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d033aee043
* add id members to StereoGroup class * add optional read id argument to StereoGroup constructors * add functions forward Stereo Group Ids and assign the missing ones * update ops updating stereogroups to forward read id * update CX Smiles to parse/write stereogroup ids * Add test cases for stereo group id forwarding/canonicalization * update mol block (V3K only) to parse/write stereogroup ids * update pickling to parse/write stereogroup ids * update cdxml parser to store stereogroup ids * update mol interchange to parse/write stereogroup ids * update draw code with new stere group ids * update test * add some tests * Update Code/GraphMol/Wrap/rdmolfiles.cpp Co-authored-by: Greg Landrum <greg.landrum@gmail.com> * Update Code/GraphMol/Wrap/rdmolfiles.cpp Co-authored-by: Greg Landrum <greg.landrum@gmail.com> * Update Code/GraphMol/Canon.cpp Co-authored-by: Greg Landrum <greg.landrum@gmail.com> * Update Code/GraphMol/SmilesParse/CXSmilesOps.cpp Co-authored-by: Greg Landrum <greg.landrum@gmail.com> * review --------- Co-authored-by: Greg Landrum <greg.landrum@gmail.com>
3121 lines
112 KiB
C++
3121 lines
112 KiB
C++
//
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// Copyright (C) 2004-2021 Greg Landrum and other RDKit contributors
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//
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// @@ All Rights Reserved @@
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// This file is part of the RDKit.
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// The contents are covered by the terms of the BSD license
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// which is included in the file license.txt, found at the root
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// of the RDKit source tree.
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//
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#include <GraphMol/RDKitBase.h>
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#include <RDGeneral/Ranking.h>
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#include <GraphMol/new_canon.h>
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#include <GraphMol/QueryOps.h>
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#include <RDGeneral/types.h>
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#include <sstream>
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#include <set>
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#include <algorithm>
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#include <RDGeneral/utils.h>
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#include <RDGeneral/Invariant.h>
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#include <RDGeneral/RDLog.h>
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#include <boost/dynamic_bitset.hpp>
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#include <Geometry/point.h>
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#include "Chirality.h"
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#include <cstdlib>
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#include <utility>
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// #define VERBOSE_CANON 1
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namespace RDKit {
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namespace {
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bool shouldDetectDoubleBondStereo(const Bond *bond) {
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const RingInfo *ri = bond->getOwningMol().getRingInfo();
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return (!ri->numBondRings(bond->getIdx()) ||
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ri->minBondRingSize(bond->getIdx()) >=
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Chirality::minRingSizeForDoubleBondStereo);
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}
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bool getValFromEnvironment(const char *var, bool defVal) {
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auto evar = std::getenv(var);
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if (evar != nullptr) {
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if (!strcmp(evar, "0")) {
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return false;
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} else {
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return true;
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}
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}
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return defVal;
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}
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bool is_regular_h(const Atom &atom) {
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return atom.getAtomicNum() == 1 && atom.getIsotope() == 0;
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}
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Bond::BondDir getOppositeBondDir(Bond::BondDir dir) {
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PRECONDITION(dir == Bond::ENDDOWNRIGHT || dir == Bond::ENDUPRIGHT,
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"bad bond direction");
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switch (dir) {
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case Bond::ENDDOWNRIGHT:
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return Bond::ENDUPRIGHT;
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case Bond::ENDUPRIGHT:
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return Bond::ENDDOWNRIGHT;
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default:
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return Bond::NONE;
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}
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}
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void setBondDirRelativeToAtom(Bond *bond, Atom *atom, Bond::BondDir dir,
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bool reverse, boost::dynamic_bitset<> &) {
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PRECONDITION(bond, "bad bond");
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PRECONDITION(atom, "bad atom");
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PRECONDITION(dir == Bond::ENDUPRIGHT || dir == Bond::ENDDOWNRIGHT, "bad dir");
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PRECONDITION(atom == bond->getBeginAtom() || atom == bond->getEndAtom(),
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"atom doesn't belong to bond");
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if (bond->getBeginAtom() != atom) {
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reverse = !reverse;
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}
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if (reverse) {
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dir = (dir == Bond::ENDUPRIGHT ? Bond::ENDDOWNRIGHT : Bond::ENDUPRIGHT);
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}
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// to ensure maximum compatibility, even when a bond has unknown stereo (set
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// explicitly and recorded in _UnknownStereo property), I will still let a
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// direction to be computed. You must check the _UnknownStereo property to
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// make sure whether this bond is explicitly set to have no direction info.
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// This makes sense because the direction info are all derived from
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// coordinates, the _UnknownStereo property is like extra metadata to be
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// used with the direction info.
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bond->setBondDir(dir);
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}
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bool isLinearArrangement(const RDGeom::Point3D &v1, const RDGeom::Point3D &v2) {
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double lsq = v1.lengthSq() * v2.lengthSq();
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// treat zero length vectors as linear
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if (lsq < 1.0e-6) {
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return true;
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}
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double dotProd = v1.dotProduct(v2);
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double cos178 =
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-0.999388; // == cos(M_PI-0.035), corresponds to a tolerance of 2 degrees
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return dotProd < cos178 * sqrt(lsq);
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}
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void controllingBondFromAtom(const ROMol &mol,
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const boost::dynamic_bitset<> &needsDir,
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const std::vector<unsigned int> &singleBondCounts,
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const Bond *dblBond, const Atom *atom, Bond *&bond,
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Bond *&obond, bool &squiggleBondSeen,
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bool &doubleBondSeen) {
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bond = nullptr;
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obond = nullptr;
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for (const auto tBond : mol.atomBonds(atom)) {
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if (tBond == dblBond) {
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continue;
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}
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if (tBond->getBondType() == Bond::SINGLE ||
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tBond->getBondType() == Bond::AROMATIC) {
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// prefer bonds that already have their directionality set
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// or that are adjacent to more double bonds:
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if (!bond) {
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bond = tBond;
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} else if (needsDir[tBond->getIdx()]) {
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if (singleBondCounts[tBond->getIdx()] >
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singleBondCounts[bond->getIdx()]) {
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obond = bond;
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bond = tBond;
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} else {
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obond = tBond;
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}
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} else {
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obond = bond;
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bond = tBond;
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}
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} else if (tBond->getBondType() == Bond::DOUBLE) {
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doubleBondSeen = true;
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}
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int explicit_unknown_stereo;
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if ((tBond->getBondType() == Bond::SINGLE ||
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tBond->getBondType() == Bond::AROMATIC) &&
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(tBond->getBondDir() == Bond::UNKNOWN ||
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((tBond->getPropIfPresent<int>(common_properties::_UnknownStereo,
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explicit_unknown_stereo) &&
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explicit_unknown_stereo)))) {
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squiggleBondSeen = true;
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break;
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}
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}
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}
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void updateDoubleBondNeighbors(ROMol &mol, Bond *dblBond, const Conformer *conf,
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boost::dynamic_bitset<> &needsDir,
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std::vector<unsigned int> &singleBondCounts,
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const VECT_INT_VECT &singleBondNbrs) {
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// we want to deal only with double bonds:
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PRECONDITION(dblBond, "bad bond");
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PRECONDITION(dblBond->getBondType() == Bond::DOUBLE, "not a double bond");
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if (!needsDir[dblBond->getIdx()]) {
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return;
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}
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needsDir.set(dblBond->getIdx(), 0);
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#if 0
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std::cerr << "**********************\n";
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std::cerr << "**********************\n";
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std::cerr << "**********************\n";
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std::cerr << "UDBN: " << dblBond->getIdx() << " "
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<< dblBond->getBeginAtomIdx() << "=" << dblBond->getEndAtomIdx()
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<< "\n";
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#endif
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std::vector<Bond *> followupBonds;
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Bond *bond1 = nullptr, *obond1 = nullptr;
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bool squiggleBondSeen = false;
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bool doubleBondSeen = false;
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controllingBondFromAtom(mol, needsDir, singleBondCounts, dblBond,
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dblBond->getBeginAtom(), bond1, obond1,
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squiggleBondSeen, doubleBondSeen);
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// Don't do any direction setting if we've seen a squiggle bond, but do mark
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// the double bond as a crossed bond and return
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if (!bond1 || squiggleBondSeen || doubleBondSeen) {
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if (!doubleBondSeen) {
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// FIX: This is the fix for #2649, but it will need to be modified once we
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// decide to properly handle allenes
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dblBond->setBondDir(Bond::EITHERDOUBLE);
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}
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return;
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}
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Bond *bond2 = nullptr, *obond2 = nullptr;
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controllingBondFromAtom(mol, needsDir, singleBondCounts, dblBond,
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dblBond->getEndAtom(), bond2, obond2,
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squiggleBondSeen, doubleBondSeen);
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// Don't do any direction setting if we've seen a squiggle bond, but do mark
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// the double bond as a crossed bond and return
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if (!bond2 || squiggleBondSeen || doubleBondSeen) {
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if (!doubleBondSeen) {
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// FIX: This is the fix for #2649, but it will need to be modified once we
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// decide to properly handle allenes
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dblBond->setBondDir(Bond::EITHERDOUBLE);
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}
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return;
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}
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CHECK_INVARIANT(bond1 && bond2, "no bonds found");
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bool sameTorsionDir = false;
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if (conf) {
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RDGeom::Point3D beginP = conf->getAtomPos(dblBond->getBeginAtomIdx());
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RDGeom::Point3D endP = conf->getAtomPos(dblBond->getEndAtomIdx());
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RDGeom::Point3D bond1P =
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conf->getAtomPos(bond1->getOtherAtomIdx(dblBond->getBeginAtomIdx()));
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RDGeom::Point3D bond2P =
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conf->getAtomPos(bond2->getOtherAtomIdx(dblBond->getEndAtomIdx()));
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// check for a linear arrangement of atoms on either end:
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bool linear = false;
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RDGeom::Point3D p1;
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RDGeom::Point3D p2;
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p1 = bond1P - beginP;
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p2 = endP - beginP;
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if (isLinearArrangement(p1, p2)) {
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if (!obond1) {
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linear = true;
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} else {
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// one of the bonds was linear; what about the other one?
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Bond *tBond = bond1;
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bond1 = obond1;
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obond1 = tBond;
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bond1P = conf->getAtomPos(
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bond1->getOtherAtomIdx(dblBond->getBeginAtomIdx()));
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p1 = bond1P - beginP;
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if (isLinearArrangement(p1, p2)) {
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linear = true;
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}
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}
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}
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if (!linear) {
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p1 = bond2P - endP;
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p2 = beginP - endP;
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if (isLinearArrangement(p1, p2)) {
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if (!obond2) {
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linear = true;
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} else {
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Bond *tBond = bond2;
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bond2 = obond2;
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obond2 = tBond;
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bond2P = conf->getAtomPos(
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bond2->getOtherAtomIdx(dblBond->getEndAtomIdx()));
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p1 = bond2P - beginP;
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if (isLinearArrangement(p1, p2)) {
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linear = true;
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}
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}
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}
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}
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if (linear) {
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dblBond->setBondDir(Bond::EITHERDOUBLE);
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return;
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}
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double ang = RDGeom::computeDihedralAngle(bond1P, beginP, endP, bond2P);
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sameTorsionDir = ang >= M_PI / 2;
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// std::cerr << " angle: " << ang << " sameTorsionDir: " << sameTorsionDir
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// << "\n";
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} else {
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if (dblBond->getStereo() == Bond::STEREOCIS ||
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dblBond->getStereo() == Bond::STEREOZ) {
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sameTorsionDir = false;
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} else if (dblBond->getStereo() == Bond::STEREOTRANS ||
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dblBond->getStereo() == Bond::STEREOE) {
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sameTorsionDir = true;
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} else {
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return;
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}
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// if bond1 or bond2 are not to the stereo-controlling atoms, flip
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// our expections of the torsion dir
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int bond1AtomIdx = bond1->getOtherAtomIdx(dblBond->getBeginAtomIdx());
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if (bond1AtomIdx != dblBond->getStereoAtoms()[0] &&
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bond1AtomIdx != dblBond->getStereoAtoms()[1]) {
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sameTorsionDir = !sameTorsionDir;
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}
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int bond2AtomIdx = bond2->getOtherAtomIdx(dblBond->getEndAtomIdx());
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if (bond2AtomIdx != dblBond->getStereoAtoms()[0] &&
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bond2AtomIdx != dblBond->getStereoAtoms()[1]) {
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sameTorsionDir = !sameTorsionDir;
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}
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}
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/*
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Time for some clarificatory text, because this gets really
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confusing really fast.
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The dihedral angle analysis above is based on viewing things
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with an atom order as follows:
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1
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\
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2 = 3
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\
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4
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so dihedrals > 90 correspond to sameDir=true
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however, the stereochemistry representation is
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based on something more like this:
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2
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\
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1 = 3
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\
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4
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(i.e. we consider the direction-setting single bonds to be
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starting at the double-bonded atom)
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*/
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bool reverseBondDir = sameTorsionDir;
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Atom *atom1 = dblBond->getBeginAtom(), *atom2 = dblBond->getEndAtom();
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if (needsDir[bond1->getIdx()]) {
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for (auto bidx : singleBondNbrs[bond1->getIdx()]) {
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// std::cerr << " neighbor from: " << bond1->getIdx() << " " << bidx
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// << ": " << needsDir[bidx] << std::endl;
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if (needsDir[bidx]) {
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followupBonds.push_back(mol.getBondWithIdx(bidx));
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}
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}
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}
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if (needsDir[bond2->getIdx()]) {
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for (auto bidx : singleBondNbrs[bond2->getIdx()]) {
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// std::cerr << " neighbor from: " << bond2->getIdx() << " " << bidx
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// << ": " << needsDir[bidx] << std::endl;
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if (needsDir[bidx]) {
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followupBonds.push_back(mol.getBondWithIdx(bidx));
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}
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}
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}
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if (!needsDir[bond1->getIdx()]) {
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if (!needsDir[bond2->getIdx()]) {
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// check that we agree
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} else {
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if (bond1->getBeginAtom() != atom1) {
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reverseBondDir = !reverseBondDir;
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}
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setBondDirRelativeToAtom(bond2, atom2, bond1->getBondDir(),
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reverseBondDir, needsDir);
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}
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} else if (!needsDir[bond2->getIdx()]) {
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if (bond2->getBeginAtom() != atom2) {
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reverseBondDir = !reverseBondDir;
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}
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setBondDirRelativeToAtom(bond1, atom1, bond2->getBondDir(), reverseBondDir,
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needsDir);
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} else {
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setBondDirRelativeToAtom(bond1, atom1, Bond::ENDDOWNRIGHT, false, needsDir);
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setBondDirRelativeToAtom(bond2, atom2, Bond::ENDDOWNRIGHT, reverseBondDir,
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needsDir);
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}
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needsDir[bond1->getIdx()] = 0;
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needsDir[bond2->getIdx()] = 0;
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if (obond1 && needsDir[obond1->getIdx()]) {
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setBondDirRelativeToAtom(obond1, atom1, bond1->getBondDir(),
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bond1->getBeginAtom() == atom1, needsDir);
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needsDir[obond1->getIdx()] = 0;
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}
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if (obond2 && needsDir[obond2->getIdx()]) {
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setBondDirRelativeToAtom(obond2, atom2, bond2->getBondDir(),
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bond2->getBeginAtom() == atom2, needsDir);
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needsDir[obond2->getIdx()] = 0;
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}
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#if 0
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std::cerr << " 1:" << bond1->getIdx() << " ";
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if (obond1)
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std::cerr << obond1->getIdx() << std::endl;
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else
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std::cerr << "N/A" << std::endl;
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std::cerr << " 2:" << bond2->getIdx() << " ";
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if (obond2)
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std::cerr << obond2->getIdx() << std::endl;
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else
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std::cerr << "N/A" << std::endl;
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std::cerr << "**********************\n";
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std::cerr << "**********************\n";
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std::cerr << "**********************\n";
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#endif
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for (Bond *oDblBond : followupBonds) {
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// std::cerr << "FOLLOWUP: " << oDblBond->getIdx() << " "
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// << needsDir[oDblBond->getIdx()] << std::endl;
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updateDoubleBondNeighbors(mol, oDblBond, conf, needsDir, singleBondCounts,
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singleBondNbrs);
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}
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}
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bool isBondCandidateForStereo(const Bond *bond) {
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PRECONDITION(bond, "no bond");
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return bond->getBondType() == Bond::DOUBLE &&
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bond->getStereo() != Bond::STEREOANY &&
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bond->getBondDir() != Bond::EITHERDOUBLE &&
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bond->getBeginAtom()->getDegree() > 1u &&
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bond->getEndAtom()->getDegree() > 1u &&
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shouldDetectDoubleBondStereo(bond);
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}
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const Atom *findHighestCIPNeighbor(const Atom *atom, const Atom *skipAtom) {
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PRECONDITION(atom, "bad atom");
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unsigned bestCipRank = 0;
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const Atom *bestCipRankedAtom = nullptr;
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const auto &mol = atom->getOwningMol();
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for (const auto neighbor : mol.atomNeighbors(atom)) {
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if (neighbor == skipAtom) {
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continue;
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}
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unsigned cip = 0;
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if (!neighbor->getPropIfPresent(common_properties::_CIPRank, cip)) {
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// If at least one of the atoms doesn't have a CIP rank, the highest rank
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// does not make sense, so return a nullptr.
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return nullptr;
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} else if (cip > bestCipRank || bestCipRankedAtom == nullptr) {
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bestCipRank = cip;
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bestCipRankedAtom = neighbor;
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} else if (cip == bestCipRank) {
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// This also doesn't make sense if there is a tie (if that's possible).
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// We still keep the best CIP rank in case something better comes around
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// (also not sure if that's possible).
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BOOST_LOG(rdWarningLog)
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<< "Warning: duplicate CIP ranks found in findHighestCIPNeighbor()"
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<< std::endl;
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bestCipRankedAtom = nullptr;
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}
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}
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return bestCipRankedAtom;
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}
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} // namespace
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namespace Chirality {
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|
std::optional<Atom::ChiralType> atomChiralTypeFromBondDirPseudo3D(
|
|
const ROMol &mol, const Bond *bond, const Conformer *conf,
|
|
double pseudo3DOffset = 0.1, double volumeTolerance = 0.01) {
|
|
PRECONDITION(bond, "no bond");
|
|
PRECONDITION(conf, "no conformer");
|
|
auto bondDir = bond->getBondDir();
|
|
PRECONDITION(bondDir == Bond::BEGINWEDGE || bondDir == Bond::BEGINDASH,
|
|
"bad bond direction");
|
|
constexpr double zeroTol = 1e-4;
|
|
|
|
// NOTE that according to the CT file spec, wedging assigns chirality
|
|
// to the atom at the point of the wedge, (atom 1 in the bond).
|
|
const auto atom = bond->getBeginAtom();
|
|
PRECONDITION(atom, "no atom");
|
|
|
|
// we can't do anything with atoms that have more than 4 neighbors:
|
|
if (atom->getDegree() > 4) {
|
|
return Atom::CHI_UNSPECIFIED;
|
|
}
|
|
const auto bondAtom = bond->getEndAtom();
|
|
|
|
Atom::ChiralType res = Atom::CHI_UNSPECIFIED;
|
|
|
|
auto centerLoc = conf->getAtomPos(atom->getIdx());
|
|
centerLoc.z = 0.0;
|
|
auto refPt = conf->getAtomPos(bondAtom->getIdx());
|
|
refPt.z =
|
|
bondDir == Bond::BondDir::BEGINWEDGE ? pseudo3DOffset : -pseudo3DOffset;
|
|
|
|
//----------------------------------------------------------
|
|
//
|
|
// collect coordinates and indices of neighbors and track whether or
|
|
// not there's an H neighbor and if all bonds are single
|
|
//
|
|
//----------------------------------------------------------
|
|
bool hSeen = false;
|
|
|
|
INT_LIST neighborBondIndices;
|
|
neighborBondIndices.push_back(bond->getIdx());
|
|
if (is_regular_h(*bondAtom)) {
|
|
hSeen = true;
|
|
}
|
|
|
|
unsigned int refIdx = mol.getNumBonds() + 1;
|
|
std::vector<RDGeom::Point3D> bondVects;
|
|
bool allSingle = true;
|
|
unsigned int nbrIdx = 0;
|
|
for (const auto nbrBond : mol.atomBonds(atom)) {
|
|
const auto oAtom = nbrBond->getOtherAtom(atom);
|
|
auto tmpPt = conf->getAtomPos(oAtom->getIdx());
|
|
if (nbrBond == bond) {
|
|
refIdx = nbrIdx;
|
|
tmpPt = refPt;
|
|
} else {
|
|
// theoretically we could confirm that this is a single bond,
|
|
// but it's not impossible that at some point in the future we
|
|
// could allow wedged multiple bonds for things like atropisomers
|
|
if (nbrBond->getBeginAtomIdx() == atom->getIdx() &&
|
|
nbrBond->getBondDir() == Bond::BondDir::BEGINWEDGE) {
|
|
tmpPt.z = pseudo3DOffset;
|
|
} else if (nbrBond->getBeginAtomIdx() == atom->getIdx() &&
|
|
nbrBond->getBondDir() == Bond::BondDir::BEGINDASH) {
|
|
tmpPt.z = -pseudo3DOffset;
|
|
} else {
|
|
tmpPt.z = 0;
|
|
}
|
|
}
|
|
++nbrIdx;
|
|
if (nbrBond->getBondType() != Bond::SINGLE) {
|
|
allSingle = false;
|
|
}
|
|
bondVects.push_back(centerLoc.directionVector(tmpPt));
|
|
if (is_regular_h(*oAtom)) {
|
|
hSeen = true;
|
|
}
|
|
neighborBondIndices.push_back(nbrBond->getIdx());
|
|
}
|
|
CHECK_INVARIANT(refIdx < mol.getNumBonds(),
|
|
"could not find reference bond in neighbors");
|
|
|
|
auto nNbrs = bondVects.size();
|
|
|
|
//----------------------------------------------------------
|
|
//
|
|
// Return now if there aren't at least 3 non-H bonds to the atom.
|
|
// (we can implicitly add a single H to 3 coordinate atoms, but
|
|
// we're horked otherwise).
|
|
//
|
|
//----------------------------------------------------------
|
|
if (nNbrs < 3 || nNbrs > 4 || (hSeen && nNbrs < 4)) {
|
|
return std::nullopt;
|
|
}
|
|
|
|
//----------------------------------------------------------
|
|
//
|
|
// Continue if there are all single bonds or if we're considering
|
|
// 4-coordinate P or S
|
|
//
|
|
//----------------------------------------------------------
|
|
if (allSingle || atom->getAtomicNum() == 15 || atom->getAtomicNum() == 16) {
|
|
double vol;
|
|
unsigned int order[4] = {0, 1, 2, 3};
|
|
double prefactor = 1;
|
|
if (refIdx != 0) {
|
|
// bring the wedged bond to the front so that we always consider it
|
|
std::swap(order[0], order[refIdx]);
|
|
prefactor *= -1;
|
|
}
|
|
|
|
// three-coordinate special cases where chirality cannot be determined
|
|
//
|
|
// Case 1:
|
|
// this one is never allowed with different directions for the bonds to 1
|
|
// and 2
|
|
// 0 2
|
|
// \ /
|
|
// C
|
|
// *
|
|
// 1
|
|
// This is ST-1.2.10 in the IUPAC guidelines
|
|
//
|
|
// Case 2: all bonds are wedged in the same direction
|
|
|
|
if (nNbrs == 3) {
|
|
bool conflict = false;
|
|
if (bondVects[order[1]].z * bondVects[order[0]].z < -zeroTol &&
|
|
fabs(bondVects[order[2]].z) < zeroTol) {
|
|
conflict = bondVects[order[2]].crossProduct(bondVects[order[0]]).z *
|
|
bondVects[order[2]].crossProduct(bondVects[order[1]]).z <
|
|
-1e-4;
|
|
} else if (bondVects[order[2]].z * bondVects[order[0]].z < -zeroTol &&
|
|
fabs(bondVects[order[1]].z) < zeroTol) {
|
|
conflict = bondVects[order[1]].crossProduct(bondVects[order[0]]).z *
|
|
bondVects[order[1]].crossProduct(bondVects[order[2]]).z <
|
|
-zeroTol;
|
|
}
|
|
if (conflict) {
|
|
BOOST_LOG(rdWarningLog)
|
|
<< "Warning: conflicting stereochemistry at atom "
|
|
<< bond->getBeginAtomIdx() << " ignored"
|
|
<< " by rule 1a." << std::endl;
|
|
return std::nullopt;
|
|
}
|
|
}
|
|
|
|
const auto crossp1 = bondVects[order[1]].crossProduct(bondVects[order[2]]);
|
|
// catch linear arrangements
|
|
if (crossp1.lengthSq() < zeroTol) {
|
|
// nothing we can do if there are only three neighbors
|
|
if (nNbrs == 3) {
|
|
BOOST_LOG(rdWarningLog)
|
|
<< "Warning: ambiguous stereochemistry - linear bond arrangement - at atom "
|
|
<< bond->getBeginAtomIdx() << " ignored" << std::endl;
|
|
return std::nullopt;
|
|
}
|
|
// if the bond on the other side is flat, wedge it the same way as bond 0:
|
|
if (fabs(bondVects[order[3]].z) < zeroTol) {
|
|
bondVects[order[3]].z = bondVects[order[0]].z;
|
|
} else if (bondVects[order[3]].z * bondVects[order[0]].z < -zeroTol) {
|
|
// it points opposite to bond 0... this is ambiguous (technically it's
|
|
// square planar)
|
|
BOOST_LOG(rdWarningLog)
|
|
<< "Warning: ambiguous stereochemistry - square planar wedging - at atom "
|
|
<< bond->getBeginAtomIdx() << " ignored" << std::endl;
|
|
return std::nullopt;
|
|
}
|
|
}
|
|
vol = crossp1.dotProduct(bondVects[order[0]]);
|
|
if (nNbrs == 4) {
|
|
const auto dotp1 = bondVects[order[1]].dotProduct(bondVects[order[2]]);
|
|
const auto crossp2 =
|
|
bondVects[order[1]].crossProduct(bondVects[order[3]]);
|
|
const auto dotp2 = bondVects[order[1]].dotProduct(bondVects[order[3]]);
|
|
auto vol2 = crossp2.dotProduct(bondVects[order[0]]);
|
|
// std::cerr << bondVects[0] << std::endl;
|
|
// std::cerr << bondVects[1] << std::endl;
|
|
// std::cerr << bondVects[2] << std::endl;
|
|
// std::cerr << bondVects[3] << std::endl;
|
|
// std::cerr << "------------" << std::endl;
|
|
// std::cerr << crossp1 << " " << dotp1 << std::endl;
|
|
// std::cerr << crossp2 << " " << dotp2 << std::endl;
|
|
// std::cerr << " !!! " << vol << " " << vol2 << std::endl;
|
|
if (fabs(vol) < zeroTol) {
|
|
if (fabs(vol2) < zeroTol) {
|
|
BOOST_LOG(rdWarningLog)
|
|
<< "Warning: ambiguous stereochemistry - no chiral volume - at atom "
|
|
<< bond->getBeginAtomIdx() << " ignored" << std::endl;
|
|
return std::nullopt;
|
|
}
|
|
vol = vol2;
|
|
prefactor *= -1;
|
|
} else if (vol * vol2 > 0 && dotp1 < dotp2) {
|
|
prefactor *= -1;
|
|
}
|
|
}
|
|
vol *= prefactor;
|
|
if (vol > volumeTolerance) {
|
|
res = Atom::ChiralType::CHI_TETRAHEDRAL_CCW;
|
|
} else if (vol < volumeTolerance) {
|
|
res = Atom::ChiralType::CHI_TETRAHEDRAL_CW;
|
|
} else {
|
|
return std::nullopt;
|
|
}
|
|
}
|
|
|
|
return res;
|
|
}
|
|
|
|
#ifdef _WIN32
|
|
int setenv(const char *name, const char *value, int) {
|
|
return _putenv_s(name, value);
|
|
}
|
|
#endif
|
|
|
|
void setAllowNontetrahedralChirality(bool val) {
|
|
if (val) {
|
|
setenv(nonTetrahedralStereoEnvVar, "1", 1);
|
|
} else {
|
|
setenv(nonTetrahedralStereoEnvVar, "0", 1);
|
|
}
|
|
}
|
|
bool getAllowNontetrahedralChirality() {
|
|
return getValFromEnvironment(nonTetrahedralStereoEnvVar,
|
|
nonTetrahedralStereoDefaultVal);
|
|
}
|
|
|
|
void setUseLegacyStereoPerception(bool val) {
|
|
if (val) {
|
|
setenv(useLegacyStereoEnvVar, "1", 1);
|
|
} else {
|
|
setenv(useLegacyStereoEnvVar, "0", 1);
|
|
}
|
|
}
|
|
bool getUseLegacyStereoPerception() {
|
|
return getValFromEnvironment(useLegacyStereoEnvVar,
|
|
useLegacyStereoDefaultVal);
|
|
}
|
|
|
|
namespace detail {
|
|
bool bondAffectsAtomChirality(const Bond *bond, const Atom *atom) {
|
|
// FIX consider how to handle organometallics
|
|
PRECONDITION(bond, "bad bond pointer");
|
|
PRECONDITION(atom, "bad atom pointer");
|
|
if (bond->getBondType() == Bond::BondType::UNSPECIFIED ||
|
|
bond->getBondType() == Bond::BondType::ZERO ||
|
|
(bond->getBondType() == Bond::BondType::DATIVE &&
|
|
bond->getBeginAtomIdx() == atom->getIdx())) {
|
|
return false;
|
|
}
|
|
return true;
|
|
}
|
|
unsigned int getAtomNonzeroDegree(const Atom *atom) {
|
|
PRECONDITION(atom, "bad pointer");
|
|
PRECONDITION(atom->hasOwningMol(), "no owning molecule");
|
|
unsigned int res = 0;
|
|
for (auto bond : atom->getOwningMol().atomBonds(atom)) {
|
|
if (!bondAffectsAtomChirality(bond, atom)) {
|
|
continue;
|
|
}
|
|
++res;
|
|
}
|
|
return res;
|
|
}
|
|
|
|
bool has_protium_neighbor(const ROMol &mol, const Atom *atom) {
|
|
for (const auto nbr : mol.atomNeighbors(atom)) {
|
|
if (is_regular_h(*nbr)) {
|
|
return true;
|
|
}
|
|
}
|
|
return false;
|
|
}
|
|
|
|
} // namespace detail
|
|
|
|
typedef std::pair<int, int> INT_PAIR;
|
|
typedef std::vector<INT_PAIR> INT_PAIR_VECT;
|
|
typedef std::vector<INT_PAIR>::iterator INT_PAIR_VECT_I;
|
|
typedef std::vector<INT_PAIR>::const_iterator INT_PAIR_VECT_CI;
|
|
|
|
typedef INT_VECT CIP_ENTRY;
|
|
typedef std::vector<CIP_ENTRY> CIP_ENTRY_VECT;
|
|
|
|
template <typename T>
|
|
void debugVect(const std::vector<T> arg) {
|
|
typename std::vector<T>::const_iterator viIt;
|
|
std::stringstream outS;
|
|
for (viIt = arg.begin(); viIt != arg.end(); viIt++) {
|
|
outS << *viIt << " ";
|
|
}
|
|
BOOST_LOG(rdDebugLog) << outS.str() << std::endl;
|
|
}
|
|
|
|
// --------------------------------------------------
|
|
//
|
|
// Calculates chiral invariants for the atoms of a molecule
|
|
// These are based on Labute's proposal in:
|
|
// "An Efficient Algorithm for the Determination of Topological
|
|
// RS Chirality" Journal of the CCG (1996)
|
|
//
|
|
// --------------------------------------------------
|
|
void buildCIPInvariants(const ROMol &mol, DOUBLE_VECT &res) {
|
|
PRECONDITION(res.size() >= mol.getNumAtoms(), "res vect too small");
|
|
int atsSoFar = 0;
|
|
//
|
|
// NOTE:
|
|
// If you make modifications to this, keep in mind that it is
|
|
// essential that the initial comparison of ranks behave properly.
|
|
// So, though it seems like it would makes sense to include
|
|
// information about the number of Hs (or charge, etc) in the CIP
|
|
// invariants, this will result in bad rankings. For example, in
|
|
// this molecule: OC[C@H](C)O, including the number of Hs would
|
|
// cause the methyl group (atom 3) to be ranked higher than the CH2
|
|
// connected to O (atom 1). This is totally wrong.
|
|
//
|
|
// We also don't include any pre-existing stereochemistry information.
|
|
// Though R and S assignments do factor in to the priorities of atoms,
|
|
// we're starting here from scratch and we'll let the R and S stuff
|
|
// be taken into account during the iterations.
|
|
//
|
|
for (const auto atom : mol.atoms()) {
|
|
const unsigned short nMassBits = 10;
|
|
const unsigned short maxMass = 1 << nMassBits;
|
|
unsigned long invariant = 0;
|
|
int num = atom->getAtomicNum() % 128;
|
|
// get an int with the deviation in the mass from the default:
|
|
int mass = 0;
|
|
if (atom->getIsotope()) {
|
|
mass =
|
|
atom->getIsotope() -
|
|
PeriodicTable::getTable()->getMostCommonIsotope(atom->getAtomicNum());
|
|
if (mass >= 0) {
|
|
mass += 1;
|
|
}
|
|
}
|
|
mass += maxMass / 2;
|
|
if (mass < 0) {
|
|
mass = 0;
|
|
} else {
|
|
mass = mass % maxMass;
|
|
}
|
|
|
|
#if 0
|
|
// NOTE: the inclusion of hybridization in the invariant (as
|
|
// suggested in the original paper), leads to the situation
|
|
// that
|
|
// C[C@@](O)(C=C)C(C)CC
|
|
// and
|
|
// C[C@@](O)(C=C)C(C)CO
|
|
// are assigned S chirality even though the rest of the world
|
|
// seems to agree that they ought to be R (atom 3, sp2, is ranked
|
|
// higher than atom 5, sp3, no matter what their environments)
|
|
int hyb=0;
|
|
switch(atom->getHybridization()) {
|
|
case Atom::SP: hyb=6;break;
|
|
case Atom::SP2: hyb=5;break;
|
|
case Atom::SP3: hyb=1;break;
|
|
case Atom::SP3D: hyb=3;break;
|
|
case Atom::SP3D2: hyb=2;break;
|
|
default: break;
|
|
}
|
|
#endif
|
|
|
|
invariant = num; // 7 bits here
|
|
invariant = (invariant << nMassBits) | mass;
|
|
|
|
int mapnum = -1;
|
|
atom->getPropIfPresent(common_properties::molAtomMapNumber, mapnum);
|
|
mapnum = (mapnum + 1) % 1024; // increment to allow map numbers of zero
|
|
// (though that would be stupid)
|
|
invariant = (invariant << 10) | mapnum;
|
|
|
|
res[atsSoFar++] = invariant;
|
|
}
|
|
}
|
|
|
|
void iterateCIPRanks(const ROMol &mol, const DOUBLE_VECT &invars,
|
|
UINT_VECT &ranks, bool seedWithInvars) {
|
|
PRECONDITION(invars.size() == mol.getNumAtoms(), "bad invars size");
|
|
PRECONDITION(ranks.size() >= mol.getNumAtoms(), "bad ranks size");
|
|
|
|
unsigned int numAtoms = mol.getNumAtoms();
|
|
CIP_ENTRY_VECT cipEntries(numAtoms);
|
|
for (auto &vec : cipEntries) {
|
|
vec.reserve(16);
|
|
}
|
|
#ifdef VERBOSE_CANON
|
|
BOOST_LOG(rdDebugLog) << "invariants:" << std::endl;
|
|
for (unsigned int i = 0; i < numAtoms; i++) {
|
|
BOOST_LOG(rdDebugLog) << i << ": " << invars[i] << std::endl;
|
|
}
|
|
#endif
|
|
|
|
// rank those:
|
|
Rankers::rankVect(invars, ranks);
|
|
#ifdef VERBOSE_CANON
|
|
BOOST_LOG(rdDebugLog) << "initial ranks:" << std::endl;
|
|
for (unsigned int i = 0; i < numAtoms; ++i) {
|
|
BOOST_LOG(rdDebugLog) << i << ": " << ranks[i] << std::endl;
|
|
}
|
|
#endif
|
|
// Start each atom's rank vector with its atomic number:
|
|
// Note: in general one should avoid the temptation to
|
|
// use invariants here, those lead to incorrect answers
|
|
for (unsigned int i = 0; i < numAtoms; i++) {
|
|
if (seedWithInvars) {
|
|
cipEntries[i].push_back(static_cast<int>(invars[i]));
|
|
} else {
|
|
cipEntries[i].push_back(mol[i]->getAtomicNum());
|
|
cipEntries[i].push_back(static_cast<int>(ranks[i]));
|
|
}
|
|
}
|
|
|
|
// Loop until either:
|
|
// 1) all classes are uniquified
|
|
// 2) the number of ranks doesn't change from one iteration to
|
|
// the next
|
|
// 3) we've gone through maxIts times
|
|
// maxIts is calculated by dividing the number of atoms
|
|
// by 2. That's a pessimal version of the
|
|
// maximum number of steps required for two atoms to
|
|
// "feel" each other (each influences one additional
|
|
// neighbor shell per iteration).
|
|
unsigned int maxIts = numAtoms / 2 + 1;
|
|
unsigned int numIts = 0;
|
|
int lastNumRanks = -1;
|
|
unsigned int numRanks = *std::max_element(ranks.begin(), ranks.end()) + 1;
|
|
std::vector<unsigned int> counts(ranks.size());
|
|
std::vector<unsigned int> updatedNbrIdxs;
|
|
updatedNbrIdxs.reserve(8);
|
|
while (numRanks < numAtoms && numIts < maxIts &&
|
|
(lastNumRanks < 0 ||
|
|
static_cast<unsigned int>(lastNumRanks) < numRanks)) {
|
|
unsigned int longestEntry = 0;
|
|
// ----------------------------------------------------
|
|
//
|
|
// for each atom, get a sorted list of its neighbors' ranks:
|
|
//
|
|
for (unsigned int index = 0; index < numAtoms; ++index) {
|
|
// Note: counts is cleaned up when we drain into cipEntries.
|
|
updatedNbrIdxs.clear();
|
|
|
|
// start by pushing on our neighbors' ranks:
|
|
for (const auto bond : mol.atomBonds(mol[index])) {
|
|
unsigned int nbrIdx = bond->getOtherAtomIdx(index);
|
|
updatedNbrIdxs.push_back(nbrIdx);
|
|
|
|
// put the neighbor in 2N times where N is the bond order as a double.
|
|
// this is to treat aromatic linkages on fair footing. i.e. at least in
|
|
// the first iteration --c(:c):c and --C(=C)-C should look the same.
|
|
// this was part of issue 3009911
|
|
|
|
// a special case for chiral phosphorus compounds
|
|
// (this was leading to incorrect assignment of R/S labels ):
|
|
bool isChiralPhosphorusSpecialCase = false;
|
|
if (bond->getBondType() == Bond::DOUBLE) {
|
|
const Atom *nbr = mol[nbrIdx];
|
|
if (nbr->getAtomicNum() == 15) {
|
|
unsigned int nbrDeg = nbr->getDegree();
|
|
isChiralPhosphorusSpecialCase = nbrDeg == 3 || nbrDeg == 4;
|
|
}
|
|
};
|
|
|
|
// general justification of this is:
|
|
// Paragraph 2.2. in the 1966 article is "Valence-Bond Conventions:
|
|
// Multiple-Bond Unsaturation and Aromaticity". It contains several
|
|
// conventions of which convention (b) is the one applying here:
|
|
// "(b) Contributions by d orbitals to bonds of quadriligant atoms are
|
|
// neglected."
|
|
// FIX: this applies to more than just P
|
|
if (isChiralPhosphorusSpecialCase) {
|
|
counts[nbrIdx] += 1;
|
|
} else {
|
|
counts[nbrIdx] += getTwiceBondType(*bond);
|
|
}
|
|
}
|
|
|
|
// For each of our neighbors' ranks weighted by bond type, copy it N times
|
|
// to our cipEntry in reverse rank order, where N is the weight.
|
|
if (updatedNbrIdxs.size() > 1) { // compare vs 1 for performance.
|
|
std::sort(std::begin(updatedNbrIdxs), std::end(updatedNbrIdxs),
|
|
[&ranks](unsigned int idx1, unsigned int idx2) {
|
|
return ranks[idx1] > ranks[idx2];
|
|
});
|
|
}
|
|
auto &cipEntry = cipEntries[index];
|
|
for (auto nbrIdx : updatedNbrIdxs) {
|
|
unsigned int count = counts[nbrIdx];
|
|
cipEntry.insert(cipEntry.end(), count, ranks[nbrIdx] + 1);
|
|
counts[nbrIdx] = 0;
|
|
}
|
|
// add a zero for each coordinated H as long as we're not a query atom
|
|
if (!mol[index]->hasQuery()) {
|
|
cipEntry.insert(cipEntry.end(), mol[index]->getTotalNumHs(), 0);
|
|
}
|
|
|
|
if (cipEntry.size() > longestEntry) {
|
|
longestEntry = rdcast<unsigned int>(cipEntry.size());
|
|
}
|
|
}
|
|
// ----------------------------------------------------
|
|
//
|
|
// pad the entries so that we compare rounds to themselves:
|
|
//
|
|
for (unsigned int index = 0; index < numAtoms; ++index) {
|
|
auto sz = rdcast<unsigned int>(cipEntries[index].size());
|
|
if (sz < longestEntry) {
|
|
cipEntries[index].insert(cipEntries[index].end(), longestEntry - sz,
|
|
-1);
|
|
}
|
|
}
|
|
// ----------------------------------------------------
|
|
//
|
|
// sort the new ranks and update the list of active indices:
|
|
//
|
|
lastNumRanks = numRanks;
|
|
|
|
Rankers::rankVect(cipEntries, ranks);
|
|
numRanks = *std::max_element(ranks.begin(), ranks.end()) + 1;
|
|
|
|
// now truncate each vector and stick the rank at the end
|
|
if (static_cast<unsigned int>(lastNumRanks) != numRanks) {
|
|
for (unsigned int i = 0; i < numAtoms; ++i) {
|
|
cipEntries[i][numIts + 1] = ranks[i];
|
|
cipEntries[i].erase(cipEntries[i].begin() + numIts + 2,
|
|
cipEntries[i].end());
|
|
}
|
|
}
|
|
|
|
++numIts;
|
|
#ifdef VERBOSE_CANON
|
|
BOOST_LOG(rdDebugLog) << "strings and ranks:" << std::endl;
|
|
for (unsigned int i = 0; i < numAtoms; i++) {
|
|
BOOST_LOG(rdDebugLog) << i << ": " << ranks[i] << " > ";
|
|
debugVect(cipEntries[i]);
|
|
}
|
|
#endif
|
|
}
|
|
}
|
|
// Figure out the CIP ranks for the atoms of a molecule
|
|
void assignAtomCIPRanks(const ROMol &mol, UINT_VECT &ranks) {
|
|
PRECONDITION((!ranks.size() || ranks.size() >= mol.getNumAtoms()),
|
|
"bad ranks size");
|
|
if (!ranks.size()) {
|
|
ranks.resize(mol.getNumAtoms());
|
|
}
|
|
unsigned int numAtoms = mol.getNumAtoms();
|
|
#ifndef USE_NEW_STEREOCHEMISTRY
|
|
// get the initial invariants:
|
|
DOUBLE_VECT invars(numAtoms, 0);
|
|
buildCIPInvariants(mol, invars);
|
|
iterateCIPRanks(mol, invars, ranks, false);
|
|
#else
|
|
Canon::chiralRankMolAtoms(mol, ranks);
|
|
#endif
|
|
|
|
// copy the ranks onto the atoms:
|
|
for (unsigned int i = 0; i < numAtoms; ++i) {
|
|
mol[i]->setProp(common_properties::_CIPRank, ranks[i], 1);
|
|
}
|
|
}
|
|
|
|
// construct a vector with <atomIdx,direction> pairs for
|
|
// neighbors of a given atom. This list will only be
|
|
// non-empty if at least one of the bonds has its direction
|
|
// set.
|
|
void findAtomNeighborDirHelper(const ROMol &mol, const Atom *atom,
|
|
const Bond *refBond, UINT_VECT &ranks,
|
|
INT_PAIR_VECT &neighbors,
|
|
bool &hasExplicitUnknownStereo) {
|
|
PRECONDITION(atom, "bad atom");
|
|
PRECONDITION(refBond, "bad bond");
|
|
|
|
bool seenDir = false;
|
|
for (const auto bond : mol.atomBonds(atom)) {
|
|
// check whether this bond is explicitly set to have unknown stereo
|
|
if (!hasExplicitUnknownStereo) {
|
|
int explicit_unknown_stereo;
|
|
if (bond->getBondDir() == Bond::UNKNOWN // there's a squiggle bond
|
|
|| (bond->getPropIfPresent<int>(common_properties::_UnknownStereo,
|
|
explicit_unknown_stereo) &&
|
|
explicit_unknown_stereo)) {
|
|
hasExplicitUnknownStereo = true;
|
|
}
|
|
}
|
|
|
|
Bond::BondDir dir = bond->getBondDir();
|
|
if (bond->getIdx() != refBond->getIdx()) {
|
|
if (dir == Bond::ENDDOWNRIGHT || dir == Bond::ENDUPRIGHT) {
|
|
seenDir = true;
|
|
// If we're considering the bond "backwards", (i.e. from end
|
|
// to beginning, reverse the effective direction:
|
|
if (atom != bond->getBeginAtom()) {
|
|
if (dir == Bond::ENDDOWNRIGHT) {
|
|
dir = Bond::ENDUPRIGHT;
|
|
} else {
|
|
dir = Bond::ENDDOWNRIGHT;
|
|
}
|
|
}
|
|
}
|
|
Atom *nbrAtom = bond->getOtherAtom(atom);
|
|
neighbors.push_back(std::make_pair(nbrAtom->getIdx(), dir));
|
|
}
|
|
}
|
|
if (!seenDir) {
|
|
neighbors.clear();
|
|
} else {
|
|
if (neighbors.size() == 2 &&
|
|
ranks[neighbors[0].first] == ranks[neighbors[1].first]) {
|
|
// the two substituents are identical, no stereochemistry here:
|
|
neighbors.clear();
|
|
} else {
|
|
// it's possible that direction was set only one of the bonds, set the
|
|
// other
|
|
// bond's direction to be reversed:
|
|
if (neighbors[0].second != Bond::ENDDOWNRIGHT &&
|
|
neighbors[0].second != Bond::ENDUPRIGHT) {
|
|
CHECK_INVARIANT(neighbors.size() > 1, "too few neighbors");
|
|
neighbors[0].second = neighbors[1].second == Bond::ENDDOWNRIGHT
|
|
? Bond::ENDUPRIGHT
|
|
: Bond::ENDDOWNRIGHT;
|
|
} else if (neighbors.size() > 1 &&
|
|
neighbors[1].second != Bond::ENDDOWNRIGHT &&
|
|
neighbors[1].second != Bond::ENDUPRIGHT) {
|
|
neighbors[1].second = neighbors[0].second == Bond::ENDDOWNRIGHT
|
|
? Bond::ENDUPRIGHT
|
|
: Bond::ENDDOWNRIGHT;
|
|
}
|
|
}
|
|
}
|
|
}
|
|
|
|
// find the neighbors for an atoms that are not connected by single bond that is
|
|
// not refBond
|
|
// if checkDir is true only neighbor atoms with bonds marked with a direction
|
|
// will be returned
|
|
void findAtomNeighborsHelper(const ROMol &mol, const Atom *atom,
|
|
const Bond *refBond, UINT_VECT &neighbors,
|
|
bool checkDir = false,
|
|
bool includeAromatic = false) {
|
|
PRECONDITION(atom, "bad atom");
|
|
PRECONDITION(refBond, "bad bond");
|
|
neighbors.clear();
|
|
for (const auto bond : mol.atomBonds(atom)) {
|
|
if (bond == refBond) {
|
|
continue;
|
|
}
|
|
Bond::BondDir dir = bond->getBondDir();
|
|
if (bond->getBondType() == Bond::SINGLE ||
|
|
(includeAromatic && bond->getBondType() == Bond::AROMATIC)) {
|
|
if (checkDir) {
|
|
if ((dir != Bond::ENDDOWNRIGHT) && (dir != Bond::ENDUPRIGHT)) {
|
|
continue;
|
|
}
|
|
}
|
|
Atom *nbrAtom = bond->getOtherAtom(atom);
|
|
neighbors.push_back(nbrAtom->getIdx());
|
|
}
|
|
}
|
|
}
|
|
|
|
// conditions for an atom to be a candidate for ring stereochem:
|
|
// 1) two non-ring neighbors that have different ranks
|
|
// 2) one non-ring neighbor and two ring neighbors (the ring neighbors will
|
|
// have the same rank)
|
|
// 3) four ring neighbors with three different ranks
|
|
// 4) three ring neighbors with two different ranks
|
|
// example for this last one: C[C@H]1CC2CCCC3CCCC(C1)[C@@H]23
|
|
// Note that N atoms are only candidates if they are in a 3-ring
|
|
bool atomIsCandidateForRingStereochem(const ROMol &mol, const Atom *atom) {
|
|
PRECONDITION(atom, "bad atom");
|
|
bool res = false;
|
|
std::set<unsigned int> nbrRanks;
|
|
if (!atom->getPropIfPresent(common_properties::_ringStereochemCand, res)) {
|
|
const RingInfo *ringInfo = mol.getRingInfo();
|
|
if (ringInfo->isInitialized() && ringInfo->numAtomRings(atom->getIdx())) {
|
|
// three-coordinate N additional requirements:
|
|
// in a ring of size 3 (from InChI)
|
|
// OR
|
|
// a bridgehead (RDKit extension)
|
|
if (atom->getAtomicNum() == 7 && atom->getDegree() == 3 &&
|
|
!ringInfo->isAtomInRingOfSize(atom->getIdx(), 3) &&
|
|
!queryIsAtomBridgehead(atom)) {
|
|
return false;
|
|
}
|
|
std::vector<const Atom *> nonRingNbrs;
|
|
std::vector<const Atom *> ringNbrs;
|
|
for (const auto bond : mol.atomBonds(atom)) {
|
|
if (!ringInfo->numBondRings(bond->getIdx())) {
|
|
nonRingNbrs.push_back(bond->getOtherAtom(atom));
|
|
} else {
|
|
const Atom *nbr = bond->getOtherAtom(atom);
|
|
ringNbrs.push_back(nbr);
|
|
unsigned int rnk = 0;
|
|
nbr->getPropIfPresent(common_properties::_CIPRank, rnk);
|
|
nbrRanks.insert(rnk);
|
|
}
|
|
}
|
|
unsigned int rank1 = 0, rank2 = 0;
|
|
switch (nonRingNbrs.size()) {
|
|
case 2:
|
|
if (nonRingNbrs[0]->getPropIfPresent(common_properties::_CIPRank,
|
|
rank1) &&
|
|
nonRingNbrs[1]->getPropIfPresent(common_properties::_CIPRank,
|
|
rank2)) {
|
|
res = rank1 != rank2;
|
|
}
|
|
break;
|
|
case 1:
|
|
if (ringNbrs.size() >= 2) {
|
|
res = true;
|
|
}
|
|
break;
|
|
case 0:
|
|
if (ringNbrs.size() == 4 && nbrRanks.size() == 3) {
|
|
res = true;
|
|
} else if (ringNbrs.size() == 3 && nbrRanks.size() == 2) {
|
|
res = true;
|
|
} else {
|
|
res = false;
|
|
}
|
|
break;
|
|
default:
|
|
res = false;
|
|
}
|
|
}
|
|
atom->setProp(common_properties::_ringStereochemCand, res, 1);
|
|
}
|
|
return res;
|
|
}
|
|
|
|
// finds all possible chiral special cases.
|
|
// at the moment this is just candidates for ring stereochemistry
|
|
void findChiralAtomSpecialCases(ROMol &mol,
|
|
boost::dynamic_bitset<> &possibleSpecialCases) {
|
|
PRECONDITION(possibleSpecialCases.size() >= mol.getNumAtoms(),
|
|
"bit vector too small");
|
|
possibleSpecialCases.reset();
|
|
if (!mol.getRingInfo()->isInitialized()) {
|
|
VECT_INT_VECT sssrs;
|
|
MolOps::symmetrizeSSSR(mol, sssrs);
|
|
}
|
|
boost::dynamic_bitset<> atomsSeen(mol.getNumAtoms());
|
|
boost::dynamic_bitset<> atomsUsed(mol.getNumAtoms());
|
|
boost::dynamic_bitset<> bondsSeen(mol.getNumBonds());
|
|
|
|
for (const auto atom : mol.atoms()) {
|
|
if (atomsSeen[atom->getIdx()]) {
|
|
continue;
|
|
}
|
|
if (atom->getChiralTag() == Atom::CHI_UNSPECIFIED ||
|
|
atom->hasProp(common_properties::_CIPCode) ||
|
|
!mol.getRingInfo()->numAtomRings(atom->getIdx()) ||
|
|
!atomIsCandidateForRingStereochem(mol, atom)) {
|
|
continue;
|
|
}
|
|
// do a BFS from this ring atom along ring bonds and find other
|
|
// stereochemistry candidates.
|
|
std::list<const Atom *> nextAtoms;
|
|
// start with finding viable neighbors
|
|
for (const auto bond : mol.atomBonds(atom)) {
|
|
unsigned int bidx = bond->getIdx();
|
|
if (!bondsSeen[bidx]) {
|
|
bondsSeen.set(bidx);
|
|
if (mol.getRingInfo()->numBondRings(bidx)) {
|
|
const Atom *oatom = bond->getOtherAtom(atom);
|
|
if (!atomsSeen[oatom->getIdx()]) {
|
|
nextAtoms.push_back(oatom);
|
|
atomsUsed.set(oatom->getIdx());
|
|
}
|
|
}
|
|
}
|
|
}
|
|
INT_VECT ringStereoAtoms(0);
|
|
if (!nextAtoms.empty()) {
|
|
atom->getPropIfPresent(common_properties::_ringStereoAtoms,
|
|
ringStereoAtoms);
|
|
}
|
|
|
|
while (!nextAtoms.empty()) {
|
|
const Atom *ratom = nextAtoms.front();
|
|
nextAtoms.pop_front();
|
|
atomsSeen.set(ratom->getIdx());
|
|
if (ratom->getChiralTag() != Atom::CHI_UNSPECIFIED &&
|
|
!ratom->hasProp(common_properties::_CIPCode) &&
|
|
atomIsCandidateForRingStereochem(mol, ratom)) {
|
|
int same = (ratom->getChiralTag() == atom->getChiralTag()) ? 1 : -1;
|
|
ringStereoAtoms.push_back(same * (ratom->getIdx() + 1));
|
|
INT_VECT oringatoms(0);
|
|
ratom->getPropIfPresent(common_properties::_ringStereoAtoms,
|
|
oringatoms);
|
|
oringatoms.push_back(same * (atom->getIdx() + 1));
|
|
ratom->setProp(common_properties::_ringStereoAtoms, oringatoms, true);
|
|
possibleSpecialCases.set(ratom->getIdx());
|
|
possibleSpecialCases.set(atom->getIdx());
|
|
}
|
|
// now push this atom's neighbors
|
|
for (const auto bond : mol.atomBonds(ratom)) {
|
|
unsigned int bidx = bond->getIdx();
|
|
if (!bondsSeen[bidx]) {
|
|
bondsSeen.set(bidx);
|
|
if (mol.getRingInfo()->numBondRings(bidx)) {
|
|
const Atom *oatom = bond->getOtherAtom(ratom);
|
|
if (!atomsSeen[oatom->getIdx()] && !atomsUsed[oatom->getIdx()]) {
|
|
nextAtoms.push_back(oatom);
|
|
atomsUsed.set(oatom->getIdx());
|
|
}
|
|
}
|
|
}
|
|
}
|
|
} // end of BFS
|
|
if (ringStereoAtoms.size() != 0) {
|
|
atom->setProp(common_properties::_ringStereoAtoms, ringStereoAtoms, true);
|
|
// because we're only going to hit each ring atom once, the first atom we
|
|
// encounter in a ring is going to end up with all the other atoms set as
|
|
// stereoAtoms, but each of them will only have the first atom present. We
|
|
// need to fix that. because the traverse from the first atom only
|
|
// followed ring bonds, these things are all by definition in one ring
|
|
// system. (Q: is this true if there's a spiro center in there?)
|
|
INT_VECT same(mol.getNumAtoms(), 0);
|
|
for (auto ringAtomEntry : ringStereoAtoms) {
|
|
int ringAtomIdx =
|
|
ringAtomEntry < 0 ? -ringAtomEntry - 1 : ringAtomEntry - 1;
|
|
same[ringAtomIdx] = ringAtomEntry;
|
|
}
|
|
for (INT_VECT_CI rae = ringStereoAtoms.begin();
|
|
rae != ringStereoAtoms.end(); ++rae) {
|
|
int ringAtomEntry = *rae;
|
|
int ringAtomIdx =
|
|
ringAtomEntry < 0 ? -ringAtomEntry - 1 : ringAtomEntry - 1;
|
|
INT_VECT lringatoms(0);
|
|
mol.getAtomWithIdx(ringAtomIdx)
|
|
->getPropIfPresent(common_properties::_ringStereoAtoms, lringatoms);
|
|
CHECK_INVARIANT(lringatoms.size() > 0, "no other ring atoms found.");
|
|
for (auto orae = rae + 1; orae != ringStereoAtoms.end(); ++orae) {
|
|
int oringAtomEntry = *orae;
|
|
int oringAtomIdx =
|
|
oringAtomEntry < 0 ? -oringAtomEntry - 1 : oringAtomEntry - 1;
|
|
int theseDifferent = (ringAtomEntry < 0) ^ (oringAtomEntry < 0);
|
|
lringatoms.push_back(theseDifferent ? -(oringAtomIdx + 1)
|
|
: (oringAtomIdx + 1));
|
|
INT_VECT olringatoms(0);
|
|
mol.getAtomWithIdx(oringAtomIdx)
|
|
->getPropIfPresent(common_properties::_ringStereoAtoms,
|
|
olringatoms);
|
|
CHECK_INVARIANT(olringatoms.size() > 0, "no other ring atoms found.");
|
|
olringatoms.push_back(theseDifferent ? -(ringAtomIdx + 1)
|
|
: (ringAtomIdx + 1));
|
|
mol.getAtomWithIdx(oringAtomIdx)
|
|
->setProp(common_properties::_ringStereoAtoms, olringatoms);
|
|
}
|
|
mol.getAtomWithIdx(ringAtomIdx)
|
|
->setProp(common_properties::_ringStereoAtoms, lringatoms);
|
|
}
|
|
|
|
} else {
|
|
possibleSpecialCases.reset(atom->getIdx());
|
|
}
|
|
atomsSeen.set(atom->getIdx());
|
|
}
|
|
}
|
|
|
|
std::pair<bool, bool> isAtomPotentialChiralCenter(
|
|
const Atom *atom, const ROMol &mol, const UINT_VECT &ranks,
|
|
Chirality::INT_PAIR_VECT &nbrs) {
|
|
// loop over all neighbors and form a decorated list of their
|
|
// ranks:
|
|
bool legalCenter = true;
|
|
bool hasDupes = false;
|
|
|
|
auto nzDegree = Chirality::detail::getAtomNonzeroDegree(atom);
|
|
auto tnzDegree = nzDegree + atom->getTotalNumHs();
|
|
if (tnzDegree > 4) {
|
|
// we only know tetrahedral chirality
|
|
legalCenter = false;
|
|
} else {
|
|
// cases we can exclude immediately without having to look at neighbors
|
|
// ranks:
|
|
if (tnzDegree < 3) {
|
|
legalCenter = false;
|
|
} else if (nzDegree < 3 &&
|
|
(atom->getAtomicNum() != 15 && atom->getAtomicNum() != 33)) {
|
|
// less than three neighbors is never stereogenic
|
|
// unless it is a phosphine/arsine with implicit H (this is from InChI)
|
|
legalCenter = false;
|
|
} else if (nzDegree == 3) {
|
|
if (atom->getTotalNumHs() == 1) {
|
|
// three-coordinate with more than one H is never stereogenic
|
|
if (detail::has_protium_neighbor(mol, atom)) {
|
|
legalCenter = false;
|
|
}
|
|
} else {
|
|
// assume something that's really three coordinate isn't potentially
|
|
// chiral, then look for exceptions
|
|
legalCenter = false;
|
|
if (atom->getAtomicNum() == 7) {
|
|
// three-coordinate N additional requirements:
|
|
// in a ring of size 3 (from InChI)
|
|
// OR
|
|
/// is a bridgehead atom (RDKit extension)
|
|
if (mol.getRingInfo()->isAtomInRingOfSize(atom->getIdx(), 3) ||
|
|
queryIsAtomBridgehead(atom)) {
|
|
legalCenter = true;
|
|
}
|
|
} else if (atom->getAtomicNum() == 15 || atom->getAtomicNum() == 33) {
|
|
// three-coordinate phosphines and arsines
|
|
// are always treated as stereogenic even with H atom neighbors.
|
|
// (this is from InChI)
|
|
legalCenter = true;
|
|
} else if (atom->getAtomicNum() == 16 || atom->getAtomicNum() == 34) {
|
|
if (atom->getExplicitValence() == 4 ||
|
|
(atom->getExplicitValence() == 3 &&
|
|
atom->getFormalCharge() == 1)) {
|
|
// we also accept sulfur or selenium with either a positive charge
|
|
// or a double bond:
|
|
legalCenter = true;
|
|
}
|
|
}
|
|
}
|
|
}
|
|
|
|
if (legalCenter) {
|
|
boost::dynamic_bitset<> codesSeen(mol.getNumAtoms());
|
|
for (const auto bond : mol.atomBonds(atom)) {
|
|
unsigned int otherIdx = bond->getOtherAtom(atom)->getIdx();
|
|
nbrs.push_back(std::make_pair(ranks[otherIdx], bond->getIdx()));
|
|
if (!Chirality::detail::bondAffectsAtomChirality(bond, atom)) {
|
|
continue;
|
|
}
|
|
CHECK_INVARIANT(ranks[otherIdx] < mol.getNumAtoms(),
|
|
"CIP rank higher than the number of atoms.");
|
|
// watch for neighbors with duplicate ranks, which would mean
|
|
// that we cannot be chiral:
|
|
if (codesSeen[ranks[otherIdx]]) {
|
|
// we've already seen this code, it's a dupe
|
|
hasDupes = true;
|
|
break;
|
|
}
|
|
codesSeen[ranks[otherIdx]] = 1;
|
|
}
|
|
}
|
|
}
|
|
return std::make_pair(legalCenter, hasDupes);
|
|
}
|
|
|
|
// returns a pair:
|
|
// 1) are there unassigned stereoatoms
|
|
// 2) did we assign any?
|
|
std::pair<bool, bool> assignAtomChiralCodes(ROMol &mol, UINT_VECT &ranks,
|
|
bool flagPossibleStereoCenters) {
|
|
PRECONDITION((!ranks.size() || ranks.size() == mol.getNumAtoms()),
|
|
"bad rank vector size");
|
|
bool atomChanged = false;
|
|
unsigned int unassignedAtoms = 0;
|
|
|
|
// ------------------
|
|
// now loop over each atom and, if it's marked as chiral,
|
|
// figure out the appropriate CIP label:
|
|
for (auto atom : mol.atoms()) {
|
|
Atom::ChiralType tag = atom->getChiralTag();
|
|
|
|
// only worry about this atom if it has a marked chirality
|
|
// we understand:
|
|
if (flagPossibleStereoCenters ||
|
|
(tag != Atom::CHI_UNSPECIFIED && tag != Atom::CHI_OTHER)) {
|
|
if (atom->hasProp(common_properties::_CIPCode)) {
|
|
continue;
|
|
}
|
|
|
|
if (!ranks.size()) {
|
|
// if we need to, get the "CIP" ranking of each atom:
|
|
assignAtomCIPRanks(mol, ranks);
|
|
}
|
|
Chirality::INT_PAIR_VECT nbrs;
|
|
// note that hasDupes is only evaluated if legalCenter==true
|
|
auto [legalCenter, hasDupes] =
|
|
isAtomPotentialChiralCenter(atom, mol, ranks, nbrs);
|
|
if (legalCenter) {
|
|
++unassignedAtoms;
|
|
}
|
|
if (legalCenter && !hasDupes && flagPossibleStereoCenters) {
|
|
atom->setProp(common_properties::_ChiralityPossible, 1);
|
|
}
|
|
|
|
if (legalCenter && !hasDupes && tag != Atom::CHI_UNSPECIFIED &&
|
|
tag != Atom::CHI_OTHER) {
|
|
// stereochem is possible and we have no duplicate neighbors, assign
|
|
// a CIP code:
|
|
atomChanged = true;
|
|
--unassignedAtoms;
|
|
|
|
// sort the list of neighbors by their CIP ranks:
|
|
std::sort(nbrs.begin(), nbrs.end(), Rankers::pairLess);
|
|
|
|
// collect the list of neighbor indices:
|
|
std::list<int> nbrIndices;
|
|
for (Chirality::INT_PAIR_VECT_CI nbrIt = nbrs.begin();
|
|
nbrIt != nbrs.end(); ++nbrIt) {
|
|
nbrIndices.push_back((*nbrIt).second);
|
|
}
|
|
// ask the atom how many swaps we have to make:
|
|
int nSwaps = atom->getPerturbationOrder(nbrIndices);
|
|
|
|
// if the atom has 3 neighbors and a hydrogen, add a swap:
|
|
if (nbrIndices.size() == 3 && atom->getTotalNumHs() == 1) {
|
|
++nSwaps;
|
|
}
|
|
|
|
// if that number is odd, we'll change our chirality:
|
|
if (nSwaps % 2) {
|
|
if (tag == Atom::CHI_TETRAHEDRAL_CCW) {
|
|
tag = Atom::CHI_TETRAHEDRAL_CW;
|
|
} else {
|
|
tag = Atom::CHI_TETRAHEDRAL_CCW;
|
|
}
|
|
}
|
|
// now assign the CIP code:
|
|
std::string cipCode;
|
|
if (tag == Atom::CHI_TETRAHEDRAL_CCW) {
|
|
cipCode = "S";
|
|
} else {
|
|
cipCode = "R";
|
|
}
|
|
atom->setProp(common_properties::_CIPCode, cipCode);
|
|
}
|
|
}
|
|
}
|
|
return std::make_pair((unassignedAtoms > 0), atomChanged);
|
|
}
|
|
|
|
// returns a pair:
|
|
// 1) are there unassigned stereo bonds?
|
|
// 2) did we assign any?
|
|
std::pair<bool, bool> assignBondStereoCodes(ROMol &mol, UINT_VECT &ranks) {
|
|
PRECONDITION((!ranks.size() || ranks.size() == mol.getNumAtoms()),
|
|
"bad rank vector size");
|
|
bool assignedABond = false;
|
|
unsigned int unassignedBonds = 0;
|
|
boost::dynamic_bitset<> bondsToClear(mol.getNumBonds());
|
|
// find the double bonds:
|
|
for (auto dblBond : mol.bonds()) {
|
|
if (dblBond->getBondType() == Bond::BondType::DOUBLE) {
|
|
if (dblBond->getStereo() != Bond::BondStereo::STEREONONE) {
|
|
continue;
|
|
}
|
|
if (!ranks.size()) {
|
|
assignAtomCIPRanks(mol, ranks);
|
|
}
|
|
dblBond->getStereoAtoms().clear();
|
|
|
|
// at the moment we are ignoring stereochem on ring bonds with less than
|
|
// 8 members.
|
|
if (shouldDetectDoubleBondStereo(dblBond)) {
|
|
const Atom *begAtom = dblBond->getBeginAtom();
|
|
const Atom *endAtom = dblBond->getEndAtom();
|
|
// we're only going to handle 2 or three coordinate atoms:
|
|
if ((begAtom->getDegree() == 2 || begAtom->getDegree() == 3) &&
|
|
(endAtom->getDegree() == 2 || endAtom->getDegree() == 3)) {
|
|
++unassignedBonds;
|
|
|
|
// look around each atom and see if it has at least one bond with
|
|
// direction marked:
|
|
|
|
// the pairs here are: atomIdx,bonddir
|
|
Chirality::INT_PAIR_VECT begAtomNeighbors, endAtomNeighbors;
|
|
bool hasExplicitUnknownStereo = false;
|
|
int bgn_stereo = false, end_stereo = false;
|
|
if ((dblBond->getBeginAtom()->getPropIfPresent(
|
|
common_properties::_UnknownStereo, bgn_stereo) &&
|
|
bgn_stereo) ||
|
|
(dblBond->getEndAtom()->getPropIfPresent(
|
|
common_properties::_UnknownStereo, end_stereo) &&
|
|
end_stereo)) {
|
|
hasExplicitUnknownStereo = true;
|
|
}
|
|
Chirality::findAtomNeighborDirHelper(mol, begAtom, dblBond, ranks,
|
|
begAtomNeighbors,
|
|
hasExplicitUnknownStereo);
|
|
Chirality::findAtomNeighborDirHelper(mol, endAtom, dblBond, ranks,
|
|
endAtomNeighbors,
|
|
hasExplicitUnknownStereo);
|
|
|
|
if (begAtomNeighbors.size() && endAtomNeighbors.size()) {
|
|
// Each atom has at least one neighboring bond with marked
|
|
// directionality. Find the highest-ranked directionality
|
|
// on each side:
|
|
|
|
int begDir, endDir, endNbrAid, begNbrAid;
|
|
if (begAtomNeighbors.size() == 1 ||
|
|
ranks[begAtomNeighbors[0].first] >
|
|
ranks[begAtomNeighbors[1].first]) {
|
|
begDir = begAtomNeighbors[0].second;
|
|
begNbrAid = begAtomNeighbors[0].first;
|
|
} else {
|
|
begDir = begAtomNeighbors[1].second;
|
|
begNbrAid = begAtomNeighbors[1].first;
|
|
}
|
|
if (endAtomNeighbors.size() == 1 ||
|
|
ranks[endAtomNeighbors[0].first] >
|
|
ranks[endAtomNeighbors[1].first]) {
|
|
endDir = endAtomNeighbors[0].second;
|
|
endNbrAid = endAtomNeighbors[0].first;
|
|
} else {
|
|
endDir = endAtomNeighbors[1].second;
|
|
endNbrAid = endAtomNeighbors[1].first;
|
|
}
|
|
|
|
bool conflictingBegin =
|
|
(begAtomNeighbors.size() == 2 &&
|
|
begAtomNeighbors[0].second == begAtomNeighbors[1].second);
|
|
bool conflictingEnd =
|
|
(endAtomNeighbors.size() == 2 &&
|
|
endAtomNeighbors[0].second == endAtomNeighbors[1].second);
|
|
if (conflictingBegin || conflictingEnd) {
|
|
dblBond->setStereo(Bond::STEREONONE);
|
|
BOOST_LOG(rdWarningLog) << "Conflicting single bond directions "
|
|
"around double bond at index "
|
|
<< dblBond->getIdx() << "." << std::endl;
|
|
BOOST_LOG(rdWarningLog) << " BondStereo set to STEREONONE and "
|
|
"single bond directions set to NONE."
|
|
<< std::endl;
|
|
assignedABond = true;
|
|
if (conflictingBegin) {
|
|
bondsToClear[mol.getBondBetweenAtoms(begAtomNeighbors[0].first,
|
|
begAtom->getIdx())
|
|
->getIdx()] = 1;
|
|
bondsToClear[mol.getBondBetweenAtoms(begAtomNeighbors[1].first,
|
|
begAtom->getIdx())
|
|
->getIdx()] = 1;
|
|
}
|
|
if (conflictingEnd) {
|
|
bondsToClear[mol.getBondBetweenAtoms(endAtomNeighbors[0].first,
|
|
endAtom->getIdx())
|
|
->getIdx()] = 1;
|
|
bondsToClear[mol.getBondBetweenAtoms(endAtomNeighbors[1].first,
|
|
endAtom->getIdx())
|
|
->getIdx()] = 1;
|
|
}
|
|
} else {
|
|
dblBond->getStereoAtoms().push_back(begNbrAid);
|
|
dblBond->getStereoAtoms().push_back(endNbrAid);
|
|
if (hasExplicitUnknownStereo) {
|
|
dblBond->setStereo(Bond::STEREOANY);
|
|
assignedABond = true;
|
|
} else if (begDir == endDir) {
|
|
// In findAtomNeighborDirHelper, we've set up the
|
|
// bond directions here so that they correspond to
|
|
// having both single bonds START at the double bond.
|
|
// This means that if the single bonds point in the same
|
|
// direction, the bond is cis, "Z"
|
|
dblBond->setStereo(Bond::STEREOZ);
|
|
assignedABond = true;
|
|
} else {
|
|
dblBond->setStereo(Bond::STEREOE);
|
|
assignedABond = true;
|
|
}
|
|
}
|
|
--unassignedBonds;
|
|
}
|
|
}
|
|
}
|
|
}
|
|
}
|
|
|
|
for (unsigned int i = 0; i < mol.getNumBonds(); ++i) {
|
|
if (bondsToClear[i]) {
|
|
mol.getBondWithIdx(i)->setBondDir(Bond::NONE);
|
|
}
|
|
}
|
|
|
|
return std::make_pair(unassignedBonds > 0, assignedABond);
|
|
}
|
|
|
|
void assignLegacyCIPLabels(ROMol &mol, bool flagPossibleStereoCenters) {
|
|
std::vector<unsigned int> atomRanks;
|
|
assignAtomChiralCodes(mol, atomRanks, flagPossibleStereoCenters);
|
|
|
|
// reset any already-specfied double bonds:
|
|
for (auto bond : mol.bonds()) {
|
|
if (bond->getBondType() == Bond::BondType::DOUBLE &&
|
|
bond->getStereo() > Bond::BondStereo::STEREOANY) {
|
|
bond->setStereo(Bond::BondStereo::STEREONONE);
|
|
}
|
|
}
|
|
assignBondStereoCodes(mol, atomRanks);
|
|
}
|
|
|
|
void assignBondCisTrans(ROMol &mol, const StereoInfo &sinfo) {
|
|
if (sinfo.type != StereoType::Bond_Double ||
|
|
sinfo.specified != StereoSpecified::Unspecified ||
|
|
sinfo.controllingAtoms.size() != 4) {
|
|
return;
|
|
}
|
|
|
|
auto dblBond = mol.getBondWithIdx(sinfo.centeredOn);
|
|
|
|
bool begFirstNeighbor = true;
|
|
auto begBond = mol.getBondBetweenAtoms(dblBond->getBeginAtomIdx(),
|
|
sinfo.controllingAtoms[0]);
|
|
CHECK_INVARIANT(begBond, "no initial bond found");
|
|
auto begDir = begBond->getBondDir();
|
|
if (begDir != Bond::BondDir::ENDDOWNRIGHT &&
|
|
begDir != Bond::BondDir::ENDUPRIGHT) {
|
|
begFirstNeighbor = false;
|
|
if (sinfo.controllingAtoms[1] != StereoInfo::NOATOM) {
|
|
begBond = mol.getBondBetweenAtoms(dblBond->getBeginAtomIdx(),
|
|
sinfo.controllingAtoms[1]);
|
|
CHECK_INVARIANT(begBond, "no initial bond found");
|
|
begDir = begBond->getBondDir();
|
|
}
|
|
}
|
|
// no direction found at beginning
|
|
if (begDir != Bond::BondDir::ENDDOWNRIGHT &&
|
|
begDir != Bond::BondDir::ENDUPRIGHT) {
|
|
return;
|
|
}
|
|
if (begBond->getBeginAtomIdx() != dblBond->getBeginAtomIdx()) {
|
|
begDir = begDir == Bond::BondDir::ENDDOWNRIGHT
|
|
? Bond::BondDir::ENDUPRIGHT
|
|
: Bond::BondDir::ENDDOWNRIGHT;
|
|
}
|
|
|
|
bool endFirstNeighbor = true;
|
|
auto endBond = mol.getBondBetweenAtoms(dblBond->getEndAtomIdx(),
|
|
sinfo.controllingAtoms[2]);
|
|
CHECK_INVARIANT(endBond, "no final bond found");
|
|
auto endDir = endBond->getBondDir();
|
|
if (endDir != Bond::BondDir::ENDDOWNRIGHT &&
|
|
endDir != Bond::BondDir::ENDUPRIGHT) {
|
|
endFirstNeighbor = false;
|
|
if (sinfo.controllingAtoms[3] != StereoInfo::NOATOM) {
|
|
endBond = mol.getBondBetweenAtoms(dblBond->getEndAtomIdx(),
|
|
sinfo.controllingAtoms[3]);
|
|
CHECK_INVARIANT(endBond, "no final bond found");
|
|
endDir = endBond->getBondDir();
|
|
}
|
|
}
|
|
// no direction found at end
|
|
if (endDir != Bond::BondDir::ENDDOWNRIGHT &&
|
|
endDir != Bond::BondDir::ENDUPRIGHT) {
|
|
return;
|
|
}
|
|
if (endBond->getBeginAtomIdx() != dblBond->getEndAtomIdx()) {
|
|
endDir = endDir == Bond::BondDir::ENDDOWNRIGHT
|
|
? Bond::BondDir::ENDUPRIGHT
|
|
: Bond::BondDir::ENDDOWNRIGHT;
|
|
}
|
|
|
|
// we've set up the bond directions here so that they correspond to having
|
|
// both single bonds START at the double bond. This means that if the single
|
|
// bonds point in the same direction, the bond is cis
|
|
bool sameDir = begDir == endDir;
|
|
|
|
// if either the direction bond at the beginning or the direction bond at the
|
|
// end wasn't to the first neighbor on that side (but not both), then we need
|
|
// to swap
|
|
if (begFirstNeighbor ^ endFirstNeighbor) {
|
|
sameDir = !sameDir;
|
|
}
|
|
|
|
dblBond->setStereoAtoms(sinfo.controllingAtoms[0], sinfo.controllingAtoms[2]);
|
|
if (sameDir) {
|
|
dblBond->setStereo(Bond::BondStereo::STEREOCIS);
|
|
} else {
|
|
dblBond->setStereo(Bond::BondStereo::STEREOTRANS);
|
|
}
|
|
}
|
|
|
|
// reassign atom ranks by supplementing the current ranks
|
|
// with information about known chirality
|
|
void rerankAtoms(const ROMol &mol, UINT_VECT &ranks) {
|
|
PRECONDITION(ranks.size() == mol.getNumAtoms(), "bad rank vector size");
|
|
unsigned int factor = 100;
|
|
while (factor < mol.getNumAtoms()) {
|
|
factor *= 10;
|
|
}
|
|
|
|
#ifdef VERBOSE_CANON
|
|
BOOST_LOG(rdDebugLog) << "rerank PRE: " << std::endl;
|
|
for (int i = 0; i < mol.getNumAtoms(); i++) {
|
|
BOOST_LOG(rdDebugLog) << " " << i << ": " << ranks[i] << std::endl;
|
|
}
|
|
#endif
|
|
|
|
DOUBLE_VECT invars(mol.getNumAtoms());
|
|
// and now supplement them:
|
|
for (unsigned int i = 0; i < mol.getNumAtoms(); ++i) {
|
|
invars[i] = ranks[i] * factor;
|
|
const Atom *atom = mol.getAtomWithIdx(i);
|
|
// Priority order: R > S > nothing
|
|
std::string cipCode;
|
|
if (atom->getPropIfPresent(common_properties::_CIPCode, cipCode)) {
|
|
if (cipCode == "S") {
|
|
invars[i] += 10;
|
|
} else if (cipCode == "R") {
|
|
invars[i] += 20;
|
|
}
|
|
}
|
|
for (const auto oBond : mol.atomBonds(atom)) {
|
|
if (oBond->getBondType() == Bond::DOUBLE) {
|
|
if (oBond->getStereo() == Bond::STEREOE) {
|
|
invars[i] += 1;
|
|
} else if (oBond->getStereo() == Bond::STEREOZ) {
|
|
invars[i] += 2;
|
|
}
|
|
}
|
|
}
|
|
}
|
|
iterateCIPRanks(mol, invars, ranks, true);
|
|
// copy the ranks onto the atoms:
|
|
for (unsigned int i = 0; i < mol.getNumAtoms(); i++) {
|
|
mol.getAtomWithIdx(i)->setProp(common_properties::_CIPRank, ranks[i]);
|
|
}
|
|
|
|
#ifdef VERBOSE_CANON
|
|
BOOST_LOG(rdDebugLog) << " post: " << std::endl;
|
|
for (int i = 0; i < mol.getNumAtoms(); i++) {
|
|
BOOST_LOG(rdDebugLog) << " " << i << ": " << ranks[i] << std::endl;
|
|
}
|
|
#endif
|
|
}
|
|
|
|
bool hasStereoBondDir(const Bond *bond) {
|
|
PRECONDITION(bond, "no bond");
|
|
return bond->getBondDir() == Bond::BondDir::ENDDOWNRIGHT ||
|
|
bond->getBondDir() == Bond::BondDir::ENDUPRIGHT;
|
|
}
|
|
|
|
const Bond *getNeighboringDirectedBond(const ROMol &mol, const Atom *atom) {
|
|
PRECONDITION(atom, "no atom");
|
|
for (const auto &bondIdx :
|
|
boost::make_iterator_range(mol.getAtomBonds(atom))) {
|
|
const Bond *bond = mol[bondIdx];
|
|
|
|
if (bond->getBondType() != Bond::BondType::DOUBLE &&
|
|
hasStereoBondDir(bond)) {
|
|
return bond;
|
|
}
|
|
}
|
|
return nullptr;
|
|
}
|
|
|
|
Bond::BondStereo translateEZLabelToCisTrans(Bond::BondStereo label) {
|
|
switch (label) {
|
|
case Bond::STEREOE:
|
|
return Bond::STEREOTRANS;
|
|
case Bond::STEREOZ:
|
|
return Bond::STEREOCIS;
|
|
default:
|
|
return label;
|
|
}
|
|
}
|
|
|
|
INT_VECT findStereoAtoms(const Bond *bond) {
|
|
PRECONDITION(bond, "bad bond");
|
|
PRECONDITION(bond->hasOwningMol(), "no mol");
|
|
PRECONDITION(bond->getBondType() == Bond::DOUBLE, "not double bond");
|
|
PRECONDITION(bond->getStereo() > Bond::BondStereo::STEREOANY,
|
|
"no defined stereo");
|
|
|
|
if (!bond->getStereoAtoms().empty()) {
|
|
return bond->getStereoAtoms();
|
|
}
|
|
if (bond->getStereo() == Bond::BondStereo::STEREOE ||
|
|
bond->getStereo() == Bond::BondStereo::STEREOZ) {
|
|
const Atom *startStereoAtom =
|
|
findHighestCIPNeighbor(bond->getBeginAtom(), bond->getEndAtom());
|
|
const Atom *endStereoAtom =
|
|
findHighestCIPNeighbor(bond->getEndAtom(), bond->getBeginAtom());
|
|
|
|
if (startStereoAtom == nullptr || endStereoAtom == nullptr) {
|
|
return {};
|
|
}
|
|
|
|
int startStereoAtomIdx = static_cast<int>(startStereoAtom->getIdx());
|
|
int endStereoAtomIdx = static_cast<int>(endStereoAtom->getIdx());
|
|
|
|
return {startStereoAtomIdx, endStereoAtomIdx};
|
|
} else {
|
|
BOOST_LOG(rdWarningLog) << "Unable to assign stereo atoms for bond "
|
|
<< bond->getIdx() << std::endl;
|
|
return {};
|
|
}
|
|
}
|
|
|
|
void cleanupStereoGroups(ROMol &mol) {
|
|
std::vector<StereoGroup> newsgs;
|
|
for (auto sg : mol.getStereoGroups()) {
|
|
std::vector<Atom *> okatoms;
|
|
bool keep = true;
|
|
for (const auto atom : sg.getAtoms()) {
|
|
if (atom->getChiralTag() == Atom::ChiralType::CHI_UNSPECIFIED) {
|
|
keep = false;
|
|
} else {
|
|
okatoms.push_back(atom);
|
|
}
|
|
}
|
|
|
|
if (keep) {
|
|
newsgs.push_back(sg);
|
|
} else if (!okatoms.empty()) {
|
|
newsgs.emplace_back(sg.getGroupType(), std::move(okatoms),
|
|
sg.getReadId());
|
|
}
|
|
}
|
|
mol.setStereoGroups(std::move(newsgs));
|
|
}
|
|
|
|
// ****************************************************************************
|
|
std::ostream &operator<<(std::ostream &oss, const StereoType &s) {
|
|
switch (s) {
|
|
case StereoType::Unspecified:
|
|
oss << "Unspecified";
|
|
break;
|
|
case StereoType::Atom_Tetrahedral:
|
|
oss << "Atom_Tetrahedral";
|
|
break;
|
|
case StereoType::Atom_SquarePlanar:
|
|
oss << "Atom_SquarePlanar";
|
|
break;
|
|
case StereoType::Atom_TrigonalBipyramidal:
|
|
oss << "Atom_TrigonalBipyramidal";
|
|
break;
|
|
case StereoType::Atom_Octahedral:
|
|
oss << "Atom_Octahedral";
|
|
break;
|
|
case StereoType::Bond_Double:
|
|
oss << "Bond_Double";
|
|
break;
|
|
case StereoType::Bond_Cumulene_Even:
|
|
oss << "Bond_Cumulene_Even";
|
|
break;
|
|
case StereoType::Bond_Atropisomer:
|
|
oss << "Bond_Atropisomer";
|
|
break;
|
|
}
|
|
return oss;
|
|
}
|
|
|
|
// ****************************************************************************
|
|
std::ostream &operator<<(std::ostream &oss, const StereoSpecified &s) {
|
|
switch (s) {
|
|
case StereoSpecified::Unspecified:
|
|
oss << "Unspecified";
|
|
break;
|
|
case StereoSpecified::Specified:
|
|
oss << "Specified";
|
|
break;
|
|
case StereoSpecified::Unknown:
|
|
oss << "Unknown";
|
|
break;
|
|
}
|
|
return oss;
|
|
}
|
|
|
|
/*
|
|
We're going to do this iteratively:
|
|
1) assign atom stereochemistry
|
|
2) assign bond stereochemistry
|
|
3) if there are still unresolved atoms or bonds
|
|
repeat the above steps as necessary
|
|
*/
|
|
void legacyStereoPerception(ROMol &mol, bool cleanIt,
|
|
bool flagPossibleStereoCenters) {
|
|
// later we're going to need ring information, get it now if we don't
|
|
// have it already:
|
|
if (!mol.getRingInfo()->isInitialized()) {
|
|
MolOps::fastFindRings(mol);
|
|
}
|
|
|
|
#if 0
|
|
std::cerr << ">>>>>>>>>>>>>\n";
|
|
std::cerr << "assign stereochem\n";
|
|
mol.debugMol(std::cerr);
|
|
#endif
|
|
|
|
// as part of the preparation, we'll loop over the atoms and
|
|
// bonds to see if anything has stereochemistry
|
|
// indicated. There's no point in doing the work here if there
|
|
// are neither stereocenters nor bonds that we need to consider.
|
|
// The exception to this is when flagPossibleStereoCenters is
|
|
// true; then we always need to do the work
|
|
bool hasStereoAtoms = flagPossibleStereoCenters;
|
|
for (auto atom : mol.atoms()) {
|
|
if (cleanIt) {
|
|
if (atom->hasProp(common_properties::_CIPCode)) {
|
|
atom->clearProp(common_properties::_CIPCode);
|
|
}
|
|
if (atom->hasProp(common_properties::_ChiralityPossible)) {
|
|
atom->clearProp(common_properties::_ChiralityPossible);
|
|
}
|
|
}
|
|
if (!hasStereoAtoms && atom->getChiralTag() != Atom::CHI_UNSPECIFIED &&
|
|
atom->getChiralTag() != Atom::CHI_OTHER) {
|
|
hasStereoAtoms = true;
|
|
}
|
|
}
|
|
bool hasStereoBonds = false;
|
|
for (auto bond : mol.bonds()) {
|
|
if (cleanIt) {
|
|
// enforce no stereo on small rings
|
|
if ((bond->getBondType() == Bond::DOUBLE ||
|
|
bond->getBondType() == Bond::AROMATIC) &&
|
|
!shouldDetectDoubleBondStereo(bond)) {
|
|
if (bond->getBondDir() == Bond::EITHERDOUBLE) {
|
|
bond->setBondDir(Bond::NONE);
|
|
}
|
|
if (bond->getStereo() != Bond::STEREONONE) {
|
|
bond->setStereo(Bond::STEREONONE);
|
|
bond->getStereoAtoms().clear();
|
|
}
|
|
continue;
|
|
} else if (bond->getBondType() == Bond::DOUBLE) {
|
|
if (bond->getBondDir() == Bond::EITHERDOUBLE) {
|
|
bond->setStereo(Bond::STEREOANY);
|
|
bond->getStereoAtoms().clear();
|
|
bond->setBondDir(Bond::NONE);
|
|
} else if (bond->getStereo() != Bond::STEREOANY) {
|
|
bond->setStereo(Bond::STEREONONE);
|
|
bond->getStereoAtoms().clear();
|
|
}
|
|
}
|
|
}
|
|
if (!hasStereoBonds && bond->getBondType() == Bond::DOUBLE) {
|
|
for (auto nbond : mol.atomBonds(bond->getBeginAtom())) {
|
|
if (nbond->getBondDir() == Bond::ENDDOWNRIGHT ||
|
|
nbond->getBondDir() == Bond::ENDUPRIGHT) {
|
|
hasStereoBonds = true;
|
|
break;
|
|
}
|
|
}
|
|
if (!hasStereoBonds) {
|
|
for (auto nbond : mol.atomBonds(bond->getEndAtom())) {
|
|
if (nbond->getBondDir() == Bond::ENDDOWNRIGHT ||
|
|
nbond->getBondDir() == Bond::ENDUPRIGHT) {
|
|
hasStereoBonds = true;
|
|
break;
|
|
}
|
|
}
|
|
}
|
|
}
|
|
if (!cleanIt && hasStereoBonds) {
|
|
break; // no reason to keep iterating if we've already
|
|
// determined there are stereo bonds to consider
|
|
}
|
|
}
|
|
UINT_VECT atomRanks;
|
|
bool keepGoing = hasStereoAtoms | hasStereoBonds;
|
|
bool changedStereoAtoms, changedStereoBonds;
|
|
while (keepGoing) {
|
|
if (hasStereoAtoms) {
|
|
std::tie(hasStereoAtoms, changedStereoAtoms) =
|
|
Chirality::assignAtomChiralCodes(mol, atomRanks,
|
|
flagPossibleStereoCenters);
|
|
} else {
|
|
changedStereoAtoms = false;
|
|
}
|
|
if (hasStereoBonds) {
|
|
std::tie(hasStereoBonds, changedStereoBonds) =
|
|
Chirality::assignBondStereoCodes(mol, atomRanks);
|
|
} else {
|
|
changedStereoBonds = false;
|
|
}
|
|
keepGoing = (hasStereoAtoms || hasStereoBonds) &&
|
|
(changedStereoAtoms || changedStereoBonds);
|
|
|
|
if (keepGoing) {
|
|
// update the atom ranks based on the new information we have:
|
|
Chirality::rerankAtoms(mol, atomRanks);
|
|
}
|
|
#if 0
|
|
std::cout << "*************** done iteration " << keepGoing
|
|
<< " ***********" << std::endl;
|
|
mol.debugMol(std::cout);
|
|
std::cout << "*************** done iteration " << keepGoing
|
|
<< " ***********" << std::endl;
|
|
#endif
|
|
}
|
|
|
|
if (cleanIt) {
|
|
// if the ranks are needed again, this will force them to be
|
|
// re-calculated based on the stereo calculated above.
|
|
// atomRanks.clear();
|
|
|
|
for (auto atom : mol.atoms()) {
|
|
if (atom->hasProp(common_properties::_ringStereochemCand)) {
|
|
atom->clearProp(common_properties::_ringStereochemCand);
|
|
}
|
|
if (atom->hasProp(common_properties::_ringStereoAtoms)) {
|
|
atom->clearProp(common_properties::_ringStereoAtoms);
|
|
}
|
|
}
|
|
boost::dynamic_bitset<> possibleSpecialCases(mol.getNumAtoms());
|
|
Chirality::findChiralAtomSpecialCases(mol, possibleSpecialCases);
|
|
|
|
for (auto atom : mol.atoms()) {
|
|
if (atom->getChiralTag() != Atom::CHI_UNSPECIFIED &&
|
|
!Chirality::hasNonTetrahedralStereo(atom) &&
|
|
!atom->hasProp(common_properties::_CIPCode) &&
|
|
(!possibleSpecialCases[atom->getIdx()] ||
|
|
!atom->hasProp(common_properties::_ringStereoAtoms))) {
|
|
atom->setChiralTag(Atom::CHI_UNSPECIFIED);
|
|
|
|
// If the atom has an explicit hydrogen and no charge, that H
|
|
// was probably put there solely because of the chirality.
|
|
// So we'll go ahead and remove it.
|
|
// This was Issue 194
|
|
if (atom->getNumExplicitHs() == 1 && atom->getFormalCharge() == 0 &&
|
|
!atom->getIsAromatic()) {
|
|
atom->setNumExplicitHs(0);
|
|
atom->setNoImplicit(false);
|
|
atom->calcExplicitValence(false);
|
|
atom->calcImplicitValence(false);
|
|
}
|
|
}
|
|
}
|
|
for (auto bond : mol.bonds()) {
|
|
// wedged bonds to atoms that have no stereochem
|
|
// should be removed. (github issue 87)
|
|
if ((bond->getBondDir() == Bond::BEGINWEDGE ||
|
|
bond->getBondDir() == Bond::BEGINDASH) &&
|
|
bond->getBeginAtom()->getChiralTag() == Atom::CHI_UNSPECIFIED &&
|
|
bond->getEndAtom()->getChiralTag() == Atom::CHI_UNSPECIFIED) {
|
|
bond->setBondDir(Bond::NONE);
|
|
}
|
|
|
|
// check for directionality on single bonds around
|
|
// double bonds without stereo. This was github #2422
|
|
if (bond->getBondType() == Bond::DOUBLE &&
|
|
(bond->getStereo() == Bond::STEREOANY ||
|
|
bond->getStereo() == Bond::STEREONONE)) {
|
|
std::vector<Atom *> batoms = {bond->getBeginAtom(), bond->getEndAtom()};
|
|
for (auto batom : batoms) {
|
|
for (const auto nbrBndI : mol.atomBonds(batom)) {
|
|
if (nbrBndI == bond) {
|
|
continue;
|
|
}
|
|
if ((nbrBndI->getBondDir() == Bond::ENDDOWNRIGHT ||
|
|
nbrBndI->getBondDir() == Bond::ENDUPRIGHT) &&
|
|
(nbrBndI->getBondType() == Bond::SINGLE ||
|
|
nbrBndI->getBondType() == Bond::AROMATIC)) {
|
|
// direction is set, and we know it's not because of our
|
|
// bond. What about other neighbors?
|
|
bool okToClear = true;
|
|
for (const auto nbrBndJ :
|
|
mol.atomBonds(nbrBndI->getOtherAtom(batom))) {
|
|
if (nbrBndJ->getBondType() == Bond::DOUBLE &&
|
|
nbrBndJ->getStereo() != Bond::STEREOANY &&
|
|
nbrBndJ->getStereo() != Bond::STEREONONE) {
|
|
okToClear = false;
|
|
break;
|
|
}
|
|
}
|
|
if (okToClear) {
|
|
nbrBndI->setBondDir(Bond::NONE);
|
|
}
|
|
}
|
|
}
|
|
}
|
|
}
|
|
}
|
|
Chirality::cleanupStereoGroups(mol);
|
|
}
|
|
}
|
|
|
|
void updateDoubleBondStereo(ROMol &mol, const std::vector<StereoInfo> &sinfo,
|
|
bool cleanIt) {
|
|
boost::dynamic_bitset<> bondsTouched(mol.getNumBonds(), 0);
|
|
for (const auto &si : sinfo) {
|
|
if (si.type == Chirality::StereoType::Bond_Double) {
|
|
auto bond = mol.getBondWithIdx(si.centeredOn);
|
|
bondsTouched.set(bond->getIdx());
|
|
bond->setStereo(Bond::BondStereo::STEREONONE);
|
|
if (si.specified == Chirality::StereoSpecified::Specified) {
|
|
TEST_ASSERT(si.controllingAtoms.size() == 4);
|
|
bond->setStereoAtoms(si.controllingAtoms[0], si.controllingAtoms[2]);
|
|
switch (si.descriptor) {
|
|
case Chirality::StereoDescriptor::Bond_Cis:
|
|
bond->setStereo(Bond::BondStereo::STEREOCIS);
|
|
break;
|
|
case Chirality::StereoDescriptor::Bond_Trans:
|
|
bond->setStereo(Bond::BondStereo::STEREOTRANS);
|
|
break;
|
|
default:
|
|
BOOST_LOG(rdWarningLog)
|
|
<< "unrecognized bond stereo type" << std::endl;
|
|
}
|
|
} else if (si.specified == Chirality::StereoSpecified::Unknown) {
|
|
bond->setStereo(Bond::BondStereo::STEREOANY);
|
|
bond->getStereoAtoms().clear();
|
|
bond->setBondDir(Bond::BondDir::NONE);
|
|
} else if (si.specified == Chirality::StereoSpecified::Unspecified) {
|
|
assignBondCisTrans(mol, si);
|
|
}
|
|
}
|
|
}
|
|
if (cleanIt) {
|
|
for (auto bond : mol.bonds()) {
|
|
if (bondsTouched[bond->getIdx()] ||
|
|
bond->getBondType() != Bond::BondType::DOUBLE) {
|
|
continue;
|
|
}
|
|
// we didn't see it above, so it can't have stereo:
|
|
bond->setStereo(Bond::BondStereo::STEREONONE);
|
|
bond->setBondDir(Bond::BondDir::NONE);
|
|
bond->getStereoAtoms().clear();
|
|
}
|
|
}
|
|
}
|
|
void stereoPerception(ROMol &mol, bool cleanIt,
|
|
bool flagPossibleStereoCenters) {
|
|
if (cleanIt) {
|
|
for (auto atom : mol.atoms()) {
|
|
atom->clearProp(common_properties::_CIPCode);
|
|
atom->clearProp(common_properties::_ChiralityPossible);
|
|
}
|
|
for (auto bond : mol.bonds()) {
|
|
if (bond->getBondDir() == Bond::BondDir::EITHERDOUBLE) {
|
|
bond->setStereo(Bond::BondStereo::STEREOANY);
|
|
bond->getStereoAtoms().clear();
|
|
bond->setBondDir(Bond::BondDir::NONE);
|
|
}
|
|
}
|
|
}
|
|
// we need cis/trans markers on the double bonds... set those now:
|
|
MolOps::setBondStereoFromDirections(mol);
|
|
|
|
// do the actual perception
|
|
auto sinfo =
|
|
Chirality::findPotentialStereo(mol, cleanIt, flagPossibleStereoCenters);
|
|
|
|
if (flagPossibleStereoCenters) {
|
|
for (const auto &si : sinfo) {
|
|
if (si.type == Chirality::StereoType::Atom_Tetrahedral ||
|
|
si.type == Chirality::StereoType::Atom_SquarePlanar ||
|
|
si.type == Chirality::StereoType::Atom_TrigonalBipyramidal ||
|
|
si.type == Chirality::StereoType::Atom_Octahedral) {
|
|
mol.getAtomWithIdx(si.centeredOn)
|
|
->setProp(common_properties::_ChiralityPossible, 1);
|
|
}
|
|
}
|
|
}
|
|
// populate double bond stereo info:
|
|
updateDoubleBondStereo(mol, sinfo, cleanIt);
|
|
if (cleanIt) {
|
|
Chirality::cleanupStereoGroups(mol);
|
|
}
|
|
}
|
|
} // namespace Chirality
|
|
|
|
namespace MolOps {
|
|
|
|
void assignStereochemistry(ROMol &mol, bool cleanIt, bool force,
|
|
bool flagPossibleStereoCenters) {
|
|
if (!force && mol.hasProp(common_properties::_StereochemDone)) {
|
|
return;
|
|
}
|
|
|
|
if (!Chirality::getUseLegacyStereoPerception()) {
|
|
Chirality::stereoPerception(mol, cleanIt, flagPossibleStereoCenters);
|
|
} else {
|
|
Chirality::legacyStereoPerception(mol, cleanIt, flagPossibleStereoCenters);
|
|
}
|
|
mol.setProp(common_properties::_StereochemDone, 1, true);
|
|
}
|
|
|
|
// Find bonds than can be cis/trans in a molecule and mark them as
|
|
// Bond::STEREOANY.
|
|
void findPotentialStereoBonds(ROMol &mol, bool cleanIt) {
|
|
// FIX: The earlier thought was to provide an optional argument to ignore or
|
|
// consider
|
|
// double bonds in a ring. But I am removing this optional argument and
|
|
// ignoring ring bonds
|
|
// completely for now. This is because finding a potential stereo bond in a
|
|
// ring involves
|
|
// more than just checking the CIPranks for the neighbors - SP 05/04/04
|
|
|
|
// make this function callable multiple times
|
|
if ((mol.hasProp(common_properties::_BondsPotentialStereo)) && (!cleanIt)) {
|
|
return;
|
|
} else {
|
|
UINT_VECT ranks;
|
|
ranks.resize(mol.getNumAtoms());
|
|
bool cipDone = false;
|
|
|
|
ROMol::BondIterator bondIt;
|
|
for (bondIt = mol.beginBonds(); bondIt != mol.endBonds(); ++bondIt) {
|
|
if ((*bondIt)->getBondType() == Bond::DOUBLE &&
|
|
!(mol.getRingInfo()->numBondRings((*bondIt)->getIdx()))) {
|
|
// we are ignoring ring bonds here - read the FIX above
|
|
Bond *dblBond = *bondIt;
|
|
// proceed only if we either want to clean the stereocode on this bond,
|
|
// if none is set on it yet, or it is STEREOANY and we need to find
|
|
// stereoatoms
|
|
if (cleanIt || dblBond->getStereo() == Bond::STEREONONE ||
|
|
(dblBond->getStereo() == Bond::STEREOANY &&
|
|
dblBond->getStereoAtoms().size() != 2)) {
|
|
dblBond->setStereo(Bond::STEREONONE);
|
|
const Atom *begAtom = dblBond->getBeginAtom(),
|
|
*endAtom = dblBond->getEndAtom();
|
|
// we're only going to handle 2 or three coordinate atoms:
|
|
if ((begAtom->getDegree() == 2 || begAtom->getDegree() == 3) &&
|
|
(endAtom->getDegree() == 2 || endAtom->getDegree() == 3)) {
|
|
// ------------------
|
|
// get the CIP ranking of each atom if we need it:
|
|
if (!cipDone) {
|
|
if (!begAtom->hasProp(common_properties::_CIPRank)) {
|
|
Chirality::assignAtomCIPRanks(mol, ranks);
|
|
} else {
|
|
// no need to recompute if we don't need to recompute. :-)
|
|
for (unsigned int ai = 0; ai < mol.getNumAtoms(); ++ai) {
|
|
ranks[ai] = mol.getAtomWithIdx(ai)->getProp<unsigned int>(
|
|
common_properties::_CIPRank);
|
|
}
|
|
}
|
|
cipDone = true;
|
|
}
|
|
// find the neighbors for the begin atom and the endAtom
|
|
UINT_VECT begAtomNeighbors, endAtomNeighbors;
|
|
bool checkDir = false;
|
|
bool includeAromatic = true;
|
|
Chirality::findAtomNeighborsHelper(mol, begAtom, dblBond,
|
|
begAtomNeighbors, checkDir,
|
|
includeAromatic);
|
|
Chirality::findAtomNeighborsHelper(mol, endAtom, dblBond,
|
|
endAtomNeighbors, checkDir,
|
|
includeAromatic);
|
|
if (begAtomNeighbors.size() > 0 && endAtomNeighbors.size() > 0) {
|
|
if ((begAtomNeighbors.size() == 2) &&
|
|
(endAtomNeighbors.size() == 2)) {
|
|
// if both of the atoms have 2 neighbors (other than the one
|
|
// connected
|
|
// by the double bond) and ....
|
|
#if 0
|
|
std::cerr << "Bond: " << dblBond->getIdx() << " "
|
|
<< begAtom->getIdx() << "=" << endAtom->getIdx()
|
|
<< std::endl;
|
|
std::cerr << " " << begAtomNeighbors[0] << "="
|
|
<< ranks[begAtomNeighbors[0]] << ":";
|
|
std::cerr << " " << begAtomNeighbors[1] << "="
|
|
<< ranks[begAtomNeighbors[1]] << std::endl;
|
|
std::cerr << " " << endAtomNeighbors[0] << "="
|
|
<< ranks[endAtomNeighbors[0]] << ":";
|
|
std::cerr << " " << endAtomNeighbors[1] << "="
|
|
<< ranks[endAtomNeighbors[1]] << std::endl;
|
|
#endif
|
|
if ((ranks[begAtomNeighbors[0]] !=
|
|
ranks[begAtomNeighbors[1]]) &&
|
|
(ranks[endAtomNeighbors[0]] !=
|
|
ranks[endAtomNeighbors[1]])) {
|
|
// the neighbors ranks are different at both the ends,
|
|
// this bond can be part of a cis/trans system
|
|
if (ranks[begAtomNeighbors[0]] > ranks[begAtomNeighbors[1]]) {
|
|
dblBond->getStereoAtoms().push_back(begAtomNeighbors[0]);
|
|
} else {
|
|
dblBond->getStereoAtoms().push_back(begAtomNeighbors[1]);
|
|
}
|
|
if (ranks[endAtomNeighbors[0]] > ranks[endAtomNeighbors[1]]) {
|
|
dblBond->getStereoAtoms().push_back(endAtomNeighbors[0]);
|
|
} else {
|
|
dblBond->getStereoAtoms().push_back(endAtomNeighbors[1]);
|
|
}
|
|
}
|
|
} else if (begAtomNeighbors.size() == 2) {
|
|
// if the begAtom has two neighbors and ....
|
|
if (ranks[begAtomNeighbors[0]] != ranks[begAtomNeighbors[1]]) {
|
|
// their ranks are different
|
|
if (ranks[begAtomNeighbors[0]] > ranks[begAtomNeighbors[1]]) {
|
|
dblBond->getStereoAtoms().push_back(begAtomNeighbors[0]);
|
|
} else {
|
|
dblBond->getStereoAtoms().push_back(begAtomNeighbors[1]);
|
|
}
|
|
dblBond->getStereoAtoms().push_back(endAtomNeighbors[0]);
|
|
}
|
|
} else if (endAtomNeighbors.size() == 2) {
|
|
// if the endAtom has two neighbors and ...
|
|
if (ranks[endAtomNeighbors[0]] != ranks[endAtomNeighbors[1]]) {
|
|
// their ranks are different
|
|
dblBond->getStereoAtoms().push_back(begAtomNeighbors[0]);
|
|
if (ranks[endAtomNeighbors[0]] > ranks[endAtomNeighbors[1]]) {
|
|
dblBond->getStereoAtoms().push_back(endAtomNeighbors[0]);
|
|
} else {
|
|
dblBond->getStereoAtoms().push_back(endAtomNeighbors[1]);
|
|
}
|
|
}
|
|
} else {
|
|
// end and beg atoms has only one neighbor each, it doesn't
|
|
// matter what the ranks are:
|
|
dblBond->getStereoAtoms().push_back(begAtomNeighbors[0]);
|
|
dblBond->getStereoAtoms().push_back(endAtomNeighbors[0]);
|
|
} // end of different number of neighbors on beg and end atoms
|
|
|
|
// mark this double bond as a potential stereo bond
|
|
if (!dblBond->getStereoAtoms().empty()) {
|
|
dblBond->setStereo(Bond::STEREOANY);
|
|
}
|
|
} // end of check that beg and end atoms have at least 1
|
|
// neighbor:
|
|
} // end of 2 and 3 coordinated atoms only
|
|
} // end of we want it or CIP code is not set
|
|
} // end of double bond
|
|
} // end of for loop over all bonds
|
|
mol.setProp(common_properties::_BondsPotentialStereo, 1, true);
|
|
}
|
|
}
|
|
|
|
// removes chirality markers from sp and sp2 hybridized centers:
|
|
void cleanupChirality(RWMol &mol) {
|
|
unsigned int degree, perm;
|
|
for (auto atom : mol.atoms()) {
|
|
switch (atom->getChiralTag()) {
|
|
case Atom::CHI_TETRAHEDRAL_CW:
|
|
case Atom::CHI_TETRAHEDRAL_CCW:
|
|
if (atom->getHybridization() != Atom::SP3) {
|
|
atom->setChiralTag(Atom::CHI_UNSPECIFIED);
|
|
}
|
|
break;
|
|
|
|
case Atom::CHI_TETRAHEDRAL:
|
|
if (atom->getHybridization() != Atom::SP3) {
|
|
atom->setChiralTag(Atom::CHI_UNSPECIFIED);
|
|
} else {
|
|
perm = 0;
|
|
atom->getPropIfPresent(common_properties::_chiralPermutation, perm);
|
|
if (perm > 2) {
|
|
perm = 0;
|
|
atom->setProp(common_properties::_chiralPermutation, perm);
|
|
}
|
|
}
|
|
break;
|
|
|
|
case Atom::CHI_SQUAREPLANAR:
|
|
degree = atom->getTotalDegree();
|
|
if (degree < 2 || degree > 4) {
|
|
atom->setChiralTag(Atom::CHI_UNSPECIFIED);
|
|
} else {
|
|
perm = 0;
|
|
atom->getPropIfPresent(common_properties::_chiralPermutation, perm);
|
|
if (perm > 3) {
|
|
perm = 0;
|
|
atom->setProp(common_properties::_chiralPermutation, perm);
|
|
}
|
|
}
|
|
break;
|
|
|
|
case Atom::CHI_TRIGONALBIPYRAMIDAL:
|
|
degree = atom->getTotalDegree();
|
|
if (degree < 2 || degree > 5) {
|
|
atom->setChiralTag(Atom::CHI_UNSPECIFIED);
|
|
} else {
|
|
perm = 0;
|
|
atom->getPropIfPresent(common_properties::_chiralPermutation, perm);
|
|
if (perm > 20) {
|
|
perm = 0;
|
|
atom->setProp(common_properties::_chiralPermutation, perm);
|
|
}
|
|
}
|
|
break;
|
|
|
|
case Atom::CHI_OCTAHEDRAL:
|
|
degree = atom->getTotalDegree();
|
|
if (degree < 2 || degree > 6) {
|
|
atom->setChiralTag(Atom::CHI_UNSPECIFIED);
|
|
} else {
|
|
perm = 0;
|
|
atom->getPropIfPresent(common_properties::_chiralPermutation, perm);
|
|
if (perm > 30) {
|
|
perm = 0;
|
|
atom->setProp(common_properties::_chiralPermutation, perm);
|
|
}
|
|
}
|
|
break;
|
|
|
|
default:
|
|
/* ??? Handle other types in future. */
|
|
break;
|
|
}
|
|
}
|
|
}
|
|
|
|
#define VOLTEST(X, Y, Z) (v[X].dotProduct(v[Y].crossProduct(v[Z])) >= 0.0)
|
|
|
|
static unsigned int OctahedralPermFrom3D(unsigned char *pair,
|
|
const RDGeom::Point3D *v) {
|
|
switch (pair[0]) {
|
|
case 2: // a-b
|
|
switch (pair[2]) {
|
|
case 4:
|
|
return VOLTEST(0, 3, 4) ? 28 : 27;
|
|
case 5:
|
|
return VOLTEST(0, 2, 3) ? 25 : 30;
|
|
default: // 0 or 6
|
|
return VOLTEST(0, 2, 3) ? 26 : 29;
|
|
}
|
|
break;
|
|
case 3: // a-c
|
|
switch (pair[1]) {
|
|
case 4:
|
|
return VOLTEST(0, 3, 4) ? 22 : 21;
|
|
case 5:
|
|
return VOLTEST(0, 1, 3) ? 19 : 24;
|
|
default: // 0 or 6
|
|
return VOLTEST(0, 1, 3) ? 20 : 23;
|
|
}
|
|
break;
|
|
case 4: // a-d
|
|
switch (pair[1]) {
|
|
case 3:
|
|
return VOLTEST(0, 2, 4) ? 13 : 12;
|
|
case 5:
|
|
return VOLTEST(0, 1, 2) ? 6 : 18;
|
|
default: // 0 or 6
|
|
return VOLTEST(0, 1, 2) ? 7 : 17;
|
|
}
|
|
break;
|
|
case 5: // a-e
|
|
switch (pair[1]) {
|
|
case 3:
|
|
return VOLTEST(0, 2, 3) ? 11 : 9;
|
|
case 4:
|
|
return VOLTEST(0, 1, 2) ? 3 : 16;
|
|
default: // 0 or 6
|
|
return VOLTEST(0, 1, 2) ? 5 : 15;
|
|
}
|
|
break;
|
|
default: // 0 or 6 a-f
|
|
switch (pair[1]) {
|
|
case 3:
|
|
return VOLTEST(0, 2, 3) ? 10 : 8;
|
|
case 4:
|
|
return VOLTEST(0, 1, 2) ? 1 : 2;
|
|
default: // 5
|
|
return VOLTEST(0, 1, 2) ? 4 : 14;
|
|
}
|
|
}
|
|
// unreachable
|
|
return 0;
|
|
}
|
|
|
|
bool isWigglyBond(const Bond *bond, const Atom *atom) {
|
|
int hasWigglyBond = 0;
|
|
if (bond->getBeginAtomIdx() == atom->getIdx() &&
|
|
bond->getBondType() == Bond::BondType::SINGLE &&
|
|
(bond->getBondDir() == Bond::BondDir::UNKNOWN ||
|
|
(bond->getPropIfPresent<int>(common_properties::_UnknownStereo,
|
|
hasWigglyBond) &&
|
|
hasWigglyBond))) {
|
|
return true;
|
|
}
|
|
return false;
|
|
}
|
|
// The tolerance here is pretty high in order to accomodate things coming from
|
|
// the dgeom code As we get more experience with real-world structures and/or
|
|
// improve the dgeom code, we can think about lowering this.
|
|
static bool assignNontetrahedralChiralTypeFrom3D(ROMol &mol,
|
|
const Conformer &conf,
|
|
Atom *atom,
|
|
double tolerance = 0.1) {
|
|
// FIX: add tests for dative and zero order bonds
|
|
// Fail fast check for non-tetrahedral elements
|
|
if (atom->getAtomicNum() < 15) {
|
|
return false;
|
|
}
|
|
|
|
// check for wiggly bonds
|
|
for (const auto bond : mol.atomBonds(atom)) {
|
|
if (isWigglyBond(bond, atom)) {
|
|
return false;
|
|
}
|
|
}
|
|
RDGeom::Point3D cen = conf.getAtomPos(atom->getIdx());
|
|
RDGeom::Point3D v[6];
|
|
unsigned int count = 0;
|
|
|
|
ROMol::ADJ_ITER nbrIdx, endNbrs;
|
|
boost::tie(nbrIdx, endNbrs) = mol.getAtomNeighbors(atom);
|
|
while (nbrIdx != endNbrs) {
|
|
if (count == 6) {
|
|
return false;
|
|
}
|
|
RDGeom::Point3D p = conf.getAtomPos(*nbrIdx);
|
|
v[count] = cen.directionVector(p);
|
|
++count;
|
|
++nbrIdx;
|
|
}
|
|
|
|
if (count < 3) {
|
|
return false;
|
|
}
|
|
|
|
unsigned char pair[6];
|
|
memset(pair, 0, 6);
|
|
|
|
unsigned int pairs = 0;
|
|
for (unsigned int i = 0; i < count; i++) {
|
|
for (unsigned int j = i + 1; j < count; j++) {
|
|
if (v[i].dotProduct(v[j]) < -(1 - tolerance)) {
|
|
if (pair[i] || pair[j]) {
|
|
return false;
|
|
}
|
|
pair[i] = j + 1;
|
|
pair[j] = i + 1;
|
|
pairs++;
|
|
}
|
|
}
|
|
}
|
|
|
|
#if 0
|
|
printf("count=%u pairs=%u [%u,%u,%u,%u,%u,%u]\n", count, pairs,
|
|
pair[0], pair[1], pair[2], pair[3], pair[4], pair[5]);
|
|
#endif
|
|
|
|
Atom::ChiralType tag;
|
|
unsigned int perm;
|
|
bool res = false;
|
|
switch (pairs) {
|
|
case 0:
|
|
break;
|
|
case 1:
|
|
switch (count) {
|
|
case 3: /* T-shape */
|
|
atom->setChiralTag(Atom::ChiralType::CHI_SQUAREPLANAR);
|
|
res = true;
|
|
if (pair[0] == 0) {
|
|
perm = 3; // Z
|
|
} else if (pair[0] == 2) {
|
|
perm = 2; // 4
|
|
} else /* pair[0] == 3 */ {
|
|
perm = 1; // U
|
|
}
|
|
atom->setProp(common_properties::_chiralPermutation, perm);
|
|
break;
|
|
case 4: /* See-saw */
|
|
if (pair[0] == 2) { // a b
|
|
if (v[2].angleTo(v[3]) < 100 * M_PI / 180.0) {
|
|
tag = Atom::ChiralType::CHI_OCTAHEDRAL;
|
|
perm = VOLTEST(0, 2, 3) ? 25 : 29;
|
|
} else {
|
|
tag = Atom::ChiralType::CHI_TRIGONALBIPYRAMIDAL;
|
|
perm = VOLTEST(0, 2, 3) ? 7 : 8;
|
|
}
|
|
} else if (pair[0] == 3) { // a c
|
|
if (v[1].angleTo(v[3]) < 100 * M_PI / 180.0) {
|
|
tag = Atom::ChiralType::CHI_OCTAHEDRAL;
|
|
perm = VOLTEST(0, 1, 3) ? 19 : 23;
|
|
} else {
|
|
tag = Atom::ChiralType::CHI_TRIGONALBIPYRAMIDAL;
|
|
perm = VOLTEST(0, 1, 3) ? 5 : 6;
|
|
}
|
|
} else if (pair[0] == 4) { // a d
|
|
if (v[1].angleTo(v[2]) < 100 * M_PI / 180.0) {
|
|
tag = Atom::ChiralType::CHI_OCTAHEDRAL;
|
|
perm = VOLTEST(0, 1, 2) ? 6 : 17;
|
|
} else {
|
|
tag = Atom::ChiralType::CHI_TRIGONALBIPYRAMIDAL;
|
|
perm = VOLTEST(0, 1, 2) ? 3 : 4;
|
|
}
|
|
} else if (pair[1] == 3) { // b c
|
|
if (v[0].angleTo(v[3]) < 100 * M_PI / 180.0) {
|
|
tag = Atom::ChiralType::CHI_OCTAHEDRAL;
|
|
perm = VOLTEST(0, 1, 3) ? 10 : 8;
|
|
} else {
|
|
tag = Atom::ChiralType::CHI_TRIGONALBIPYRAMIDAL;
|
|
perm = VOLTEST(1, 0, 3) ? 13 : 14;
|
|
}
|
|
} else if (pair[1] == 4) { // b d
|
|
if (v[0].angleTo(v[2]) < 100 * M_PI / 180.0) {
|
|
tag = Atom::ChiralType::CHI_OCTAHEDRAL;
|
|
perm = VOLTEST(0, 1, 3) ? 1 : 2;
|
|
} else {
|
|
tag = Atom::ChiralType::CHI_TRIGONALBIPYRAMIDAL;
|
|
perm = VOLTEST(1, 0, 2) ? 10 : 12;
|
|
}
|
|
} else /* pair[2] == 4 */ { // c d
|
|
if (v[0].angleTo(v[1]) < 100 * M_PI / 180.0) {
|
|
tag = Atom::ChiralType::CHI_OCTAHEDRAL;
|
|
perm = VOLTEST(0, 1, 3) ? 4 : 14;
|
|
} else {
|
|
tag = Atom::ChiralType::CHI_TRIGONALBIPYRAMIDAL;
|
|
perm = VOLTEST(3, 0, 1) ? 16 : 19;
|
|
}
|
|
}
|
|
atom->setChiralTag(tag);
|
|
res = true;
|
|
atom->setProp(common_properties::_chiralPermutation, perm);
|
|
break;
|
|
case 5: /* Trigonal bipyramidal */
|
|
atom->setChiralTag(Atom::ChiralType::CHI_TRIGONALBIPYRAMIDAL);
|
|
res = true;
|
|
if (pair[0] == 2) {
|
|
perm = VOLTEST(0, 2, 3) ? 7 : 8; // a b
|
|
} else if (pair[0] == 3) {
|
|
perm = VOLTEST(0, 1, 3) ? 5 : 6; // a c
|
|
} else if (pair[0] == 4) {
|
|
perm = VOLTEST(0, 1, 2) ? 3 : 4; // a d
|
|
} else if (pair[0] == 5) {
|
|
perm = VOLTEST(0, 1, 2) ? 1 : 2; // a e
|
|
} else if (pair[1] == 3) {
|
|
perm = VOLTEST(1, 0, 3) ? 13 : 14; // b c
|
|
} else if (pair[1] == 4) {
|
|
perm = VOLTEST(1, 0, 2) ? 10 : 12; // b d
|
|
} else if (pair[1] == 5) {
|
|
perm = VOLTEST(1, 0, 2) ? 9 : 11; // b e
|
|
} else if (pair[2] == 4) {
|
|
perm = VOLTEST(2, 0, 1) ? 16 : 19; // c d
|
|
} else if (pair[2] == 5) {
|
|
perm = VOLTEST(2, 0, 1) ? 15 : 20; // c e
|
|
} else /* pair[2] == 4 */ {
|
|
perm = VOLTEST(3, 0, 1) ? 17 : 18; // d e
|
|
}
|
|
atom->setProp(common_properties::_chiralPermutation, perm);
|
|
break;
|
|
}
|
|
break;
|
|
case 2:
|
|
if (count == 4) {
|
|
/* Square planar */
|
|
atom->setChiralTag(Atom::ChiralType::CHI_SQUAREPLANAR);
|
|
res = true;
|
|
if (pair[0] == 2) {
|
|
perm = 2; // 4
|
|
} else if (pair[0] == 3) {
|
|
perm = 1; // U
|
|
} else /* pair[1] == 4 */ {
|
|
perm = 3; // Z
|
|
}
|
|
atom->setProp(common_properties::_chiralPermutation, perm);
|
|
} else if (count == 5) {
|
|
/* Square pyramidal */
|
|
atom->setChiralTag(Atom::ChiralType::CHI_OCTAHEDRAL);
|
|
res = true;
|
|
perm = OctahedralPermFrom3D(pair, v);
|
|
atom->setProp(common_properties::_chiralPermutation, perm);
|
|
}
|
|
break;
|
|
case 3:
|
|
if (count == 6) {
|
|
/* Octahedral */
|
|
atom->setChiralTag(Atom::ChiralType::CHI_OCTAHEDRAL);
|
|
res = true;
|
|
perm = OctahedralPermFrom3D(pair, v);
|
|
atom->setProp(common_properties::_chiralPermutation, perm);
|
|
}
|
|
break;
|
|
}
|
|
return res;
|
|
}
|
|
|
|
void assignChiralTypesFrom3D(ROMol &mol, int confId, bool replaceExistingTags) {
|
|
const double ZERO_VOLUME_TOL = 0.1;
|
|
if (!mol.getNumConformers()) {
|
|
return;
|
|
}
|
|
const Conformer &conf = mol.getConformer(confId);
|
|
if (!conf.is3D()) {
|
|
return;
|
|
}
|
|
|
|
// if the molecule already has stereochemistry
|
|
// perceived, remove the flags that indicate
|
|
// this... what we're about to do will require
|
|
// that we go again.
|
|
if (mol.hasProp(common_properties::_StereochemDone)) {
|
|
mol.clearProp(common_properties::_StereochemDone);
|
|
}
|
|
|
|
auto allowNontetrahedralStereo = Chirality::getAllowNontetrahedralChirality();
|
|
for (auto atom : mol.atoms()) {
|
|
// if we aren't replacing existing tags and the atom is already tagged,
|
|
// punt:
|
|
if (!replaceExistingTags && atom->getChiralTag() != Atom::CHI_UNSPECIFIED) {
|
|
continue;
|
|
}
|
|
atom->setChiralTag(Atom::CHI_UNSPECIFIED);
|
|
// additional reasons to skip the atom:
|
|
auto nzDegree = Chirality::detail::getAtomNonzeroDegree(atom);
|
|
auto tnzDegree = nzDegree + atom->getTotalNumHs();
|
|
if (nzDegree < 3 || tnzDegree > 6) {
|
|
// not enough explicit neighbors or too many total neighbors
|
|
continue;
|
|
}
|
|
if (allowNontetrahedralStereo &&
|
|
assignNontetrahedralChiralTypeFrom3D(mol, conf, atom)) {
|
|
continue;
|
|
}
|
|
/* We're only doing tetrahedral cases here */
|
|
if (tnzDegree > 4) {
|
|
continue;
|
|
}
|
|
int anum = atom->getAtomicNum();
|
|
if (anum != 16 && anum != 34 && // S or Se are special
|
|
// (just using the InChI list for now)
|
|
tnzDegree != 4 // not enough total neighbors
|
|
) {
|
|
continue;
|
|
}
|
|
|
|
const auto &p0 = conf.getAtomPos(atom->getIdx());
|
|
const RDGeom::Point3D *nbrs[3];
|
|
unsigned int nbrIdx = 0;
|
|
int hasWigglyBond = 0;
|
|
for (const auto bond : mol.atomBonds(atom)) {
|
|
hasWigglyBond = isWigglyBond(bond, atom);
|
|
if (hasWigglyBond) {
|
|
break;
|
|
}
|
|
if (!Chirality::detail::bondAffectsAtomChirality(bond, atom)) {
|
|
continue;
|
|
}
|
|
nbrs[nbrIdx++] = &conf.getAtomPos(bond->getOtherAtomIdx(atom->getIdx()));
|
|
if (nbrIdx == 3) {
|
|
break;
|
|
}
|
|
}
|
|
if (hasWigglyBond) {
|
|
continue;
|
|
}
|
|
auto v1 = *nbrs[0] - p0;
|
|
auto v2 = *nbrs[1] - p0;
|
|
auto v3 = *nbrs[2] - p0;
|
|
|
|
double chiralVol = v1.dotProduct(v2.crossProduct(v3));
|
|
if (chiralVol < -ZERO_VOLUME_TOL) {
|
|
atom->setChiralTag(Atom::CHI_TETRAHEDRAL_CW);
|
|
} else if (chiralVol > ZERO_VOLUME_TOL) {
|
|
atom->setChiralTag(Atom::CHI_TETRAHEDRAL_CCW);
|
|
} else {
|
|
atom->setChiralTag(Atom::CHI_UNSPECIFIED);
|
|
}
|
|
}
|
|
}
|
|
|
|
void assignChiralTypesFromMolParity(ROMol &mol, bool replaceExistingTags) {
|
|
static const std::vector<Atom::ChiralType> chiralTypeVect{
|
|
Atom::CHI_TETRAHEDRAL_CW, Atom::CHI_TETRAHEDRAL_CCW};
|
|
// if the molecule already has stereochemistry
|
|
// perceived, remove the flags that indicate
|
|
// this... what we're about to do will require
|
|
// that we go again.
|
|
if (mol.hasProp(common_properties::_StereochemDone)) {
|
|
mol.clearProp(common_properties::_StereochemDone);
|
|
}
|
|
// Atom-based parity
|
|
// Number the atoms surrounding the stereo center with 1, 2, 3, and 4
|
|
// in order of increasing atom number (position in the atom block)
|
|
// (an implicit hydrogen should be considered the highest numbered atom).
|
|
// View the center from a position such that the bond connecting the
|
|
// highest-numbered atom (4) projects behind the plane formed by
|
|
// atoms 1, 2, and 3.
|
|
//
|
|
// Parity 1 (CW) Parity 2 (CCW)
|
|
// 3 1 3 2
|
|
// \ / \ /
|
|
// | |
|
|
// 2 1
|
|
//
|
|
for (auto atom : mol.atoms()) {
|
|
// if we aren't replacing existing tags and the atom is already tagged,
|
|
// punt:
|
|
if (!replaceExistingTags && atom->getChiralTag() != Atom::CHI_UNSPECIFIED) {
|
|
continue;
|
|
}
|
|
int parity = 0;
|
|
atom->getPropIfPresent(common_properties::molParity, parity);
|
|
if (parity <= 0 || parity > 2 || atom->getDegree() < 3) {
|
|
atom->setChiralTag(Atom::CHI_UNSPECIFIED);
|
|
continue;
|
|
}
|
|
// if we are here, parity was 1 (CW) or 2 (CCW)
|
|
// now we set parity 0 to be CW and 1 to be CCW
|
|
--parity;
|
|
RDKit::ROMol::OBOND_ITER_PAIR nbrBonds = mol.getAtomBonds(atom);
|
|
INT_LIST nbrBondIdxList;
|
|
std::transform(
|
|
nbrBonds.first, nbrBonds.second, std::back_inserter(nbrBondIdxList),
|
|
[&mol](const ROMol::edge_descriptor &e) { return mol[e]->getIdx(); });
|
|
unsigned int atomIdx = atom->getIdx();
|
|
nbrBondIdxList.sort([&mol, atomIdx](const int ai, const int bi) {
|
|
return (mol.getBondWithIdx(ai)->getOtherAtomIdx(atomIdx) <
|
|
mol.getBondWithIdx(bi)->getOtherAtomIdx(atomIdx));
|
|
});
|
|
int nSwaps = atom->getPerturbationOrder(nbrBondIdxList);
|
|
if (nSwaps % 2) {
|
|
parity = 1 - parity;
|
|
}
|
|
atom->setChiralTag(chiralTypeVect[parity]);
|
|
if (atom->getImplicitValence() == -1) {
|
|
atom->calcExplicitValence(false);
|
|
atom->calcImplicitValence(false);
|
|
}
|
|
// within the RD representation, if a three-coordinate atom
|
|
// is chiral and has an implicit H, that H needs to be made explicit:
|
|
if (atom->getDegree() == 3 && !atom->getNumExplicitHs() &&
|
|
atom->getNumImplicitHs() == 1) {
|
|
atom->setNumExplicitHs(1);
|
|
// recalculated number of implicit Hs:
|
|
atom->updatePropertyCache();
|
|
}
|
|
}
|
|
}
|
|
|
|
constexpr const char *isStereoAny = "_isStereoAny";
|
|
|
|
void setDoubleBondNeighborDirections(ROMol &mol, const Conformer *conf) {
|
|
// used to store the number of single bonds a given
|
|
// single bond is adjacent to
|
|
std::vector<unsigned int> singleBondCounts(mol.getNumBonds(), 0);
|
|
std::vector<Bond *> bondsInPlay;
|
|
// keeps track of which single bonds are adjacent to each double bond:
|
|
VECT_INT_VECT dblBondNbrs(mol.getNumBonds());
|
|
// keeps track of which double bonds are adjacent to each single bond:
|
|
VECT_INT_VECT singleBondNbrs(mol.getNumBonds());
|
|
// keeps track of which single bonds need a dir set and which double bonds
|
|
// need to have their neighbors' dirs set
|
|
boost::dynamic_bitset<> needsDir(mol.getNumBonds());
|
|
|
|
// find double bonds that should be considered for
|
|
// stereochemistry
|
|
// NOTE that we are explicitly excluding double bonds in rings
|
|
// with this test.
|
|
bool resetRings = false;
|
|
if (!mol.getRingInfo()->isInitialized()) {
|
|
resetRings = true;
|
|
MolOps::fastFindRings(mol);
|
|
}
|
|
|
|
for (auto bond : mol.bonds()) {
|
|
if (isBondCandidateForStereo(bond)) {
|
|
bool isCandidate = true;
|
|
for (const auto bondAtom : {bond->getBeginAtom(), bond->getEndAtom()}) {
|
|
for (const auto nbrBond : mol.atomBonds(bondAtom)) {
|
|
if (nbrBond->getBondType() == Bond::SINGLE ||
|
|
nbrBond->getBondType() == Bond::AROMATIC) {
|
|
singleBondCounts[nbrBond->getIdx()] += 1;
|
|
auto nbrDir = nbrBond->getBondDir();
|
|
int hasUnknownStereo = 0;
|
|
if (nbrBond->getBeginAtom() == bondAtom &&
|
|
nbrDir == Bond::BondDir::UNKNOWN &&
|
|
nbrBond->getPropIfPresent(common_properties::_UnknownStereo,
|
|
hasUnknownStereo) &&
|
|
hasUnknownStereo) {
|
|
// if there's a wiggly bond starting here, then we're not a
|
|
// candidate for stereo
|
|
isCandidate = false;
|
|
} else {
|
|
if (nbrDir == Bond::BondDir::NONE ||
|
|
nbrDir == Bond::BondDir::ENDDOWNRIGHT ||
|
|
nbrDir == Bond::BondDir::ENDUPRIGHT) {
|
|
needsDir[nbrBond->getIdx()] = 1;
|
|
}
|
|
needsDir[bond->getIdx()] = 1;
|
|
dblBondNbrs[bond->getIdx()].push_back(nbrBond->getIdx());
|
|
// the search may seem inefficient, but these vectors are going to
|
|
// be at most 2 long (with very few exceptions). It's just not
|
|
// worth using a different data structure
|
|
if (std::find(singleBondNbrs[nbrBond->getIdx()].begin(),
|
|
singleBondNbrs[nbrBond->getIdx()].end(),
|
|
bond->getIdx()) ==
|
|
singleBondNbrs[nbrBond->getIdx()].end()) {
|
|
singleBondNbrs[nbrBond->getIdx()].push_back(bond->getIdx());
|
|
}
|
|
}
|
|
}
|
|
if (!isCandidate) {
|
|
break;
|
|
}
|
|
}
|
|
if (!isCandidate) {
|
|
break;
|
|
}
|
|
}
|
|
if (isCandidate) {
|
|
bondsInPlay.push_back(bond);
|
|
}
|
|
}
|
|
}
|
|
|
|
if (!bondsInPlay.size()) {
|
|
if (resetRings) {
|
|
mol.getRingInfo()->reset();
|
|
}
|
|
return;
|
|
}
|
|
|
|
// order the double bonds based on the singleBondCounts of their neighbors:
|
|
std::vector<std::pair<unsigned int, Bond *>> orderedBondsInPlay;
|
|
for (auto dblBond : bondsInPlay) {
|
|
unsigned int countHere =
|
|
std::accumulate(dblBondNbrs[dblBond->getIdx()].begin(),
|
|
dblBondNbrs[dblBond->getIdx()].end(), 0);
|
|
// and favor double bonds that are *not* in rings. The combination of
|
|
// using the sum above (instead of the max) and this ring-membershipt test
|
|
// seem to fix sf.net issue 3009836
|
|
if (!(mol.getRingInfo()->numBondRings(dblBond->getIdx()))) {
|
|
countHere *= 10;
|
|
}
|
|
orderedBondsInPlay.push_back(std::make_pair(countHere, dblBond));
|
|
}
|
|
std::sort(orderedBondsInPlay.begin(), orderedBondsInPlay.end());
|
|
|
|
// oof, now loop over the double bonds in that order and
|
|
// update their neighbor directionalities:
|
|
std::vector<std::pair<unsigned int, Bond *>>::reverse_iterator pairIter;
|
|
for (pairIter = orderedBondsInPlay.rbegin();
|
|
pairIter != orderedBondsInPlay.rend(); ++pairIter) {
|
|
// std::cerr << "RESET?: " << pairIter->second->getIdx() << " "
|
|
// << pairIter->second->getStereo() << std::endl;
|
|
updateDoubleBondNeighbors(mol, pairIter->second, conf, needsDir,
|
|
singleBondCounts, singleBondNbrs);
|
|
}
|
|
if (resetRings) {
|
|
mol.getRingInfo()->reset();
|
|
}
|
|
}
|
|
|
|
void detectBondStereochemistry(ROMol &mol, int confId) {
|
|
if (!mol.getNumConformers()) {
|
|
return;
|
|
}
|
|
const Conformer &conf = mol.getConformer(confId);
|
|
setDoubleBondNeighborDirections(mol, &conf);
|
|
for (auto bond : mol.bonds()) {
|
|
if (bond->hasProp(isStereoAny)) {
|
|
bond->setStereo(Bond::BondStereo::STEREOANY);
|
|
bond->clearProp(isStereoAny);
|
|
}
|
|
}
|
|
}
|
|
|
|
void clearSingleBondDirFlags(ROMol &mol) {
|
|
for (auto bond : mol.bonds()) {
|
|
if (bond->getBondType() == Bond::SINGLE) {
|
|
if (bond->getBondDir() == Bond::UNKNOWN) {
|
|
bond->setProp(common_properties::_UnknownStereo, 1);
|
|
}
|
|
bond->setBondDir(Bond::NONE);
|
|
}
|
|
}
|
|
}
|
|
|
|
void setBondStereoFromDirections(ROMol &mol) {
|
|
for (Bond *bond : mol.bonds()) {
|
|
if (bond->getBondType() == Bond::DOUBLE) {
|
|
const Atom *stereoBondBeginAtom = bond->getBeginAtom();
|
|
const Atom *stereoBondEndAtom = bond->getEndAtom();
|
|
|
|
const Bond *directedBondAtBegin =
|
|
Chirality::getNeighboringDirectedBond(mol, stereoBondBeginAtom);
|
|
const Bond *directedBondAtEnd =
|
|
Chirality::getNeighboringDirectedBond(mol, stereoBondEndAtom);
|
|
|
|
if (directedBondAtBegin != nullptr && directedBondAtEnd != nullptr) {
|
|
unsigned beginSideStereoAtom =
|
|
directedBondAtBegin->getOtherAtomIdx(stereoBondBeginAtom->getIdx());
|
|
unsigned endSideStereoAtom =
|
|
directedBondAtEnd->getOtherAtomIdx(stereoBondEndAtom->getIdx());
|
|
|
|
bond->setStereoAtoms(beginSideStereoAtom, endSideStereoAtom);
|
|
|
|
auto beginSideBondDirection = directedBondAtBegin->getBondDir();
|
|
if (directedBondAtBegin->getBeginAtom() == stereoBondBeginAtom) {
|
|
beginSideBondDirection = getOppositeBondDir(beginSideBondDirection);
|
|
}
|
|
|
|
auto endSideBondDirection = directedBondAtEnd->getBondDir();
|
|
if (directedBondAtEnd->getEndAtom() == stereoBondEndAtom) {
|
|
endSideBondDirection = getOppositeBondDir(endSideBondDirection);
|
|
}
|
|
|
|
if (beginSideBondDirection == endSideBondDirection) {
|
|
bond->setStereo(Bond::STEREOTRANS);
|
|
} else {
|
|
bond->setStereo(Bond::STEREOCIS);
|
|
}
|
|
}
|
|
}
|
|
}
|
|
}
|
|
|
|
void assignStereochemistryFrom3D(ROMol &mol, int confId,
|
|
bool replaceExistingTags) {
|
|
if (!mol.getNumConformers() || !mol.getConformer(confId).is3D()) {
|
|
return;
|
|
}
|
|
if (mol.needsUpdatePropertyCache()) {
|
|
mol.updatePropertyCache(false);
|
|
}
|
|
|
|
detectBondStereochemistry(mol, confId);
|
|
assignChiralTypesFrom3D(mol, confId, replaceExistingTags);
|
|
bool force = true;
|
|
bool flagPossibleStereoCenters = true;
|
|
assignStereochemistry(mol, replaceExistingTags, force,
|
|
flagPossibleStereoCenters);
|
|
}
|
|
|
|
void assignChiralTypesFromBondDirs(ROMol &mol, const int confId,
|
|
const bool replaceExistingTags) {
|
|
if (!mol.getNumConformers()) {
|
|
return;
|
|
}
|
|
auto conf = mol.getConformer(confId);
|
|
boost::dynamic_bitset<> atomsSet(mol.getNumAtoms(), 0);
|
|
for (auto &bond : mol.bonds()) {
|
|
const Bond::BondDir dir = bond->getBondDir();
|
|
Atom *atom = bond->getBeginAtom();
|
|
if (dir == Bond::UNKNOWN) {
|
|
if (atomsSet[atom->getIdx()] || replaceExistingTags) {
|
|
atom->setChiralTag(Atom::CHI_UNSPECIFIED);
|
|
atomsSet.set(atom->getIdx());
|
|
}
|
|
} else {
|
|
// the bond is marked as chiral:
|
|
if (dir == Bond::BEGINWEDGE || dir == Bond::BEGINDASH) {
|
|
if (atomsSet[atom->getIdx()] ||
|
|
(!replaceExistingTags &&
|
|
atom->getChiralTag() != Atom::CHI_UNSPECIFIED)) {
|
|
continue;
|
|
}
|
|
if (atom->getImplicitValence() == -1) {
|
|
atom->calcExplicitValence(false);
|
|
atom->calcImplicitValence(false);
|
|
}
|
|
Atom::ChiralType code =
|
|
Chirality::atomChiralTypeFromBondDirPseudo3D(mol, bond, &conf)
|
|
.value_or(Atom::ChiralType::CHI_UNSPECIFIED);
|
|
if (code != Atom::ChiralType::CHI_UNSPECIFIED) {
|
|
atomsSet.set(atom->getIdx());
|
|
// std::cerr << "atom " << atom->getIdx() << " code " << code
|
|
// << " from bond " << bond->getIdx() << std::endl;
|
|
}
|
|
atom->setChiralTag(code);
|
|
|
|
// within the RD representation, if a three-coordinate atom
|
|
// is chiral and has an implicit H, that H needs to be made explicit:
|
|
if (atom->getDegree() == 3 && !atom->getNumExplicitHs() &&
|
|
atom->getNumImplicitHs() == 1) {
|
|
atom->setNumExplicitHs(1);
|
|
// recalculated number of implicit Hs:
|
|
atom->updatePropertyCache();
|
|
}
|
|
}
|
|
}
|
|
}
|
|
}
|
|
|
|
void removeStereochemistry(ROMol &mol) {
|
|
if (mol.hasProp(common_properties::_StereochemDone)) {
|
|
mol.clearProp(common_properties::_StereochemDone);
|
|
}
|
|
for (auto atom : mol.atoms()) {
|
|
atom->setChiralTag(Atom::CHI_UNSPECIFIED);
|
|
if (atom->hasProp(common_properties::_CIPCode)) {
|
|
atom->clearProp(common_properties::_CIPCode);
|
|
}
|
|
if (atom->hasProp(common_properties::_CIPRank)) {
|
|
atom->clearProp(common_properties::_CIPRank);
|
|
}
|
|
}
|
|
for (auto bond : mol.bonds()) {
|
|
if (bond->getBondType() == Bond::DOUBLE) {
|
|
bond->setStereo(Bond::BondStereo::STEREONONE);
|
|
bond->getStereoAtoms().clear();
|
|
bond->setBondDir(Bond::BondDir::NONE);
|
|
} else if (bond->getBondType() == Bond::SINGLE) {
|
|
bond->setBondDir(Bond::BondDir::NONE);
|
|
}
|
|
}
|
|
std::vector<StereoGroup> sgs;
|
|
static_cast<RWMol &>(mol).setStereoGroups(std::move(sgs));
|
|
}
|
|
|
|
} // end of namespace MolOps
|
|
} // namespace RDKit
|