTR> >& res) {
for (size_t x = i; x < matching_bonds.size(); x++) {
appendBonds(bonds_selected, matching_bonds[x]);
addResult(res, mol, bonds_selected, maxCuts);
if (bonds_selected.size() < maxCuts)
processCuts(x + 1, maxCuts, bonds_selected, matching_bonds, mol, res);
bonds_selected.pop_back();
}
}
bool fragmentMol(const ROMol& mol,
std::vector<std::pair<ROMOL_SPTR, ROMOL_SPTR> >& res,
const std::vector<unsigned int>& bondsToCut,
unsigned int minCuts,
unsigned int maxCuts) {
std::vector<BondVector_t> matching_bonds; // List of matched query's bonds
BOOST_FOREACH(unsigned int i, bondsToCut) {
const Bond *bond = mol.getBondWithIdx(i);
BondVector_t bonds;
unsigned int a1 = bond->getBeginAtomIdx();
unsigned int a2 = bond->getEndAtomIdx();
bonds.push_back( std::make_pair(a1, a2) );
matching_bonds.push_back(bonds);
}
// loop to generate every cut in the molecule
BondVector_t bonds_selected;
processCuts(0, minCuts, maxCuts, bonds_selected, matching_bonds, mol, res);
return true;
}
static inline void processCuts(
size_t i, size_t minCuts, size_t maxCuts, BondVector_t& bonds_selected,
const std::vector<BondVector_t>& matching_bonds, const ROMol& mol,
std::vector<std::pair<ROMOL_SPTR, ROMOL_SPTR> >& res) {
if(maxCuts < minCuts)
throw ValueErrorException("supplied maxCuts is less than minCuts");
if(minCuts==0)
throw ValueErrorException("minCuts must be greater than 0");
for (size_t x = i; x < matching_bonds.size(); x++) {
appendBonds(bonds_selected, matching_bonds[x]);
if(bonds_selected.size() >= minCuts) {
addResult(res, mol, bonds_selected, maxCuts);
}
if (bonds_selected.size() < maxCuts) {
processCuts(x + 1, minCuts, maxCuts, bonds_selected, matching_bonds, mol, res);
}
bonds_selected.pop_back();
}
}
static void addResult(std::vector<std::pair<ROMOL_SPTR, ROMOL_SPTR> >&
res, // const SignatureVector& resSignature,
const ROMol& mol,
const BondVector_t& bonds_selected, size_t maxCuts) {
#ifdef _DEBUG
std::cout << res.size() + 1 << ": ";
#endif
RWMol em(mol);
// loop through the bonds to delete. == deleteBonds()
unsigned isotope = 0;
std::map<unsigned, unsigned> isotope_track;
for (size_t i = 0; i < bonds_selected.size(); i++) {
#ifdef _DEBUG
{
std::string symbol =
em.getAtomWithIdx(bonds_selected[i].first)->getSymbol();
int label = 0;
em.getAtomWithIdx(bonds_selected[i].first)
->getPropIfPresent(common_properties::molAtomMapNumber, label);
char a1[32];
if (0 == label)
sprintf(a1, "\'%s\'", symbol.c_str(), label);
else
sprintf(a1, "\'%s:%u\'", symbol.c_str(), label);
symbol = em.getAtomWithIdx(bonds_selected[i].second)->getSymbol();
label = 0;
em.getAtomWithIdx(bonds_selected[i].second)
->getPropIfPresent(common_properties::molAtomMapNumber, label);
char a2[32];
if (0 == label)
sprintf(a2, "\'%s\'", symbol.c_str(), label);
else
sprintf(a2, "\'%s:%u\'", symbol.c_str(), label);
std::cout << "(" << bonds_selected[i].first << a1 << ","
<< bonds_selected[i].second << a2 << ") ";
}
#endif
isotope += 1;
// remove the bond
em.removeBond(bonds_selected[i].first, bonds_selected[i].second);
// now add attachement points and set attachment point lables
Atom* a = new Atom(0);
a->setProp(common_properties::molAtomMapNumber, (int)isotope);
unsigned newAtomA = em.addAtom(a, true, true);
em.addBond(bonds_selected[i].first, newAtomA, Bond::SINGLE);
a = new Atom(0);
a->setProp(common_properties::molAtomMapNumber, (int)isotope);
unsigned newAtomB = em.addAtom(a, true, true);
em.addBond(bonds_selected[i].second, newAtomB, Bond::SINGLE);
// keep track of where to put isotopes
isotope_track[newAtomA] = isotope;
isotope_track[newAtomB] = isotope;
}
#ifdef _DEBUG
std::cout << "\n";
#endif
RWMOL_SPTR core, side_chains; // core & side_chains output molecules
if (isotope == 1) {
side_chains = RWMOL_SPTR(new RWMol(em)); // output = '%s,%s,,%s.%s'
// DEBUG PRINT
#ifdef _DEBUG
// OK: std::cout<<res.size()+1<<" isotope="<< isotope <<","<<
// MolToSmiles(*side_chains, true) <<"\n";
#endif
} else if (isotope >= 2) {
std::vector<std::vector<int> > frags;
unsigned int nFrags = MolOps::getMolFrags(em, frags);
//#check if its a valid triple or bigger cut. matchObj = re.search(
//'\*.*\*.*\*', f)
// check if exists a fragment with maxCut connection points (*.. *.. *)
if (isotope >= 3) {
bool valid = false;
for (size_t i = 0; i < nFrags; i++) {
unsigned nLabels = 0;
for (size_t ai = 0; ai < frags[i].size(); ai++) {
if (isotope_track.end() !=
isotope_track.find(frags[i][ai])) // new added atom
++nLabels; // found connection point
}
if (nLabels >=
maxCuts) { // looks like it should be selected as core ! ??????
valid = true;
break;
}
}
if (!valid) {
#ifdef _DEBUG
std::cout << "isotope>=3: invalid fragments. fragment with maxCut "
"connection points not found"
<< "\n";
#endif
return;
}
}
size_t iCore = std::numeric_limits<size_t>::max();
side_chains = RWMOL_SPTR(new RWMol);
std::map<unsigned, unsigned>
visitedBonds; // key is bond index in source molecule
unsigned maxAttachments = 0;
for (size_t i = 0; i < frags.size(); i++) {
unsigned nAttachments = 0;
for (size_t ai = 0; ai < frags[i].size(); ai++) {
if (isotope_track.end() !=
isotope_track.find(
frags[i][ai])) // == if(a->hasProp("molAtomMapNumber"))
++nAttachments;
}
if (maxAttachments < nAttachments) maxAttachments = nAttachments;
if (1 == nAttachments) { // build side-chain set of molecules from
// selected fragment
std::map<unsigned, unsigned>
newAtomMap; // key is atom index in source molecule
for (size_t ai = 0; ai < frags[i].size(); ai++) {
Atom* a = em.getAtomWithIdx(frags[i][ai]);
newAtomMap[frags[i][ai]] =
side_chains->addAtom(a->copy(), true, true);
}
// add all bonds from this fragment
for (size_t ai = 0; ai < frags[i].size(); ai++) {
Atom* a = em.getAtomWithIdx(frags[i][ai]);
ROMol::OEDGE_ITER beg, end;
for (boost::tie(beg, end) = em.getAtomBonds(a); beg != end; ++beg) {
const BOND_SPTR bond = em[*beg];
if (newAtomMap.end() == newAtomMap.find(bond->getBeginAtomIdx()) ||
newAtomMap.end() == newAtomMap.find(bond->getEndAtomIdx()) ||
visitedBonds.end() != visitedBonds.find(bond->getIdx()))
continue;
unsigned ai1 = newAtomMap[bond->getBeginAtomIdx()];
unsigned ai2 = newAtomMap[bond->getEndAtomIdx()];
unsigned bi = side_chains->addBond(ai1, ai2, bond->getBondType());
visitedBonds[bond->getIdx()] = bi;
}
}
} else { // select the core fragment
// DEBUG PRINT
#ifdef _DEBUG
if (iCore != -1)
std::cout << "Next CORE found. iCore=" << iCore << " New i=" << i
<< " nAttachments=" << nAttachments << "\n";
#endif
if (nAttachments >= maxAttachments) // Choose a fragment with maximal
// number of connection points as a
// core
iCore = i;
}
}
// build core molecule from selected fragment
if (iCore != std::numeric_limits<size_t>::max()) {
core = RWMOL_SPTR(new RWMol);
visitedBonds.clear();
std::map<unsigned, unsigned>
newAtomMap; // key is atom index in source molecule
for (size_t i = 0; i < frags[iCore].size(); i++) {
unsigned ai = frags[iCore][i];
Atom* a = em.getAtomWithIdx(ai);
newAtomMap[ai] = core->addAtom(a->copy(), true, true);
}
// add all bonds from this fragment
for (size_t ai = 0; ai < frags[iCore].size(); ai++) {
Atom* a = em.getAtomWithIdx(frags[iCore][ai]);
ROMol::OEDGE_ITER beg, end;
for (boost::tie(beg, end) = em.getAtomBonds(a); beg != end; ++beg) {
const BOND_SPTR bond = em[*beg];
if (newAtomMap.end() == newAtomMap.find(bond->getBeginAtomIdx()) ||
newAtomMap.end() == newAtomMap.find(bond->getEndAtomIdx()) ||
visitedBonds.end() != visitedBonds.find(bond->getIdx()))
continue;
unsigned ai1 = newAtomMap[bond->getBeginAtomIdx()];
unsigned ai2 = newAtomMap[bond->getEndAtomIdx()];
unsigned bi = core->addBond(ai1, ai2, bond->getBondType());
visitedBonds[bond->getIdx()] = bi;
}
}
// DEBUG PRINT
#ifdef _DEBUG
// std::cout<<res.size()+1<<" isotope="<< isotope <<" "<< MolToSmiles(*core,
// true)<<", "<<MolToSmiles(*side_chains, true)<<"\n";
#endif
} // iCore != -1
}
// check for duplicates:
bool resFound = false;
size_t ri = 0;
for (ri = 0; ri < res.size(); ri++) {
const std::pair<ROMOL_SPTR, ROMOL_SPTR>& r = res[ri];
if (side_chains->getNumAtoms() == r.second->getNumAtoms() &&
side_chains->getNumBonds() == r.second->getNumBonds() &&
((NULL == core.get() && NULL == r.first.get()) ||
(NULL != core.get() && NULL != r.first.get() &&
core->getNumAtoms() == r.first->getNumAtoms() &&
core->getNumBonds() == r.first->getNumBonds()))) {
// ToDo accurate check:
// 1. compare hash code
if (computeMorganCodeHash(*side_chains) ==
computeMorganCodeHash(*r.second) &&
(NULL == core ||
computeMorganCodeHash(*core) == computeMorganCodeHash(*r.first))) {
// 2. final check to exclude hash collisions
// We decided that it does not neccessary to implement
resFound = true;
break;
}
}
}
if (!resFound) {
//std::cerr << "**********************" << std::endl;
// From rfrag.py
// now change the labels on sidechains and core
// to get the new labels, cansmi the dot-disconnected side chains
// the first fragment in the side chains has attachment label 1, 2nd: 2, 3rd: 3
// then change the labels accordingly in the core
std::map<unsigned int, int> canonicalAtomMaps;
if( side_chains.get() ) {
RWMol tmp_side_chain(*(side_chains.get()));
std::vector<int> oldMaps(tmp_side_chain.getNumAtoms(), 0);
// clear atom labels (they are used in canonicalization)
// and move them to dummy storage
for (ROMol::AtomIterator at = tmp_side_chain.beginAtoms(); at != tmp_side_chain.endAtoms();
++at) {
int label = 0;
if ((*at)->getPropIfPresent(common_properties::molAtomMapNumber, label) ) {
(*at)->clearProp(common_properties::molAtomMapNumber);
oldMaps[(*at)->getIdx()] = label;
}
}
const bool doIsomericSmiles = true; // should this be false???
std::string smiles = MolToSmiles(tmp_side_chain, doIsomericSmiles);
//std::cerr << "smiles: " << smiles << std::endl;
// Get the canonical output order and use it to remap
// the atom maps int the side chains
// these will get reapplied to the core (if there is a core)
const std::vector<unsigned int> &ranks = tmp_side_chain.getProp<
std::vector<unsigned int> >(
common_properties::_smilesAtomOutputOrder);
std::vector<std::pair<unsigned int, int> > rankedAtoms;
for(size_t idx=0;idx<ranks.size();++idx) {
unsigned int atom_idx = ranks[idx];
if(oldMaps[atom_idx] >0) {
const int label = oldMaps[atom_idx];
//std::cerr << "atom_idx: " << atom_idx << " rank: " << ranks[atom_idx] <<
// " molAtomMapNumber: " << label << std::endl;
rankedAtoms.push_back(std::make_pair(idx, label));
}
}
std::sort(rankedAtoms.begin(), rankedAtoms.end());
int nextMap = 0;
for(size_t i=0;i<rankedAtoms.size();++i) {
if(canonicalAtomMaps.find(rankedAtoms[i].second) == canonicalAtomMaps.end()) {
//std::cerr << "Remapping: " << rankedAtoms[i].second << " " << " to " << (i+1) <<
// std::endl;
canonicalAtomMaps[rankedAtoms[i].second] = ++nextMap;
}
}
}
//std::cerr << "======== Remap core " << std::endl;
if( core.get() ) { // remap core if it exists
for (ROMol::AtomIterator at = core->beginAtoms(); at != core->endAtoms();
++at) {
int label = 0;
if ((*at)->getPropIfPresent(common_properties::molAtomMapNumber, label) ) {
//std::cerr << "remapping core: " << label << " :" << canonicalAtomMaps[label] <<
// std::endl;
(*at)->setProp(common_properties::molAtomMapNumber, canonicalAtomMaps[label]);
}
}
}
//std::cerr << "======== Remap side-chain " << std::endl;
for (ROMol::AtomIterator at = side_chains->beginAtoms(); at != side_chains->endAtoms();
++at) {
int label = 0;
if ((*at)->getPropIfPresent(common_properties::molAtomMapNumber, label) ) {
//std::cerr << "remapping side chain: " << label << " :" <<
// canonicalAtomMaps[label] << std::endl;
(*at)->setProp(common_properties::molAtomMapNumber, canonicalAtomMaps[label]);
}
}
res.push_back(std::pair<ROMOL_SPTR, ROMOL_SPTR>(core, side_chains)); //
}
#ifdef _DEBUG
else
std::cout << res.size() + 1 << " --- DUPLICATE Result FOUND --- ri=" << ri
<< "\n";
#endif
}
//=====================================================================
static inline void appendBonds(BondVector_t& bonds,
const BondVector_t& matching_bonds) {
for (BondVector_t::const_iterator b = matching_bonds.begin();
b != matching_bonds.end(); ++b)
bonds.push_back(*b);
}
static void addResult(std::vector<std::pair<ROMOL_SPTR, ROMOL_SPTR> >&
res, // const SignatureVector& resSignature,
const ROMol& mol,
const BondVector_t& bonds_selected, size_t maxCuts) {
#ifdef _DEBUG
std::cout << res.size() + 1 << ": ";
#endif
RWMol em(mol);
// loop through the bonds to delete. == deleteBonds()
unsigned isotope = 0;
std::map<unsigned, unsigned> isotope_track;
for (size_t i = 0; i < bonds_selected.size(); i++) {
#ifdef _DEBUG
{
std::string symbol =
em.getAtomWithIdx(bonds_selected[i].first)->getSymbol();
int label = 0;
em.getAtomWithIdx(bonds_selected[i].first)
->getPropIfPresent(common_properties::molAtomMapNumber, label);
char a1[32];
if (0 == label)
sprintf(a1, "\'%s\'", symbol.c_str(), label);
else
sprintf(a1, "\'%s:%u\'", symbol.c_str(), label);
symbol = em.getAtomWithIdx(bonds_selected[i].second)->getSymbol();
label = 0;
em.getAtomWithIdx(bonds_selected[i].second)
->getPropIfPresent(common_properties::molAtomMapNumber, label);
char a2[32];
if (0 == label)
sprintf(a2, "\'%s\'", symbol.c_str(), label);
else
sprintf(a2, "\'%s:%u\'", symbol.c_str(), label);
std::cout << "(" << bonds_selected[i].first << a1 << ","
<< bonds_selected[i].second << a2 << ") ";
}
#endif
isotope += 1;
// remove the bond
em.removeBond(bonds_selected[i].first, bonds_selected[i].second);
// now add attachement points and set attachment point lables
Atom* a = new Atom(0);
a->setProp(common_properties::molAtomMapNumber, (int)isotope);
unsigned newAtomA = em.addAtom(a, true, true);
em.addBond(bonds_selected[i].first, newAtomA, Bond::SINGLE);
a = new Atom(0);
a->setProp(common_properties::molAtomMapNumber, (int)isotope);
unsigned newAtomB = em.addAtom(a, true, true);
em.addBond(bonds_selected[i].second, newAtomB, Bond::SINGLE);
// keep track of where to put isotopes
isotope_track[newAtomA] = isotope;
isotope_track[newAtomB] = isotope;
}
#ifdef _DEBUG
std::cout << "\n";
#endif
RWMOL_SPTR core, side_chains; // core & side_chains output molecules
if (isotope == 1) {
side_chains = RWMOL_SPTR(new RWMol(em)); // output = '%s,%s,,%s.%s'
// DEBUG PRINT
#ifdef _DEBUG
// OK: std::cout<<res.size()+1<<" isotope="<< isotope <<","<<
// MolToSmiles(*side_chains, true) <<"\n";
#endif
} else if (isotope >= 2) {
std::vector<std::vector<int> > frags;
unsigned int nFrags = MolOps::getMolFrags(em, frags);
//#check if its a valid triple or bigger cut. matchObj = re.search(
//'\*.*\*.*\*', f)
// check if exists a fragment with maxCut connection points (*.. *.. *)
if (isotope >= 3) {
bool valid = false;
for (size_t i = 0; i < nFrags; i++) {
unsigned nLabels = 0;
for (size_t ai = 0; ai < frags[i].size(); ai++) {
if (isotope_track.end() !=
isotope_track.find(frags[i][ai])) // new added atom
++nLabels; // found connection point
}
if (nLabels >=
maxCuts) { // looks like it should be selected as core ! ??????
valid = true;
break;
}
}
if (!valid) {
#ifdef _DEBUG
std::cout << "isotope>=3: invalid fragments. fragment with maxCut "
"connection points not found"
<< "\n";
#endif
return;
}
}
size_t iCore = std::numeric_limits<size_t>::max();
side_chains = RWMOL_SPTR(new RWMol);
std::map<unsigned, unsigned>
visitedBonds; // key is bond index in source molecule
unsigned maxAttachments = 0;
for (size_t i = 0; i < frags.size(); i++) {
unsigned nAttachments = 0;
for (size_t ai = 0; ai < frags[i].size(); ai++) {
if (isotope_track.end() !=
isotope_track.find(
frags[i][ai])) // == if(a->hasProp("molAtomMapNumber"))
++nAttachments;
}
if (maxAttachments < nAttachments) maxAttachments = nAttachments;
if (1 == nAttachments) { // build side-chain set of molecules from
// selected fragment
std::map<unsigned, unsigned>
newAtomMap; // key is atom index in source molecule
for (size_t ai = 0; ai < frags[i].size(); ai++) {
Atom* a = em.getAtomWithIdx(frags[i][ai]);
newAtomMap[frags[i][ai]] =
side_chains->addAtom(a->copy(), true, true);
}
// add all bonds from this fragment
for (size_t ai = 0; ai < frags[i].size(); ai++) {
Atom* a = em.getAtomWithIdx(frags[i][ai]);
ROMol::OEDGE_ITER beg, end;
for (boost::tie(beg, end) = em.getAtomBonds(a); beg != end; ++beg) {
const BOND_SPTR bond = em[*beg];
if (newAtomMap.end() == newAtomMap.find(bond->getBeginAtomIdx()) ||
newAtomMap.end() == newAtomMap.find(bond->getEndAtomIdx()) ||
visitedBonds.end() != visitedBonds.find(bond->getIdx()))
continue;
unsigned ai1 = newAtomMap[bond->getBeginAtomIdx()];
unsigned ai2 = newAtomMap[bond->getEndAtomIdx()];
unsigned bi = side_chains->addBond(ai1, ai2, bond->getBondType());
visitedBonds[bond->getIdx()] = bi;
}
}
} else { // select the core fragment
// DEBUG PRINT
#ifdef _DEBUG
if (iCore != -1)
std::cout << "Next CORE found. iCore=" << iCore << " New i=" << i
<< " nAttachments=" << nAttachments << "\n";
#endif
if (nAttachments >= maxAttachments) // Choose a fragment with maximal
// number of connection points as a
// core
iCore = i;
}
}
// build core molecule from selected fragment
if (iCore != std::numeric_limits<size_t>::max()) {
core = RWMOL_SPTR(new RWMol);
visitedBonds.clear();
std::map<unsigned, unsigned>
newAtomMap; // key is atom index in source molecule
for (size_t i = 0; i < frags[iCore].size(); i++) {
unsigned ai = frags[iCore][i];
Atom* a = em.getAtomWithIdx(ai);
newAtomMap[ai] = core->addAtom(a->copy(), true, true);
}
// add all bonds from this fragment
for (size_t ai = 0; ai < frags[iCore].size(); ai++) {
Atom* a = em.getAtomWithIdx(frags[iCore][ai]);
ROMol::OEDGE_ITER beg, end;
for (boost::tie(beg, end) = em.getAtomBonds(a); beg != end; ++beg) {
const BOND_SPTR bond = em[*beg];
if (newAtomMap.end() == newAtomMap.find(bond->getBeginAtomIdx()) ||
newAtomMap.end() == newAtomMap.find(bond->getEndAtomIdx()) ||
visitedBonds.end() != visitedBonds.find(bond->getIdx()))
continue;
unsigned ai1 = newAtomMap[bond->getBeginAtomIdx()];
unsigned ai2 = newAtomMap[bond->getEndAtomIdx()];
unsigned bi = core->addBond(ai1, ai2, bond->getBondType());
visitedBonds[bond->getIdx()] = bi;
}
}
// DEBUG PRINT
#ifdef _DEBUG
// std::cout<<res.size()+1<<" isotope="<< isotope <<" "<< MolToSmiles(*core,
// true)<<", "<<MolToSmiles(*side_chains, true)<<"\n";
#endif
} // iCore != -1
}
// check for dublicates:
bool resFound = false;
size_t ri = 0;
for (ri = 0; ri < res.size(); ri++) {
const std::pair<ROMOL_SPTR, ROMOL_SPTR>& r = res[ri];
if (side_chains->getNumAtoms() == r.second->getNumAtoms() &&
side_chains->getNumBonds() == r.second->getNumBonds() &&
((NULL == core.get() && NULL == r.first.get()) ||
(NULL != core.get() && NULL != r.first.get() &&
core->getNumAtoms() == r.first->getNumAtoms() &&
core->getNumBonds() == r.first->getNumBonds()))) {
// ToDo accurate check:
// 1. compare hash code
if (computeMorganCodeHash(*side_chains) ==
computeMorganCodeHash(*r.second) &&
(NULL == core ||
computeMorganCodeHash(*core) == computeMorganCodeHash(*r.first))) {
// 2. final check to exclude hash collisions
// We decided that it does not neccessary to implement
resFound = true;
break;
}
}
}
if (!resFound)
res.push_back(std::pair<ROMOL_SPTR, ROMOL_SPTR>(core, side_chains)); //
#ifdef _DEBUG
else
std::cout << res.size() + 1 << " --- DUPLICATE Result FOUND --- ri=" << ri
<< "\n";
#endif
}