mirror of
https://github.com/rdkit/rdkit.git
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8aac978f1b
- Module to generate reaction fingerprints: structural FP for screening, difference FP for similarity search - Add some utility functions to simplify handling of reactions - Add new functionality to include agents in the reactions, some adaptions to parsers and writers had to be done - Supports intra-bond breaks in products now - Molecules with rxn role (atom property) can be parse as reaction now
820 lines
36 KiB
C++
820 lines
36 KiB
C++
// $Id$
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//
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// Copyright (c) 2014, Novartis Institutes for BioMedical Research Inc.
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// All rights reserved.
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//
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// Redistribution and use in source and binary forms, with or without
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// modification, are permitted provided that the following conditions are
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// met:
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//
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// * Redistributions of source code must retain the above copyright
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// notice, this list of conditions and the following disclaimer.
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// * Redistributions in binary form must reproduce the above
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// copyright notice, this list of conditions and the following
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// disclaimer in the documentation and/or other materials provided
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// with the distribution.
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// * Neither the name of Novartis Institutes for BioMedical Research Inc.
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// nor the names of its contributors may be used to endorse or promote
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// products derived from this software without specific prior written permission.
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//
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// THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS
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// "AS IS" AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT
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// LIMITED TO, THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR
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// A PARTICULAR PURPOSE ARE DISCLAIMED. IN NO EVENT SHALL THE COPYRIGHT
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// OWNER OR CONTRIBUTORS BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL,
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// SPECIAL, EXEMPLARY, OR CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT
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// LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES; LOSS OF USE,
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// DATA, OR PROFITS; OR BUSINESS INTERRUPTION) HOWEVER CAUSED AND ON ANY
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// THEORY OF LIABILITY, WHETHER IN CONTRACT, STRICT LIABILITY, OR TORT
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// (INCLUDING NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE
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// OF THIS SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.
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//
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#include <GraphMol/ChemReactions/Reaction.h>
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#include <GraphMol/Substruct/SubstructMatch.h>
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#include <GraphMol/QueryOps.h>
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#include <boost/dynamic_bitset.hpp>
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#include <boost/foreach.hpp>
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#include <map>
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#include <algorithm>
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#include <GraphMol/ChemTransforms/ChemTransforms.h>
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#include <GraphMol/Descriptors/MolDescriptors.h>
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#include <GraphMol/SmilesParse/SmilesWrite.h>
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#include "GraphMol/ChemReactions/ReactionRunner.h"
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#include <RDGeneral/Invariant.h>
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namespace RDKit {
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typedef std::vector<MatchVectType> VectMatchVectType;
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typedef std::vector< VectMatchVectType > VectVectMatchVectType;
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namespace ReactionRunnerUtils {
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//! returns whether or not all reactants matched
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bool getReactantMatches(const MOL_SPTR_VECT &reactants,
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const ChemicalReaction &rxn,
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VectVectMatchVectType &matchesByReactant)
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{
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PRECONDITION(reactants.size()==rxn.getNumReactantTemplates(),"reactant size mismatch");
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matchesByReactant.clear();
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matchesByReactant.resize(reactants.size());
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bool res=true;
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unsigned int i=0;
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for(MOL_SPTR_VECT::const_iterator iter = rxn.beginReactantTemplates();
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iter != rxn.endReactantTemplates(); ++iter, i++){
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std::vector< MatchVectType > matchesHere;
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// NOTE that we are *not* uniquifying the results.
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// This is because we need multiple matches in reactions. For example,
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// The ring-closure coded as:
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// [C:1]=[C:2] + [C:3]=[C:4][C:5]=[C:6] -> [C:1]1[C:2][C:3][C:4]=[C:5][C:6]1
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// should give 4 products here:
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// [Cl]C=C + [Br]C=CC=C ->
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// [Cl]C1C([Br])C=CCC1
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// [Cl]C1CC(Br)C=CC1
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// C1C([Br])C=CCC1[Cl]
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// C1CC([Br])C=CC1[Cl]
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// Yes, in this case there are only 2 unique products, but that's
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// a factor of the reactants' symmetry.
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//
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// There's no particularly straightforward way of solving this problem of recognizing cases
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// where we should give all matches and cases where we shouldn't; it's safer to just
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// produce everything and let the client deal with uniquifying their results.
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int matchCount=SubstructMatch(*(reactants[i]),*iter->get(), matchesHere, false, true, false);
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BOOST_FOREACH(const MatchVectType &match, matchesHere){
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bool keep=true;
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int pIdx,mIdx;
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BOOST_FOREACH(boost::tie(pIdx,mIdx),match){
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if(reactants[i]->getAtomWithIdx(mIdx)->hasProp("_protected")){
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keep=false;
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break;
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}
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}
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if(keep){
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matchesByReactant[i].push_back(match);
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} else {
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--matchCount;
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}
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}
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if(!matchCount){
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// no point continuing if we don't match one of the reactants:
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res=false;
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break;
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}
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}
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return res;
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} // end of getReactantMatches()
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void recurseOverReactantCombinations(const VectVectMatchVectType &matchesByReactant,
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VectVectMatchVectType &matchesPerProduct,
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unsigned int level,VectMatchVectType combination){
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unsigned int nReactants=matchesByReactant.size();
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RANGE_CHECK(0,level,nReactants-1);
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PRECONDITION(combination.size()==nReactants,"bad combination size");
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for(VectMatchVectType::const_iterator reactIt=matchesByReactant[level].begin();
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reactIt != matchesByReactant[level].end(); ++reactIt){
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VectMatchVectType prod=combination;
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prod[level] = *reactIt;
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if(level==nReactants-1){
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// this is the bottom of the recursion:
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matchesPerProduct.push_back(prod);
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} else {
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recurseOverReactantCombinations(matchesByReactant,matchesPerProduct,level+1,prod);
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}
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}
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} //end of recurseOverReactantCombinations
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void updateImplicitAtomProperties(Atom *prodAtom,const Atom *reactAtom){
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PRECONDITION(prodAtom,"no product atom");
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PRECONDITION(reactAtom,"no reactant atom");
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if(prodAtom->getAtomicNum()!=reactAtom->getAtomicNum()){
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// if we changed atom identity all bets are off, just
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// return
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return;
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}
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if(!prodAtom->hasProp("_QueryFormalCharge")){
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prodAtom->setFormalCharge(reactAtom->getFormalCharge());
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}
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if(!prodAtom->hasProp("_QueryIsotope")){
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prodAtom->setIsotope(reactAtom->getIsotope());
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}
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if(!prodAtom->hasProp("_ReactionDegreeChanged")){
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if(!prodAtom->hasProp("_QueryHCount")){
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prodAtom->setNumExplicitHs(reactAtom->getNumExplicitHs());
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}
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prodAtom->setNoImplicit(reactAtom->getNoImplicit());
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}
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}
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void generateReactantCombinations(const VectVectMatchVectType &matchesByReactant,
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VectVectMatchVectType &matchesPerProduct){
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matchesPerProduct.clear();
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VectMatchVectType tmp;
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tmp.clear();
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tmp.resize(matchesByReactant.size());
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recurseOverReactantCombinations(matchesByReactant,matchesPerProduct,0,tmp);
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} // end of generateReactantCombinations()
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RWMOL_SPTR initProduct(const ROMOL_SPTR prodTemplateSptr){
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const ROMol *prodTemplate=prodTemplateSptr.get();
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RWMol *res=new RWMol();
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// --------- --------- --------- --------- --------- ---------
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// Initialize by making a copy of the product template as a normal molecule.
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// NOTE that we can't just use a normal copy because we do not want to end up
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// with query atoms or bonds in the product.
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// copy in the atoms:
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ROMol::ATOM_ITER_PAIR atItP = prodTemplate->getVertices();
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while(atItP.first != atItP.second ){
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Atom *oAtom=(*prodTemplate)[*(atItP.first++)].get();
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Atom *newAtom=new Atom(*oAtom);
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res->addAtom(newAtom,false,true);
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if(newAtom->hasProp("molAtomMapNumber")){
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// set bookmarks for the mapped atoms:
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int mapNum;
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newAtom->getProp("molAtomMapNumber",mapNum);
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res->setAtomBookmark(newAtom,mapNum);
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// now clear the molAtomMapNumber property so that it doesn't
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// end up in the products (this was bug 3140490):
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newAtom->clearProp("molAtomMapNumber");
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}
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newAtom->setChiralTag(Atom::CHI_UNSPECIFIED);
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// if the product-template atom has the inversion flag set
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// to 4 (=SET), then bring its stereochem over, otherwise we'll
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// ignore it:
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if(oAtom->hasProp("molInversionFlag")){
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int iFlag;
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oAtom->getProp("molInversionFlag",iFlag);
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if(iFlag==4) newAtom->setChiralTag(oAtom->getChiralTag());
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}
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// check for properties we need to set:
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if(newAtom->hasProp("_QueryFormalCharge")){
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int val;
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newAtom->getProp("_QueryFormalCharge",val);
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newAtom->setFormalCharge(val);
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}
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if(newAtom->hasProp("_QueryHCount")){
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int val;
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newAtom->getProp("_QueryHCount",val);
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newAtom->setNumExplicitHs(val);
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}
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if(newAtom->hasProp("_QueryMass")){
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int val;
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newAtom->getProp("_QueryMass",val);
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newAtom->setMass(val);
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}
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if(newAtom->hasProp("_QueryIsotope")){
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int val;
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newAtom->getProp("_QueryIsotope",val);
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newAtom->setIsotope(val);
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}
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}
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// and the bonds:
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ROMol::BOND_ITER_PAIR bondItP = prodTemplate->getEdges();
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while(bondItP.first != bondItP.second ){
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const BOND_SPTR oldB=(*prodTemplate)[*(bondItP.first++)];
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unsigned int bondIdx;
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bondIdx=res->addBond(oldB->getBeginAtomIdx(),oldB->getEndAtomIdx(),oldB->getBondType())-1;
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// make sure we don't lose the bond dir information:
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Bond *newB=res->getBondWithIdx(bondIdx);
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newB->setBondDir(oldB->getBondDir());
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// Special case/hack:
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// The product has been processed by the SMARTS parser.
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// The SMARTS parser tags unspecified bonds as single, but then adds
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// a query so that they match single or double
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// This caused Issue 1748846
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// http://sourceforge.net/tracker/index.php?func=detail&aid=1748846&group_id=160139&atid=814650
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// We need to fix that little problem now:
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if( oldB->hasQuery()){
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// remember that the product has been processed by the SMARTS parser.
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std::string queryDescription=oldB->getQuery()->getDescription();
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if(queryDescription=="BondOr" &&
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oldB->getBondType()==Bond::SINGLE){
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// We need to fix that little problem now:
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if(newB->getBeginAtom()->getIsAromatic() && newB->getEndAtom()->getIsAromatic()){
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newB->setBondType(Bond::AROMATIC);
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newB->setIsAromatic(true);
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} else {
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newB->setBondType(Bond::SINGLE);
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newB->setIsAromatic(false);
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}
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} else if(queryDescription=="BondNull") {
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newB->setProp("NullBond",1);
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}
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}
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}
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return RWMOL_SPTR(res);
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} // end of initProduct()
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struct ReactantProductAtomMapping{
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ReactantProductAtomMapping(unsigned lenghtBitSet)
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{
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mappedAtoms.resize(lenghtBitSet);
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skippedAtoms.resize(lenghtBitSet);
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}
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boost::dynamic_bitset<> mappedAtoms;
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boost::dynamic_bitset<> skippedAtoms;
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std::map<unsigned int,std::vector<unsigned int> > reactProdAtomMap;
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std::map<unsigned int,unsigned int> prodReactAtomMap;
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std::map<unsigned int,unsigned int> prodAtomBondMap;
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};
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ReactantProductAtomMapping* getAtomMappingsReactantProduct(const MatchVectType &match,
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const ROMol& reactantTemplate, RWMOL_SPTR product, unsigned numReactAtoms)
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{
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ReactantProductAtomMapping *mapping = new ReactantProductAtomMapping(numReactAtoms);
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for(unsigned int i=0;i<match.size();i++){
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const Atom *templateAtom=reactantTemplate.getAtomWithIdx(match[i].first);
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if(templateAtom->hasProp("molAtomMapNumber")){
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int molAtomMapNumber;
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templateAtom->getProp("molAtomMapNumber",molAtomMapNumber);
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if(product->hasAtomBookmark(molAtomMapNumber)){
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RWMol::ATOM_PTR_LIST atomIdxs = product->getAllAtomsWithBookmark(molAtomMapNumber);
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for(RWMol::ATOM_PTR_LIST::iterator iter = atomIdxs.begin();
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iter != atomIdxs.end(); ++iter){
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Atom * a = *iter;
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unsigned int pIdx = a->getIdx();
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mapping->reactProdAtomMap[match[i].second].push_back(pIdx);
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mapping->mappedAtoms[match[i].second]=1;
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CHECK_INVARIANT(pIdx<product->getNumAtoms(),"yikes!");
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mapping->prodReactAtomMap[pIdx]=match[i].second;
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}
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}
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else {
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// this skippedAtom has an atomMapNumber, but it's not in this product
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// (it's either in another product or it's not mapped at all).
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mapping->skippedAtoms[match[i].second]=1;
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}
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}
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else {
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// This skippedAtom appears in the match, but not in a product:
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mapping->skippedAtoms[match[i].second]=1;
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}
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}
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return mapping;
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}
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void setReactantBondPropertiesToProduct(RWMOL_SPTR product, const ROMol& reactant,
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ReactantProductAtomMapping* mapping)
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{
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ROMol::BOND_ITER_PAIR bondItP = product->getEdges();
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while(bondItP.first != bondItP.second ){
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BOND_SPTR pBond=(*product)[*(bondItP.first)];
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++bondItP.first;
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if(pBond->hasProp("NullBond")){
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if(mapping->prodReactAtomMap.find(pBond->getBeginAtomIdx())!=mapping->prodReactAtomMap.end() &&
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mapping->prodReactAtomMap.find(pBond->getEndAtomIdx())!=mapping->prodReactAtomMap.end() ){
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// the bond is between two mapped atoms from this reactant:
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unsigned begIdx = mapping->prodReactAtomMap[pBond->getBeginAtomIdx()];
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unsigned endIdx = mapping->prodReactAtomMap[pBond->getEndAtomIdx()];
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const Bond *rBond=reactant.getBondBetweenAtoms(begIdx,endIdx);
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if(!rBond) continue;
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pBond->setBondType(rBond->getBondType());
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pBond->setBondDir(rBond->getBondDir());
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pBond->setIsAromatic(rBond->getIsAromatic());
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pBond->clearProp("NullBond");
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}
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}
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}
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}
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void checkProductChirality(Atom::ChiralType reactantChirality, Atom *productAtom)
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{
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int flagVal;
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productAtom->getProp("molInversionFlag",flagVal);
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switch(flagVal){
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case 0:
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// FIX: should we clear the chirality or leave it alone? for now we leave it alone
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//productAtom->setChiralTag(Atom::ChiralType::CHI_UNSPECIFIED);
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productAtom->setChiralTag(reactantChirality);
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break;
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case 1:
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// inversion
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if(reactantChirality!=Atom::CHI_TETRAHEDRAL_CW && reactantChirality!=Atom::CHI_TETRAHEDRAL_CCW){
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BOOST_LOG(rdWarningLog) << "unsupported chiral type on reactant atom ignored\n";
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}
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else {
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productAtom->setChiralTag(reactantChirality);
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productAtom->invertChirality();
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}
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break;
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case 2:
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// retention: just set to the reactant
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productAtom->setChiralTag(reactantChirality);
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break;
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case 3:
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// remove stereo
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productAtom->setChiralTag(Atom::CHI_UNSPECIFIED);
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break;
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case 4:
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// set stereo, so leave it the way it was in the product template
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break;
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default:
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BOOST_LOG(rdWarningLog) << "unrecognized chiral inversion/retention flag on product atom ignored\n";
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}
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}
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void setReactantAtomPropertiesToProduct(
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Atom *productAtom, const Atom& reactantAtom,
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bool setImplicitProperties)
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{
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// which properties need to be set from the reactant?
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if(productAtom->getAtomicNum()<=0){
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productAtom->setAtomicNum(reactantAtom.getAtomicNum());
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productAtom->setIsAromatic(reactantAtom.getIsAromatic());
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// don't copy isotope information over from dummy atoms
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productAtom->setIsotope(reactantAtom.getIsotope());
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// remove dummy labels (if present)
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if(productAtom->hasProp("dummyLabel")) productAtom->clearProp("dummyLabel");
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if(productAtom->hasProp("_MolFileRLabel")) productAtom->clearProp("_MolFileRLabel");
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}
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if(setImplicitProperties){
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updateImplicitAtomProperties(productAtom,&reactantAtom);
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}
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// One might be tempted to copy over the reactant atom's chirality into the
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// product atom if chirality is not specified on the product. This would be a
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// very bad idea because the order of bonds will almost certainly change on the
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// atom and the chirality is referenced to bond order.
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// --------- --------- --------- --------- --------- ---------
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// While we're here, set the stereochemistry
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// FIX: this should be free-standing, not in this function.
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if(reactantAtom.getChiralTag()!=Atom::CHI_UNSPECIFIED &&
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reactantAtom.getChiralTag()!=Atom::CHI_OTHER &&
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productAtom->hasProp("molInversionFlag")){
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checkProductChirality(reactantAtom.getChiralTag(), productAtom);
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}
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}
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void setNewProductBond(const Bond& origB, RWMOL_SPTR product,
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unsigned bondBeginIdx, unsigned bondEndIdx)
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{
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unsigned bondIdx = product->addBond(bondBeginIdx, bondEndIdx, origB.getBondType())-1;
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Bond *newB = product->getBondWithIdx(bondIdx);
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newB->setBondDir(origB.getBondDir());
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}
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void addMissingProductBonds(const Bond& origB, RWMOL_SPTR product,
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ReactantProductAtomMapping* mapping)
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{
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unsigned int begIdx=origB.getBeginAtomIdx();
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unsigned int endIdx=origB.getEndAtomIdx();
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std::vector<unsigned> prodBeginIdxs = mapping->reactProdAtomMap[begIdx];
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std::vector<unsigned> prodEndIdxs = mapping->reactProdAtomMap[endIdx];
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CHECK_INVARIANT(prodBeginIdxs.size() == prodEndIdxs.size(),
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"Different number of start-end points for product bonds.");
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for(unsigned i = 0; i < prodBeginIdxs.size(); i++){
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setNewProductBond(origB, product, prodBeginIdxs.at(i), prodEndIdxs.at(i));
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}
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}
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void addMissingProductAtom(const Atom& reactAtom, unsigned reactNeighborIdx,
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unsigned prodNeighborIdx, RWMOL_SPTR product, const ROMol& reactant,
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ReactantProductAtomMapping* mapping)
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{
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Atom *newAtom = new Atom(reactAtom);
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unsigned reactAtomIdx = reactAtom.getIdx();
|
|
unsigned productIdx = product->addAtom(newAtom,false,true);
|
|
mapping->reactProdAtomMap[reactAtomIdx].push_back(productIdx);
|
|
mapping->prodReactAtomMap[productIdx] = reactAtomIdx;
|
|
// add the bonds
|
|
const Bond *origB = reactant.getBondBetweenAtoms(reactNeighborIdx,reactAtomIdx);
|
|
unsigned int begIdx=origB->getBeginAtomIdx();
|
|
unsigned int endIdx=origB->getEndAtomIdx();
|
|
if(begIdx == reactNeighborIdx){
|
|
setNewProductBond(*origB, product, prodNeighborIdx, productIdx);
|
|
}
|
|
else{
|
|
setNewProductBond(*origB, product, productIdx, prodNeighborIdx);
|
|
}
|
|
}
|
|
|
|
|
|
void addReactantNeighborsToProduct(const ROMol& reactant, const Atom& reactantAtom,
|
|
RWMOL_SPTR product, boost::dynamic_bitset<>& visitedAtoms,
|
|
std::vector<const Atom*>& chiralAtomsToCheck,
|
|
ReactantProductAtomMapping* mapping)
|
|
{
|
|
std::list<const Atom*> atomStack;
|
|
atomStack.push_back(&reactantAtom);
|
|
while(!atomStack.empty()){
|
|
const Atom *lReactantAtom = atomStack.front();
|
|
atomStack.pop_front();
|
|
|
|
// each atom in the stack is guaranteed to already be in the product:
|
|
CHECK_INVARIANT(mapping->reactProdAtomMap.find(lReactantAtom->getIdx()) !=
|
|
mapping->reactProdAtomMap.end(),
|
|
"reactant atom on traversal stack not present in product.");
|
|
|
|
std::vector<unsigned> lReactantAtomProductIndex =
|
|
mapping->reactProdAtomMap[lReactantAtom->getIdx()];
|
|
unsigned lreactIdx = lReactantAtom->getIdx();
|
|
visitedAtoms[lreactIdx] = 1;
|
|
// Check our neighbors:
|
|
ROMol::ADJ_ITER nbrIdx,endNbrs;
|
|
boost::tie(nbrIdx,endNbrs) = reactant.getAtomNeighbors(lReactantAtom);
|
|
while(nbrIdx!=endNbrs){
|
|
// Four possibilities here. The neighbor:
|
|
// 0) has been visited already: do nothing
|
|
// 1) is part of the match (thus already in the product): set a bond to it
|
|
// 2) has been added: set a bond to it
|
|
// 3) has not yet been added: add it, set a bond to it, and push it
|
|
// onto the stack
|
|
if(!visitedAtoms[*nbrIdx] && !mapping->skippedAtoms[*nbrIdx]){
|
|
if(mapping->mappedAtoms[*nbrIdx]){
|
|
// this is case 1 (neighbor in match); set a bond to the neighbor if this atom
|
|
// is not also in the match (match-match bonds were set when the product template was
|
|
// copied in to start things off).;
|
|
if(!mapping->mappedAtoms[lreactIdx]){
|
|
CHECK_INVARIANT(mapping->reactProdAtomMap.find(*nbrIdx)!=mapping->reactProdAtomMap.end(),
|
|
"reactant atom not present in product.");
|
|
const Bond *origB=reactant.getBondBetweenAtoms(lreactIdx,*nbrIdx);
|
|
addMissingProductBonds(*origB, product,mapping);
|
|
}
|
|
}
|
|
else if(mapping->reactProdAtomMap.find(*nbrIdx)!= mapping->reactProdAtomMap.end()){
|
|
// case 2, the neighbor has been added and we just need to set a bond to it:
|
|
const Bond *origB=reactant.getBondBetweenAtoms(lreactIdx,*nbrIdx);
|
|
addMissingProductBonds(*origB, product,mapping);
|
|
}
|
|
else {
|
|
// case 3, add the atom, a bond to it, and push the atom onto the stack
|
|
const Atom *neighbor=reactant.getAtomWithIdx(*nbrIdx);
|
|
for(unsigned i = 0; i < lReactantAtomProductIndex.size(); i++){
|
|
addMissingProductAtom(*neighbor, lreactIdx,lReactantAtomProductIndex[i],
|
|
product, reactant, mapping);
|
|
}
|
|
// update the stack:
|
|
atomStack.push_back(neighbor);
|
|
// if the atom is chiral, we need to check its bond ordering later:
|
|
if(neighbor->getChiralTag()!=Atom::CHI_UNSPECIFIED){
|
|
chiralAtomsToCheck.push_back(neighbor);
|
|
}
|
|
}
|
|
}
|
|
nbrIdx++;
|
|
}
|
|
} // end of atomStack traversal
|
|
}
|
|
|
|
void checkAndCorrectChiralityOfMatchingAtomsInProduct(
|
|
const ROMol& reactant, unsigned reactantAtomIdx,
|
|
const Atom& reactantAtom, RWMOL_SPTR product,
|
|
ReactantProductAtomMapping* mapping)
|
|
{
|
|
for(unsigned i = 0; i < mapping->reactProdAtomMap[reactantAtomIdx].size(); i++){
|
|
unsigned productAtomIdx = mapping->reactProdAtomMap[reactantAtomIdx][i];
|
|
Atom *productAtom = product->getAtomWithIdx(productAtomIdx);
|
|
|
|
if(productAtom->getChiralTag() != Atom::CHI_UNSPECIFIED ||
|
|
reactantAtom.getChiralTag() == Atom::CHI_UNSPECIFIED ||
|
|
reactantAtom.getChiralTag() == Atom::CHI_OTHER ||
|
|
productAtom->hasProp("molInversionFlag")){
|
|
continue;
|
|
}
|
|
// we can only do something sensible here if we have the same number of bonds
|
|
// in the reactants and the products:
|
|
if(reactantAtom.getDegree() != productAtom->getDegree()){
|
|
continue;
|
|
}
|
|
unsigned int nUnknown=0;
|
|
INT_LIST pOrder;
|
|
ROMol::ADJ_ITER nbrIdx,endNbrs;
|
|
boost::tie(nbrIdx,endNbrs) = product->getAtomNeighbors(productAtom);
|
|
while(nbrIdx != endNbrs){
|
|
if(mapping->prodReactAtomMap.find(*nbrIdx) == mapping->prodReactAtomMap.end()){
|
|
++nUnknown;
|
|
// if there's more than one bond in the product that doesn't correspond to
|
|
// anything in the reactant, we're also doomed
|
|
if(nUnknown > 1) break;
|
|
// otherwise, add a -1 to the bond order that we'll fill in later
|
|
pOrder.push_back(-1);
|
|
}
|
|
else {
|
|
const Bond *rBond=reactant.getBondBetweenAtoms(reactantAtom.getIdx(),mapping->prodReactAtomMap[*nbrIdx]);
|
|
CHECK_INVARIANT(rBond,"expected reactant bond not found");
|
|
pOrder.push_back(rBond->getIdx());
|
|
}
|
|
++nbrIdx;
|
|
}
|
|
if(nUnknown == 1){
|
|
// find the reactant bond that hasn't yet been accounted for:
|
|
int unmatchedBond = -1;
|
|
boost::tie(nbrIdx,endNbrs) = reactant.getAtomNeighbors(&reactantAtom);
|
|
while(nbrIdx!=endNbrs){
|
|
const Bond *rBond=reactant.getBondBetweenAtoms(reactantAtom.getIdx(),*nbrIdx);
|
|
if(std::find(pOrder.begin(),pOrder.end(),rBond->getIdx()) == pOrder.end()){
|
|
unmatchedBond = rBond->getIdx();
|
|
break;
|
|
}
|
|
++nbrIdx;
|
|
}
|
|
// what must be true at this point:
|
|
// 1) there's a -1 in pOrder that we'll substitute for
|
|
// 2) unmatchedBond contains the index of the substitution
|
|
INT_LIST::iterator bPos=std::find(pOrder.begin(),pOrder.end(),-1);
|
|
if(unmatchedBond >= 0 && bPos != pOrder.end()){
|
|
*bPos = unmatchedBond;
|
|
}
|
|
if(std::find(pOrder.begin(),pOrder.end(),-1) == pOrder.end()){
|
|
nUnknown = 0;
|
|
}
|
|
}
|
|
if(!nUnknown){
|
|
productAtom->setChiralTag(reactantAtom.getChiralTag());
|
|
int nSwaps = reactantAtom.getPerturbationOrder(pOrder);
|
|
if(nSwaps%2){
|
|
productAtom->invertChirality();
|
|
}
|
|
}
|
|
}
|
|
}
|
|
|
|
void checkAndCorrectChiralityOfProduct(const std::vector<const Atom*>& chiralAtomsToCheck,
|
|
RWMOL_SPTR product, ReactantProductAtomMapping* mapping)
|
|
{
|
|
for(std::vector<const Atom *>::const_iterator atomIt = chiralAtomsToCheck.begin();
|
|
atomIt != chiralAtomsToCheck.end(); ++atomIt){
|
|
const Atom *reactantAtom = *atomIt;
|
|
CHECK_INVARIANT(reactantAtom->getChiralTag()!=Atom::CHI_UNSPECIFIED,
|
|
"missing atom chirality.");
|
|
unsigned int reactAtomDegree = reactantAtom->getOwningMol().getAtomDegree(reactantAtom);
|
|
for(unsigned i = 0; i < mapping->reactProdAtomMap[reactantAtom->getIdx()].size(); i++){
|
|
unsigned productAtomIdx = mapping->reactProdAtomMap[reactantAtom->getIdx()][i];
|
|
Atom *productAtom = product->getAtomWithIdx(productAtomIdx);
|
|
CHECK_INVARIANT(reactantAtom->getChiralTag() == productAtom->getChiralTag(),
|
|
"invalid product chirality.");
|
|
|
|
if(reactAtomDegree != product->getAtomDegree(productAtom) ){
|
|
// If the number of bonds to the atom has changed in the course of the
|
|
// reaction we're lost, so remove chirality.
|
|
// A word of explanation here: the atoms in the chiralAtomsToCheck set are
|
|
// not explicitly mapped atoms of the reaction, so we really have no idea what
|
|
// to do with this case. At the moment I'm not even really sure how this
|
|
// could happen, but better safe than sorry.
|
|
productAtom->setChiralTag(Atom::CHI_UNSPECIFIED);
|
|
}
|
|
else if(reactantAtom->getChiralTag() == Atom::CHI_TETRAHEDRAL_CW ||
|
|
reactantAtom->getChiralTag() == Atom::CHI_TETRAHEDRAL_CCW){
|
|
// this will contain the indices of product bonds in the
|
|
// reactant order:
|
|
INT_LIST newOrder;
|
|
ROMol::OEDGE_ITER beg,end;
|
|
boost::tie(beg,end) = reactantAtom->getOwningMol().getAtomBonds(reactantAtom);
|
|
while(beg!=end){
|
|
const BOND_SPTR reactantBond = reactantAtom->getOwningMol()[*beg];
|
|
unsigned int oAtomIdx = reactantBond->getOtherAtomIdx(reactantAtom->getIdx());
|
|
CHECK_INVARIANT(mapping->reactProdAtomMap.find(oAtomIdx) != mapping->reactProdAtomMap.end(),
|
|
"other atom from bond not mapped.");
|
|
const Bond *productBond;
|
|
unsigned neighborBondIdx = mapping->reactProdAtomMap[oAtomIdx][i];
|
|
productBond = product->getBondBetweenAtoms(productAtom->getIdx(),neighborBondIdx);
|
|
CHECK_INVARIANT(productBond,"no matching bond found in product");
|
|
newOrder.push_back(productBond->getIdx());
|
|
++beg;
|
|
}
|
|
int nSwaps=productAtom->getPerturbationOrder(newOrder);
|
|
if(nSwaps%2){
|
|
productAtom->invertChirality();
|
|
}
|
|
}
|
|
else {
|
|
// not tetrahedral chirality, don't do anything.
|
|
}
|
|
}
|
|
} // end of loop over chiralAtomsToCheck
|
|
}
|
|
|
|
void generateProductConformers(Conformer *productConf, const ROMol& reactant,
|
|
ReactantProductAtomMapping* mapping)
|
|
{
|
|
if(!reactant.getNumConformers()){
|
|
return;
|
|
}
|
|
const Conformer &reactConf=reactant.getConformer();
|
|
if(reactConf.is3D()){
|
|
productConf->set3D(true);
|
|
}
|
|
for(std::map<unsigned int, std::vector<unsigned int> >::const_iterator pr = mapping->reactProdAtomMap.begin();
|
|
pr!=mapping->reactProdAtomMap.end();++pr){
|
|
std::vector<unsigned> prodIdxs = pr->second;
|
|
if(prodIdxs.size()>1){
|
|
BOOST_LOG(rdWarningLog) << "reactant atom match more than one product atom, coordinates need to be revised\n";
|
|
}
|
|
// is this reliable when multiple product atom mapping occurs????
|
|
for(unsigned i = 0; i < prodIdxs.size(); i++){
|
|
productConf->setAtomPos(prodIdxs[i],reactConf.getAtomPos(pr->first));
|
|
}
|
|
}
|
|
}
|
|
|
|
|
|
void addReactantAtomsAndBonds(const ChemicalReaction& rxn,
|
|
RWMOL_SPTR product,const ROMOL_SPTR reactantSptr,
|
|
const MatchVectType &match,
|
|
const ROMOL_SPTR reactantTemplate,
|
|
Conformer *productConf)
|
|
{
|
|
// start by looping over all matches and marking the reactant atoms that
|
|
// have already been "added" by virtue of being in the product. We'll also
|
|
// mark "skipped" atoms: those that are in the match, but not in this
|
|
// particular product (or, perhaps, not in any product)
|
|
// At the same time we'll set up a map between the indices of those
|
|
// atoms and their index in the product.
|
|
ReactantProductAtomMapping* mapping =
|
|
getAtomMappingsReactantProduct(match,*reactantTemplate,product,reactantSptr->getNumAtoms());
|
|
|
|
boost::dynamic_bitset<> visitedAtoms(reactantSptr->getNumAtoms());
|
|
|
|
const ROMol *reactant=reactantSptr.get();
|
|
|
|
// ---------- ---------- ---------- ---------- ---------- ----------
|
|
// Loop over the bonds in the product and look for those that have
|
|
// the NullBond property set. These are bonds for which no information
|
|
// (other than their existance) was provided in the template:
|
|
setReactantBondPropertiesToProduct(product, *reactant, mapping);
|
|
|
|
// ---------- ---------- ---------- ---------- ---------- ----------
|
|
// Loop over the atoms in the match that were added to the product
|
|
// From the corresponding atom in the reactant, do a graph traversal
|
|
// to find other connected atoms that should be added:
|
|
|
|
std::vector<const Atom *> chiralAtomsToCheck;
|
|
for(unsigned matchIdx=0; matchIdx<match.size(); matchIdx++){
|
|
|
|
int reactantAtomIdx = match[matchIdx].second;
|
|
if(mapping->mappedAtoms[reactantAtomIdx]){
|
|
CHECK_INVARIANT(mapping->reactProdAtomMap.find(reactantAtomIdx)!=mapping->reactProdAtomMap.end(),
|
|
"mapped reactant atom not present in product.");
|
|
|
|
const Atom *reactantAtom=reactant->getAtomWithIdx(reactantAtomIdx);
|
|
for(unsigned i = 0; i < mapping->reactProdAtomMap[reactantAtomIdx].size(); i++){
|
|
// here's a pointer to the atom in the product:
|
|
unsigned productAtomIdx = mapping->reactProdAtomMap[reactantAtomIdx][i];
|
|
Atom *productAtom = product->getAtomWithIdx(productAtomIdx);
|
|
setReactantAtomPropertiesToProduct(productAtom, *reactantAtom,rxn.getImplicitPropertiesFlag());
|
|
}
|
|
// now traverse:
|
|
addReactantNeighborsToProduct(*reactant, *reactantAtom, product, visitedAtoms,
|
|
chiralAtomsToCheck, mapping);
|
|
|
|
// now that we've added all the reactant's neighbors, check to see if
|
|
// it is chiral in the reactant but is not in the reaction. If so
|
|
// we need to worry about its chirality
|
|
checkAndCorrectChiralityOfMatchingAtomsInProduct(*reactant, reactantAtomIdx, *reactantAtom, product, mapping);
|
|
}
|
|
} // end of loop over matched atoms
|
|
|
|
// ---------- ---------- ---------- ---------- ---------- ----------
|
|
// now we need to loop over atoms from the reactants that were chiral but not
|
|
// directly involved in the reaction in order to make sure their chirality hasn't
|
|
// been disturbed
|
|
checkAndCorrectChiralityOfProduct(chiralAtomsToCheck, product, mapping);
|
|
|
|
// ---------- ---------- ---------- ---------- ---------- ----------
|
|
// finally we may need to set the coordinates in the product conformer:
|
|
if(productConf){
|
|
productConf->resize(product->getNumAtoms());
|
|
generateProductConformers(productConf, *reactant, mapping);
|
|
}
|
|
} // end of addReactantAtomsAndBonds
|
|
|
|
|
|
MOL_SPTR_VECT generateOneProductSet(const ChemicalReaction& rxn,
|
|
const MOL_SPTR_VECT& reactants,
|
|
const std::vector<MatchVectType> &reactantsMatch)
|
|
{
|
|
PRECONDITION(reactants.size() == reactantsMatch.size(),"vector size mismatch");
|
|
|
|
// if any of the reactants have a conformer, we'll go ahead and
|
|
// generate conformers for the products:
|
|
bool doConfs=false;
|
|
BOOST_FOREACH(ROMOL_SPTR reactant,reactants){
|
|
if(reactant->getNumConformers()){
|
|
doConfs=true;
|
|
break;
|
|
}
|
|
}
|
|
|
|
MOL_SPTR_VECT res;
|
|
res.resize(rxn.getNumProductTemplates());
|
|
unsigned int prodId=0;
|
|
for(MOL_SPTR_VECT::const_iterator pTemplIt = rxn.beginProductTemplates();
|
|
pTemplIt != rxn.endProductTemplates(); ++pTemplIt){
|
|
// copy product template and its properties to a new product RWMol
|
|
RWMOL_SPTR product = initProduct(*pTemplIt);
|
|
Conformer *conf = 0;
|
|
if(doConfs){
|
|
conf = new Conformer();
|
|
conf->set3D(false);
|
|
}
|
|
|
|
unsigned int reactantId = 0;
|
|
for(MOL_SPTR_VECT::const_iterator iter = rxn.beginReactantTemplates();
|
|
iter != rxn.endReactantTemplates(); ++iter, reactantId++){
|
|
addReactantAtomsAndBonds(rxn, product, reactants.at(reactantId),
|
|
reactantsMatch.at(reactantId),
|
|
*iter, conf);
|
|
}
|
|
product->clearAllAtomBookmarks();
|
|
if(doConfs){
|
|
product->addConformer(conf,true);
|
|
}
|
|
res[prodId] = product;
|
|
++prodId;
|
|
}
|
|
return res;
|
|
}
|
|
}// end namespace RectionRunnerUtils
|
|
|
|
std::vector<MOL_SPTR_VECT> run_Reactants(const ChemicalReaction& rxn, const MOL_SPTR_VECT& reactants) {
|
|
if(!rxn.isInitialized()) {
|
|
throw ChemicalReactionException("initMatchers() must be called before runReactants()");
|
|
}
|
|
if(reactants.size() != rxn.getNumReactantTemplates()){
|
|
throw ChemicalReactionException("Number of reactants provided does not match number of reactant templates.");
|
|
}
|
|
BOOST_FOREACH(ROMOL_SPTR msptr,reactants){
|
|
CHECK_INVARIANT(msptr,"bad molecule in reactants");
|
|
}
|
|
|
|
std::vector<MOL_SPTR_VECT> productMols;
|
|
productMols.clear();
|
|
|
|
// if we have no products, return now:
|
|
if(!rxn.getNumProductTemplates()){
|
|
return productMols;
|
|
}
|
|
|
|
// find the matches for each reactant:
|
|
VectVectMatchVectType matchesByReactant;
|
|
if(!ReactionRunnerUtils::getReactantMatches(reactants, rxn, matchesByReactant)){
|
|
// some reactants didn't find a match, return an empty product list:
|
|
return productMols;
|
|
}
|
|
// -------------------------------------------------------
|
|
// we now have matches for each reactant, so we can start creating products:
|
|
// start by doing the combinatorics on the matches:
|
|
VectVectMatchVectType reactantMatchesPerProduct;
|
|
ReactionRunnerUtils::generateReactantCombinations(matchesByReactant,reactantMatchesPerProduct);
|
|
productMols.resize(reactantMatchesPerProduct.size());
|
|
|
|
for(unsigned int productId=0;productId!=productMols.size();++productId){
|
|
MOL_SPTR_VECT lProds = ReactionRunnerUtils::generateOneProductSet(rxn, reactants,reactantMatchesPerProduct[productId]);
|
|
productMols[productId]=lProds;
|
|
}
|
|
|
|
return productMols;
|
|
} // end of ChemicalReaction::runReactants()
|
|
|
|
|
|
} // end of RDKit namespace
|