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db025bd6b0b366abbf653600a4ca2730764e61d8
rdkit/Code/GraphMol/Chirality.cpp
Ricardo Rodriguez db025bd6b0 make sorting more consistent (#9239)
2026-04-16 05:05:14 +02:00

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//
// Copyright (C) 2004-2024 Greg Landrum and other RDKit contributors
//
// @@ All Rights Reserved @@
// This file is part of the RDKit.
// The contents are covered by the terms of the BSD license
// which is included in the file license.txt, found at the root
// of the RDKit source tree.
//
#include "Chirality.h"
#include <Geometry/point.h>
#include <GraphMol/QueryOps.h>
#include <GraphMol/RDKitBase.h>
#include <RDGeneral/Ranking.h>
#include <GraphMol/new_canon.h>
#include <GraphMol/Atropisomers.h>
#include <RDGeneral/Invariant.h>
#include <RDGeneral/RDLog.h>
#include <RDGeneral/types.h>
#include <RDGeneral/utils.h>
#include <boost/dynamic_bitset.hpp>
#include <boost/algorithm/string.hpp>
#include <algorithm>
#include <cstdlib>
#include <optional>
#include <ranges>
#include <set>
#include <sstream>
#include <utility>
// #define VERBOSE_CANON 1
namespace RDKit {
namespace {
bool shouldDetectDoubleBondStereo(const Bond *bond) {
const RingInfo *ri = bond->getOwningMol().getRingInfo();
return (!ri->numBondRings(bond->getIdx()) ||
ri->minBondRingSize(bond->getIdx()) >=
Chirality::minRingSizeForDoubleBondStereo);
}
bool getValFromEnvironment(const char *var, bool defVal) {
auto evar = std::getenv(var);
if (evar != nullptr) {
if (!strcmp(evar, "0")) {
return false;
} else {
return true;
}
}
return defVal;
}
bool is_regular_h(const Atom &atom) {
return atom.getAtomicNum() == 1 && atom.getIsotope() == 0;
}
Bond::BondDir getOppositeBondDir(Bond::BondDir dir) {
PRECONDITION(dir == Bond::ENDDOWNRIGHT || dir == Bond::ENDUPRIGHT,
"bad bond direction");
switch (dir) {
case Bond::ENDDOWNRIGHT:
return Bond::ENDUPRIGHT;
case Bond::ENDUPRIGHT:
return Bond::ENDDOWNRIGHT;
default:
return Bond::NONE;
}
}
void setBondDirRelativeToAtom(Bond *bond, Atom *atom, Bond::BondDir dir,
bool reverse, boost::dynamic_bitset<> &) {
PRECONDITION(bond, "bad bond");
PRECONDITION(atom, "bad atom");
PRECONDITION(dir == Bond::ENDUPRIGHT || dir == Bond::ENDDOWNRIGHT, "bad dir");
PRECONDITION(atom == bond->getBeginAtom() || atom == bond->getEndAtom(),
"atom doesn't belong to bond");
if (bond->getBeginAtom() != atom) {
reverse = !reverse;
}
if (reverse) {
dir = (dir == Bond::ENDUPRIGHT ? Bond::ENDDOWNRIGHT : Bond::ENDUPRIGHT);
}
// to ensure maximum compatibility, even when a bond has unknown stereo (set
// explicitly and recorded in _UnknownStereo property), I will still let a
// direction to be computed. You must check the _UnknownStereo property to
// make sure whether this bond is explicitly set to have no direction info.
// This makes sense because the direction info are all derived from
// coordinates, the _UnknownStereo property is like extra metadata to be
// used with the direction info.
bond->setBondDir(dir);
}
bool isLinearArrangement(const RDGeom::Point3D &v1, const RDGeom::Point3D &v2) {
double lsq = v1.lengthSq() * v2.lengthSq();
// treat zero length vectors as linear
if (lsq < 1.0e-6) {
return true;
}
double dotProd = v1.dotProduct(v2);
double cos178 =
-0.999388; // == cos(M_PI-0.035), corresponds to a tolerance of 2 degrees
return dotProd < cos178 * sqrt(lsq);
}
void controllingBondFromAtom(const ROMol &mol,
const boost::dynamic_bitset<> &needsDir,
const std::vector<unsigned int> &singleBondCounts,
const Bond *dblBond, const Atom *atom, Bond *&bond,
Bond *&obond, bool &squiggleBondSeen,
bool &doubleBondSeen) {
bond = nullptr;
obond = nullptr;
for (const auto tBond : mol.atomBonds(atom)) {
if (tBond == dblBond) {
continue;
}
if ((tBond->getBondType() == Bond::SINGLE ||
tBond->getBondType() == Bond::AROMATIC) &&
(tBond->getBondDir() == Bond::BondDir::NONE ||
tBond->getBondDir() == Bond::BondDir::ENDDOWNRIGHT ||
tBond->getBondDir() == Bond::BondDir::ENDUPRIGHT)) {
// prefer bonds that already have their directionality set
// or that are adjacent to more double bonds:
if (!bond) {
bond = tBond;
} else if (needsDir[tBond->getIdx()]) {
if (singleBondCounts[tBond->getIdx()] >
singleBondCounts[bond->getIdx()]) {
obond = bond;
bond = tBond;
} else {
obond = tBond;
}
} else {
obond = bond;
bond = tBond;
}
} else if (tBond->getBondType() == Bond::DOUBLE) {
doubleBondSeen = true;
}
int explicit_unknown_stereo;
if ((tBond->getBondType() == Bond::SINGLE ||
tBond->getBondType() == Bond::AROMATIC) &&
(tBond->getBondDir() == Bond::UNKNOWN ||
((tBond->getPropIfPresent<int>(common_properties::_UnknownStereo,
explicit_unknown_stereo) &&
explicit_unknown_stereo)))) {
squiggleBondSeen = true;
break;
}
}
}
void updateDoubleBondNeighbors(ROMol &mol, Bond *dblBond, const Conformer *conf,
boost::dynamic_bitset<> &needsDir,
std::vector<unsigned int> &singleBondCounts,
const VECT_INT_VECT &singleBondNbrs) {
// we want to deal only with double bonds:
PRECONDITION(dblBond, "bad bond");
PRECONDITION(dblBond->getBondType() == Bond::DOUBLE, "not a double bond");
if (!needsDir[dblBond->getIdx()]) {
return;
}
needsDir.set(dblBond->getIdx(), 0);
std::vector<Bond *> followupBonds;
Bond *bond1 = nullptr, *obond1 = nullptr;
bool squiggleBondSeen = false;
bool doubleBondSeen = false;
controllingBondFromAtom(mol, needsDir, singleBondCounts, dblBond,
dblBond->getBeginAtom(), bond1, obond1,
squiggleBondSeen, doubleBondSeen);
// Don't do any direction setting if we've seen a squiggle bond, but do mark
// the double bond as a crossed bond and return
if (squiggleBondSeen) {
Chirality::detail::setStereoForBond(mol, dblBond, Bond::STEREOANY);
return;
}
if (!bond1) {
return;
}
Bond *bond2 = nullptr, *obond2 = nullptr;
controllingBondFromAtom(mol, needsDir, singleBondCounts, dblBond,
dblBond->getEndAtom(), bond2, obond2,
squiggleBondSeen, doubleBondSeen);
// Don't do any direction setting if we've seen a squiggle bond, but do mark
// the double bond as a crossed bond and return
if (squiggleBondSeen) {
Chirality::detail::setStereoForBond(mol, dblBond, Bond::STEREOANY);
return;
}
if (!bond2) {
return;
}
CHECK_INVARIANT(bond1 && bond2, "no bonds found");
bool sameTorsionDir = false;
if (conf) {
RDGeom::Point3D beginP = conf->getAtomPos(dblBond->getBeginAtomIdx());
RDGeom::Point3D endP = conf->getAtomPos(dblBond->getEndAtomIdx());
RDGeom::Point3D bond1P =
conf->getAtomPos(bond1->getOtherAtomIdx(dblBond->getBeginAtomIdx()));
RDGeom::Point3D bond2P =
conf->getAtomPos(bond2->getOtherAtomIdx(dblBond->getEndAtomIdx()));
// check for a linear arrangement of atoms on either end:
bool linear = false;
RDGeom::Point3D p1;
RDGeom::Point3D p2;
p1 = bond1P - beginP;
p2 = endP - beginP;
if (isLinearArrangement(p1, p2)) {
if (!obond1) {
linear = true;
} else {
// one of the bonds was linear; what about the other one?
Bond *tBond = bond1;
bond1 = obond1;
obond1 = tBond;
bond1P = conf->getAtomPos(
bond1->getOtherAtomIdx(dblBond->getBeginAtomIdx()));
p1 = bond1P - beginP;
if (isLinearArrangement(p1, p2)) {
linear = true;
}
}
}
if (!linear) {
p1 = bond2P - endP;
p2 = beginP - endP;
if (isLinearArrangement(p1, p2)) {
if (!obond2) {
linear = true;
} else {
Bond *tBond = bond2;
bond2 = obond2;
obond2 = tBond;
bond2P = conf->getAtomPos(
bond2->getOtherAtomIdx(dblBond->getEndAtomIdx()));
p1 = bond2P - beginP;
if (isLinearArrangement(p1, p2)) {
linear = true;
}
}
}
}
if (linear) {
Chirality::detail::setStereoForBond(mol, dblBond, Bond::STEREOANY);
return;
}
double ang = RDGeom::computeDihedralAngle(bond1P, beginP, endP, bond2P);
sameTorsionDir = ang >= M_PI / 2;
// std::cerr << " angle: " << ang << " sameTorsionDir: " << sameTorsionDir
// << "\n";
} else {
if (dblBond->getStereo() == Bond::STEREOCIS ||
dblBond->getStereo() == Bond::STEREOZ) {
sameTorsionDir = false;
} else if (dblBond->getStereo() == Bond::STEREOTRANS ||
dblBond->getStereo() == Bond::STEREOE) {
sameTorsionDir = true;
} else {
return;
}
// if bond1 or bond2 are not to the stereo-controlling atoms, flip
// our expections of the torsion dir
int bond1AtomIdx = bond1->getOtherAtomIdx(dblBond->getBeginAtomIdx());
if (bond1AtomIdx != dblBond->getStereoAtoms()[0] &&
bond1AtomIdx != dblBond->getStereoAtoms()[1]) {
sameTorsionDir = !sameTorsionDir;
}
int bond2AtomIdx = bond2->getOtherAtomIdx(dblBond->getEndAtomIdx());
if (bond2AtomIdx != dblBond->getStereoAtoms()[0] &&
bond2AtomIdx != dblBond->getStereoAtoms()[1]) {
sameTorsionDir = !sameTorsionDir;
}
}
/*
Time for some clarificatory text, because this gets really
confusing really fast.
The dihedral angle analysis above is based on viewing things
with an atom order as follows:
1
\
2 = 3
\
4
so dihedrals > 90 correspond to sameDir=true
however, the stereochemistry representation is
based on something more like this:
2
\
1 = 3
\
4
(i.e. we consider the direction-setting single bonds to be
starting at the double-bonded atom)
*/
bool reverseBondDir = sameTorsionDir;
Atom *atom1 = dblBond->getBeginAtom(), *atom2 = dblBond->getEndAtom();
if (needsDir[bond1->getIdx()]) {
for (auto bidx : singleBondNbrs[bond1->getIdx()]) {
// std::cerr << " neighbor from: " << bond1->getIdx() << " " << bidx
// << ": " << needsDir[bidx] << std::endl;
if (needsDir[bidx]) {
followupBonds.push_back(mol.getBondWithIdx(bidx));
}
}
}
if (needsDir[bond2->getIdx()]) {
for (auto bidx : singleBondNbrs[bond2->getIdx()]) {
// std::cerr << " neighbor from: " << bond2->getIdx() << " " << bidx
// << ": " << needsDir[bidx] << std::endl;
if (needsDir[bidx]) {
followupBonds.push_back(mol.getBondWithIdx(bidx));
}
}
}
if (!needsDir[bond1->getIdx()]) {
if (!needsDir[bond2->getIdx()]) {
// check that we agree
} else {
if (bond1->getBeginAtom() != atom1) {
reverseBondDir = !reverseBondDir;
}
setBondDirRelativeToAtom(bond2, atom2, bond1->getBondDir(),
reverseBondDir, needsDir);
}
} else if (!needsDir[bond2->getIdx()]) {
if (bond2->getBeginAtom() != atom2) {
reverseBondDir = !reverseBondDir;
}
setBondDirRelativeToAtom(bond1, atom1, bond2->getBondDir(), reverseBondDir,
needsDir);
} else {
setBondDirRelativeToAtom(bond1, atom1, Bond::ENDDOWNRIGHT, false, needsDir);
setBondDirRelativeToAtom(bond2, atom2, Bond::ENDDOWNRIGHT, reverseBondDir,
needsDir);
}
needsDir[bond1->getIdx()] = 0;
needsDir[bond2->getIdx()] = 0;
if (obond1 && needsDir[obond1->getIdx()]) {
setBondDirRelativeToAtom(obond1, atom1, bond1->getBondDir(),
bond1->getBeginAtom() == atom1, needsDir);
needsDir[obond1->getIdx()] = 0;
}
if (obond2 && needsDir[obond2->getIdx()]) {
setBondDirRelativeToAtom(obond2, atom2, bond2->getBondDir(),
bond2->getBeginAtom() == atom2, needsDir);
needsDir[obond2->getIdx()] = 0;
}
for (Bond *oDblBond : followupBonds) {
updateDoubleBondNeighbors(mol, oDblBond, conf, needsDir, singleBondCounts,
singleBondNbrs);
}
}
bool isBondCandidateForStereo(const Bond *bond) {
PRECONDITION(bond, "no bond");
return bond->getBondType() == Bond::DOUBLE &&
bond->getStereo() != Bond::STEREOANY &&
bond->getBondDir() != Bond::EITHERDOUBLE &&
bond->getBeginAtom()->getDegree() > 1u &&
bond->getEndAtom()->getDegree() > 1u &&
shouldDetectDoubleBondStereo(bond);
}
const Atom *findHighestCIPNeighbor(const Atom *atom, const Atom *skipAtom) {
PRECONDITION(atom, "bad atom");
unsigned bestCipRank = 0;
const Atom *bestCipRankedAtom = nullptr;
const auto &mol = atom->getOwningMol();
for (const auto neighbor : mol.atomNeighbors(atom)) {
if (neighbor == skipAtom) {
continue;
}
unsigned cip = 0;
if (!neighbor->getPropIfPresent(common_properties::_CIPRank, cip)) {
// If at least one of the atoms doesn't have a CIP rank, the highest rank
// does not make sense, so return a nullptr.
return nullptr;
} else if (cip > bestCipRank || bestCipRankedAtom == nullptr) {
bestCipRank = cip;
bestCipRankedAtom = neighbor;
} else if (cip == bestCipRank) {
// This also doesn't make sense if there is a tie (if that's possible).
// We still keep the best CIP rank in case something better comes around
// (also not sure if that's possible).
BOOST_LOG(rdWarningLog)
<< "Warning: duplicate CIP ranks found in findHighestCIPNeighbor()"
<< std::endl;
bestCipRankedAtom = nullptr;
}
}
return bestCipRankedAtom;
}
} // namespace
namespace Chirality {
std::optional<Atom::ChiralType> atomChiralTypeFromBondDirPseudo3D(
const ROMol &mol, const Bond *bond, const Conformer *conf) {
PRECONDITION(bond, "no bond");
PRECONDITION(conf, "no conformer");
auto bondDir = bond->getBondDir();
PRECONDITION(bondDir == Bond::BEGINWEDGE || bondDir == Bond::BEGINDASH,
"bad bond direction");
constexpr double coordZeroTol = 1e-4;
constexpr double zeroTol = 1e-3;
constexpr double tShapeTol =
0.00031; // used to recognize T-shaped arrangements
// corresponds to an angle between the two vectors of just under 178 degrees
// degree
constexpr double pseudo3DOffset = 0.1; // z-displacement for wedged bonds
constexpr double volumeTolerance =
0.00174; // used to recognize zero chiral volume
// This is what we get for a T-shaped arrangement with just over 178 degrees
// 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());
// Github #7305: in some odd cases, we get conformers with
// weird scalings. In these, we need to scale the 3d offset
// or it might be irrelevant or dominate over the coordinates.
auto refLength = (centerLoc - refPt).length();
refPt.z =
bondDir == Bond::BondDir::BEGINWEDGE ? pseudo3DOffset : -pseudo3DOffset;
if (refLength) {
refPt.z *= refLength;
}
//----------------------------------------------------------
//
// collect indices and bond vectors of neighbors and track whether or
// not there's an H neighbor and if all bonds are single
//
// at the end of this process bond 0 is the input wedged bond
//
//----------------------------------------------------------
INT_VECT neighborBondIndices;
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 ||
nbrBond->getBondDir() == Bond::BondDir::BEGINDASH)) {
// scale the 3d offset based on the reference bond here too
tmpPt.z = nbrBond->getBondDir() == Bond::BondDir::BEGINWEDGE
? pseudo3DOffset
: -pseudo3DOffset;
if (refLength) {
tmpPt.z *= refLength;
}
} else {
tmpPt.z = 0;
}
// check for overly short bonds. Note that we're doing this check *after*
// adjusting the z coordinate.
// We want to allow atoms to overlap in x-y space if they are connected
// via a wedged bond.
if ((centerLoc - tmpPt).lengthSq() < zeroTol) {
BOOST_LOG(rdWarningLog)
<< "Warning: ambiguous stereochemistry - zero-length (or near zero-length) bond - at atom "
<< atom->getIdx() << " ignored." << std::endl;
return std::nullopt;
}
}
++nbrIdx;
if (nbrBond->getBondType() != Bond::SINGLE) {
allSingle = false;
}
bondVects.push_back(centerLoc.directionVector(tmpPt));
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 bonds to the atom.
// (we can implicitly add a single H to 3 coordinate atoms).
//
//----------------------------------------------------------
if (nNbrs < 3 || nNbrs > 4) {
return std::nullopt;
}
//----------------------------------------------------------
// Check for neighbor atoms which overlap
//----------------------------------------------------------
for (auto i = 0u; i < nNbrs; ++i) {
for (auto j = 0u; j < i; ++j) {
if ((bondVects[i] - bondVects[j]).lengthSq() < zeroTol) {
BOOST_LOG(rdWarningLog)
<< "Warning: ambiguous stereochemistry - overlapping neighbors - at atom "
<< atom->getIdx() << " ignored" << std::endl;
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;
}
// check for the case that bonds 1 and 2 are co-linear but 1 and 0 are
// not:
if (nNbrs > 3 &&
bondVects[order[1]].crossProduct(bondVects[order[2]]).lengthSq() <
10 * zeroTol &&
bondVects[order[1]].crossProduct(bondVects[order[0]]).lengthSq() >
10 * zeroTol) {
bondVects[order[1]].z = bondVects[order[0]].z * -1;
// that bondVect is no longer normalized, but this hopefully won't break
// anything
}
//----------------------------------------------------------
//
// order the bonds so that the rotation order is:
// 0 - 1 - 2 for three coordinate
// or
// 0 - 1 - 2 - 3 for four coordinate
//
// this makes the rest of the code a lot simpler
//
//----------------------------------------------------------
// checks to see if the vectors 1 and 2 need to have their order
// relative to vector 0 swapped.
// we don't actually pass the vectors in, but use their cross products
// and dot products to vector 0 to figure out if they need to be swapped
#if defined(__clang__)
// Clang apparently doesn't need to capture the constexpr zeroTol, and complains
// about it being specified, but MSVC does need it, and removing it will break
// the build
#pragma GCC diagnostic push
#pragma GCC diagnostic ignored "-Wunused-lambda-capture"
#endif
auto needsSwap = [&zeroTol](const RDGeom::Point3D &cp01,
const RDGeom::Point3D &cp02, double dp01,
double dp02) -> bool {
if (fabs(dp01) - 1 > -zeroTol) {
if (cp02.z < 0) {
return true;
}
return false;
}
if (fabs(dp02) - 1 > -zeroTol) {
if (cp01.z < 0) {
return true;
}
}
if ((cp01.z * cp02.z) < -zeroTol) {
if (cp01.z < cp02.z) {
return true;
}
return false;
}
if (dp01 * dp02 < -zeroTol) {
if (dp01 < dp02) {
return true;
}
return false;
}
return fabs(dp01) > fabs(dp02);
};
#if defined(__clang__)
#pragma GCC diagnostic pop
#endif
if (nNbrs == 3) {
// this case is simple, we either need to swap vectors 1 and 2 or we
// don't:
auto cp01 = bondVects[order[0]].crossProduct(bondVects[order[1]]);
auto cp02 = bondVects[order[0]].crossProduct(bondVects[order[2]]);
auto dp01 = bondVects[order[0]].dotProduct(bondVects[order[1]]);
auto dp02 = bondVects[order[0]].dotProduct(bondVects[order[2]]);
if (needsSwap(cp01, cp02, dp01, dp02)) {
std::swap(order[1], order[2]);
prefactor *= -1;
}
} else if (nNbrs > 3) {
// here there are more permutations. Rather than hand-coding all of them
// we'll just sort bonds 1, 2, and 3 based on their cross- and dot-
// products to bond 0
std::vector<std::tuple<double, double, unsigned>> orderedBonds(3);
for (auto i = 1u; i < 4; ++i) {
auto cp0i = bondVects[order[0]].crossProduct(bondVects[order[i]]);
auto sgn = cp0i.z < -zeroTol ? -1 : 1;
auto dp0i = bondVects[order[0]].dotProduct(bondVects[order[i]]);
orderedBonds[i - 1] = std::make_tuple(sgn, sgn * dp0i, order[i]);
}
std::sort(orderedBonds.rbegin(), orderedBonds.rend());
// update the order array and figure out whether or not we've done a
// cyclic permutation
auto nChanged = 0;
for (auto i = 1u; i < 4; ++i) {
auto ni = std::get<2>(orderedBonds[i - 1]);
if (order[i] != ni) {
order[i] = ni;
++nChanged;
}
}
if (nChanged == 2) {
// this is always an acyclic permutation
prefactor *= -1;
}
}
// std::cerr<<"ORDER "<<neighborBondIndices[order[0]]<<"
// "<<neighborBondIndices[order[1]]<<" "<<neighborBondIndices[order[2]]<<"
// "<<neighborBondIndices[order[3]]<<std::endl;
// check for opposing bonds with opposite wedging
for (auto i = 0u; i < nNbrs; ++i) {
for (auto j = i + 1; j < nNbrs; ++j) {
if (bondVects[order[i]].z * bondVects[order[j]].z < -zeroTol) {
auto cp =
bondVects[order[i]].crossProduct(bondVects[order[j]]).lengthSq();
if (cp < 0.01) {
// exception to our rejection of these structures: in some horrible
// pseudo-3D drawings of things like sugars the ring substituents
// are drawn 180 degrees apart and with opposite wedging. Let that
// one pass.
if (nNbrs == 4 &&
fabs(bondVects[order[i]].dotProduct(bondVects[order[j]]) + 1) <
zeroTol) {
// this is allowed for neighboring bonds
if (j - i == 1 || (i == 0 && j == 3)) {
// std::cerr << " skip it " << std::endl;
bondVects[order[j]].z = 0.0;
continue;
}
}
BOOST_LOG(rdWarningLog)
<< "Warning: ambiguous stereochemistry - opposing bonds have opposite wedging - at atom "
<< atom->getIdx() << " ignored." << std::endl;
return std::nullopt;
}
}
}
}
// 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 < -coordZeroTol &&
fabs(bondVects[order[2]].z) < coordZeroTol) {
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 <
-coordZeroTol &&
fabs(bondVects[order[1]].z) < coordZeroTol) {
conflict = bondVects[order[1]].crossProduct(bondVects[order[0]]).z *
bondVects[order[1]].crossProduct(bondVects[order[2]]).z <
-coordZeroTol;
}
if (conflict) {
BOOST_LOG(rdWarningLog)
<< "Warning: conflicting stereochemistry - bond wedging contradiction - at atom "
<< atom->getIdx() << " ignored" << std::endl;
return std::nullopt;
}
}
// for the purposes of the cross products we ignore any pseudo-3D
// coordinates
auto bv1 = bondVects[order[1]];
bv1.z = 0;
auto bv2 = bondVects[order[2]];
bv2.z = 0;
auto crossp1 = bv1.crossProduct(bv2);
// catch linear arrangements
if (nNbrs == 3) {
if (crossp1.lengthSq() < tShapeTol) {
// in a linear relationship with three neighbors we assume that the
// two perpendicular bonds are wedged in the other direction from the
// one that was provided.
// that's this situation:
//
// 0
// | <- wedged up
// 1--C--2
//
// here we assume that bonds C-1 and C-2 are wedged down
//
// ST-1.2.12 of the IUPAC guidelines says that this form is wrong since
// it's for a "T-shaped" configuration instead of a tetrahedron, but it
// shows up fairly frequently, particularly with fused ring systems
bv1.z = -bondVects[order[0]].z;
bv2.z = -bondVects[order[0]].z;
crossp1 = bv1.crossProduct(bv2);
}
} else if (crossp1.lengthSq() < 10 * zeroTol) {
// if the other bond is flat:
if (fabs(bondVects[order[3]].z) < coordZeroTol) {
// By construction this is a neighboring bond, so make it the opposite
// wedging from us.
bondVects[order[3]].z = -1 * bondVects[order[0]].z;
// that bondVect is no longer normalized, but this hopefully won't break
// anything
}
}
vol = crossp1.dotProduct(bondVects[order[0]]);
if (nNbrs == 4) {
const auto dotp1 = bondVects[order[1]].dotProduct(bondVects[order[2]]);
// for the purposes of the cross products we ignore any pseudo-3D
// coordinates
auto bv3 = bondVects[order[3]];
bv3.z = 0;
const auto crossp2 = bv1.crossProduct(bv3);
const auto dotp2 = bondVects[order[1]].dotProduct(bondVects[order[3]]);
auto vol2 = crossp2.dotProduct(bondVects[order[0]]);
// detect the case where there's no chiral volume for the default
// evaluation
if (fabs(vol) < zeroTol) {
// and check the other evaluation:
if (fabs(vol2) < zeroTol) {
BOOST_LOG(rdWarningLog)
<< "Warning: ambiguous stereochemistry - no chiral volume - at atom "
<< atom->getIdx() << " ignored" << std::endl;
return std::nullopt;
}
vol = vol2;
prefactor *= -1;
} else if (vol * vol2 > 0 && fabs(vol2) > volumeTolerance &&
dotp1 < dotp2) {
// both volumes give the same answer, but in the second case the cross
// product is between two bonds with a better dot product
vol = vol2;
prefactor *= -1;
} else if (fabs(vol) < volumeTolerance && fabs(vol2) > volumeTolerance) {
// if the first volume is too small, but the second isn't, take the
// second
if (vol * vol2 < 0) {
prefactor *= -1;
}
vol = vol2;
}
}
vol *= prefactor;
// std::cerr << " final " << vol << std::endl;
// at this point we can assign our atomic stereo based on the sign of the
// chiral volume
if (vol > volumeTolerance) {
res = Atom::ChiralType::CHI_TETRAHEDRAL_CCW;
} else if (vol < -volumeTolerance) {
res = Atom::ChiralType::CHI_TETRAHEDRAL_CW;
} else {
BOOST_LOG(rdWarningLog)
<< "Warning: ambiguous stereochemistry - zero final chiral volume - at atom "
<< atom->getIdx() << " ignored" << std::endl;
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;
}
void setStereoForBond(ROMol &mol, Bond *bond, Bond::BondStereo stereo,
bool useCXSmilesOrdering) {
// NOTE: moved from parse_doublebond_stereo CXSmilesOps
// IF useCXSmilesOrdering is true, the cis/trans/unknown marker will be
// assigned relative to the lowest-numbered neighbor of each double bond atom.
// Otherwise it uses the lowest-numbered neighbor on the lower-numbered atom
// of the double bond and the highest-numbered neighbor on the higher-numbered
// atom
auto begAtom = bond->getBeginAtom();
auto endAtom = bond->getEndAtom();
if (begAtom->getIdx() > endAtom->getIdx()) {
std::swap(begAtom, endAtom);
}
if (begAtom->getDegree() > 1 && endAtom->getDegree() > 1) {
unsigned int begControl = mol.getNumAtoms();
for (auto nbr : mol.atomNeighbors(begAtom)) {
if (nbr == endAtom) {
continue;
}
begControl = std::min(nbr->getIdx(), begControl);
}
unsigned int endControl = useCXSmilesOrdering ? mol.getNumAtoms() : 0;
for (auto nbr : mol.atomNeighbors(endAtom)) {
if (nbr == begAtom) {
continue;
}
endControl = useCXSmilesOrdering ? std::min(nbr->getIdx(), endControl)
: std::max(nbr->getIdx(), endControl);
}
if (begAtom != bond->getBeginAtom()) {
std::swap(begControl, endControl);
}
bond->setStereoAtoms(begControl, endControl);
bond->setStereo(stereo);
mol.setProp("_needsDetectBondStereo", 1);
}
}
} // 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;
}
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;
}
}
//! Lightweight sortable wrapper that references a CIP entry and keeps track of
//! the current rank.
struct SortableCIPReference {
SortableCIPReference(CIP_ENTRY *cipRef, const int atomIdx)
: cip(cipRef), atomIdx(atomIdx) {
CHECK_INVARIANT(cip != nullptr, "null CIP entry");
}
SortableCIPReference(SortableCIPReference &&other) noexcept {
cip = other.cip;
atomIdx = other.atomIdx;
other.cip = nullptr;
currRank = other.currRank;
}
SortableCIPReference &operator=(SortableCIPReference &&other) noexcept {
if (this == &other) {
return *this;
}
cip = other.cip;
atomIdx = other.atomIdx;
other.cip = nullptr;
currRank = other.currRank;
return *this;
}
bool operator==(const SortableCIPReference &rhs) const {
PRECONDITION(cip != nullptr, "null CIP entry");
PRECONDITION(rhs.cip != nullptr, "null CIP entry");
return *cip == *rhs.cip;
}
bool operator<(const SortableCIPReference &rhs) const {
PRECONDITION(cip != nullptr, "null CIP entry");
PRECONDITION(rhs.cip != nullptr, "null CIP entry");
return *cip < *rhs.cip;
}
CIP_ENTRY *cip = nullptr;
int atomIdx = -1;
int currRank = -1;
};
//! Iterate over sorted entries, track tied regions and assign ranks.
//! \param sortedEntries CIP entries
//! \param res Pairs of start, end index of tied atoms
//! \param numIndependentEntries The number of unique ranks.
void findSegmentsToResort(std::vector<SortableCIPReference> &sortedEntries,
std::vector<std::pair<int, int>> &res,
unsigned int &numIndependentEntries) {
res.clear();
numIndependentEntries = rdcast<unsigned int>(sortedEntries.size());
SortableCIPReference *current = &sortedEntries.front();
int runningRank = 0;
current->currRank = runningRank;
bool inEqualSection = false;
for (size_t i = 1; i < sortedEntries.size(); i++) {
SortableCIPReference &entry = sortedEntries[i];
if (*current == entry) {
entry.currRank = runningRank;
numIndependentEntries--;
// Case where we need to open a section
if (!inEqualSection) {
inEqualSection = true;
auto &[firstIndex, _] = res.emplace_back();
// Go back to the first in this section, we only catch at first + 1
firstIndex = i - 1;
} else {
// Case where we are already in a section, nullop
}
} else {
// Case where we're closing an open section.
runningRank++;
entry.currRank = runningRank;
current = &entry;
if (inEqualSection) {
auto &[_, finalIndex] = res.back();
finalIndex = i;
inEqualSection = false;
}
}
}
// Handle currently open.
if (inEqualSection) {
auto &[_, finalIndex] = res.back();
finalIndex = sortedEntries.size() - 1;
}
}
struct PrecomputedBondFeatures {
//! Pairs of {atom index, counts}, strided by 8 for each atom.
std::vector<std::pair<std::uint8_t, int>> countsAndNeighborIndices;
//! Number of neighbors per atom.
std::vector<std::uint8_t> numNeighbors;
};
constexpr int kMaxBonds = 16;
//! Lookup neighbor indices and compute counts for each atom.
PrecomputedBondFeatures computeBondFeatures(const ROMol &mol) {
PrecomputedBondFeatures features;
const unsigned int numAtoms = mol.getNumAtoms();
features.countsAndNeighborIndices.resize(numAtoms * kMaxBonds);
features.numNeighbors.resize(numAtoms, 0);
for (size_t atomIdx = 0; atomIdx < numAtoms; atomIdx++) {
int indexOffset = atomIdx * kMaxBonds;
for (const auto bond : mol.atomBonds(mol[atomIdx])) {
const unsigned int nbrIdx = bond->getOtherAtomIdx(atomIdx);
features.numNeighbors[nbrIdx]++;
auto &[count, neighborIndex] =
features.countsAndNeighborIndices.at(indexOffset);
neighborIndex = 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) {
count += 1;
} else {
count += getTwiceBondType(*bond);
}
++indexOffset;
}
}
return features;
}
void recomputeRanks(const std::vector<SortableCIPReference> &sortedEntries,
std::vector<unsigned int> &ranks) {
for (size_t rank = 0; rank < ranks.size(); ++rank) {
const auto &cipEntry = sortedEntries[rank];
ranks[cipEntry.atomIdx] = cipEntry.currRank;
}
}
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);
}
std::vector<SortableCIPReference> sortableEntries;
sortableEntries.reserve(numAtoms);
for (size_t i = 0; i < cipEntries.size(); i++) {
sortableEntries.emplace_back(&cipEntries[i], i);
}
#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
for (unsigned int i = 0; i < numAtoms; i++) {
cipEntries[i].push_back(static_cast<int>(invars[i]));
}
unsigned int numRanks;
std::sort(sortableEntries.begin(), sortableEntries.end());
std::vector<std::pair<int, int>> needsSorting;
findSegmentsToResort(sortableEntries, needsSorting, numRanks);
recomputeRanks(sortableEntries, 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][0] = static_cast<int>(invars[i]);
} else {
cipEntries[i][0] = mol[i]->getAtomicNum();
cipEntries[i].push_back(static_cast<int>(ranks[i]));
}
}
// Based on above seeding, the rank will be set at index 1 or 2.
const int cipRankIndex = seedWithInvars ? 1 : 2;
// 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;
PrecomputedBondFeatures bondFeatures = computeBondFeatures(mol);
while (!needsSorting.empty() && numIts < maxIts &&
(lastNumRanks < 0 ||
static_cast<unsigned int>(lastNumRanks) < numRanks)) {
// ----------------------------------------------------
//
// for each atom, get a sorted list of its neighbors' ranks:
//
for (unsigned int index = 0; index < numAtoms; ++index) {
const unsigned int indexOffset = kMaxBonds * index;
const int numNeighbors = bondFeatures.numNeighbors[index];
auto *sortBegin = &bondFeatures.countsAndNeighborIndices[indexOffset];
auto *sortEnd = sortBegin + numNeighbors + 1;
// 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 (numNeighbors > 1) { // compare vs 1 for performance.
std::sort(sortBegin, sortEnd,
[&ranks](const std::pair<std::uint8_t, int> &countAndIdx1,
const std::pair<std::uint8_t, int> &countAndIdx2) {
return ranks[countAndIdx1.second] >
ranks[countAndIdx2.second];
});
}
auto &cipEntry = cipEntries[index];
for (auto *iter = sortBegin; iter != sortEnd; ++iter) {
const auto &[count, idx] = *iter;
cipEntry.insert(cipEntry.end(), count, ranks[idx] + 1);
}
// 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);
}
}
// ----------------------------------------------------
//
// sort the new ranks and update the list of active indices:
//
lastNumRanks = numRanks;
// Loop through previously tied atom sections and re-sort.
for (const auto &[firstIdx, lastIdx] : needsSorting) {
std::sort(sortableEntries.begin() + firstIdx,
sortableEntries.begin() + lastIdx + 1);
}
findSegmentsToResort(sortableEntries, needsSorting, numRanks);
// Map out of order rankings back to the absolute rankings vector.
recomputeRanks(sortableEntries, ranks);
// 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].resize(cipRankIndex + 1);
cipEntries[i][cipRankIndex] = ranks[i];
}
}
++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 (the ring neighbors
// will have the same rank)
// 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,
const std::vector<unsigned int> &atomRanks) {
PRECONDITION(atom, "bad atom");
bool res = false;
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->getTotalDegree() == 3 &&
!ringInfo->isAtomInRingOfSize(atom->getIdx(), 3) &&
!queryIsAtomBridgehead(atom)) {
return false;
}
std::vector<const Atom *> nonRingNbrs;
std::vector<const Atom *> ringNbrs;
std::set<unsigned int> ringNbrRanks;
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);
ringNbrRanks.insert(atomRanks[nbr->getIdx()]);
}
}
// std::cerr << "!!!! " << atom->getIdx() << " " << ringNbrRanks.size() <<
// " "
// << ringNbrs.size() << " " << nonRingNbrs.size() << std::endl;
switch (nonRingNbrs.size()) {
case 2:
// the ranks of the non ring neighbors must be different AND
// the ranks of the ring neighbors must be the same (see issue #8956)
res = atomRanks[nonRingNbrs[0]->getIdx()] !=
atomRanks[nonRingNbrs[1]->getIdx()];
res &= (ringNbrs.size() != ringNbrRanks.size());
break;
case 1:
if (ringNbrs.size() > ringNbrRanks.size()) {
res = true;
}
break;
case 0:
if (ringNbrs.size() == 4 && ringNbrRanks.size() == 3) {
res = true;
} else if (ringNbrs.size() == 3 && ringNbrRanks.size() == 2) {
res = true;
} else {
res = false;
}
break;
default:
res = false;
}
}
// std::cerr<<" candidate? "<<res<<std::endl;
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,
const std::vector<unsigned int> &atomRanks) {
PRECONDITION(possibleSpecialCases.size() >= mol.getNumAtoms(),
"bit vector too small");
possibleSpecialCases.reset();
if (!mol.getRingInfo()->isSymmSssr()) {
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, atomRanks)) {
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, atomRanks)) {
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)
// Also: cannot be SP2 hybridized or have a conjugated bond
// (this was Github #7434)
if (atom->getHybridization() == Atom::HybridizationType::SP3 &&
!MolOps::atomHasConjugatedBond(atom) &&
(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->getValence(Atom::ValenceType::EXPLICIT) == 4 ||
(atom->getValence(Atom::ValenceType::EXPLICIT) == 3 &&
atom->getFormalCharge() == 1)) {
// we also accept sulfur or selenium with either a positive charge
// or a double bond:
legalCenter = true;
}
}
}
}
if (legalCenter && !ranks.empty()) {
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 ||
((sinfo.controllingAtoms[0] == Atom::NOATOM &&
sinfo.controllingAtoms[1] == Atom::NOATOM) ||
(sinfo.controllingAtoms[2] == Atom::NOATOM &&
sinfo.controllingAtoms[3] == Atom::NOATOM))) {
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] != Atom::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] != Atom::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;
std::vector<Bond *> okbonds;
bool keep = true;
for (const auto atom : sg.getAtoms()) {
if (atom->getChiralTag() == Atom::ChiralType::CHI_UNSPECIFIED) {
keep = false;
} else {
okatoms.push_back(atom);
}
}
for (const auto bond : sg.getBonds()) {
if (bond->getStereo() != Bond::BondStereo::STEREOATROPCCW &&
bond->getStereo() != Bond::BondStereo::STEREOATROPCW) {
keep = false;
} else {
okbonds.push_back(bond);
}
}
if (keep) {
newsgs.push_back(sg);
} else if (!okatoms.empty()) {
newsgs.emplace_back(sg.getGroupType(), std::move(okatoms),
std::move(okbonds), 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) {
mol.clearProp("_needsDetectBondStereo");
// later we're going to need ring information, get it now if we don't
// have it already:
// NOTE, if called from the SMART code, the ring info will be DUMMY, and
// contains no information
if (!mol.getRingInfo()->isFindFastOrBetter()) {
MolOps::fastFindRings(mol);
}
// 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 = false; // flagPossibleStereoCenters;
bool hasPotentialStereoAtoms = false;
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;
} else if (!hasPotentialStereoAtoms) {
UINT_VECT ranks;
Chirality::INT_PAIR_VECT nbrs;
hasPotentialStereoAtoms =
isAtomPotentialChiralCenter(atom, mol, ranks, nbrs).first;
}
}
bool hasStereoBonds = false;
bool hasPotentialStereoBonds = false;
for (auto bond : mol.bonds()) {
if (cleanIt) {
bond->clearProp(common_properties::_CIPCode);
// 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) {
bool isSpecified = false;
for (auto nbond : mol.atomBonds(bond->getBeginAtom())) {
if (nbond->getBondDir() == Bond::ENDDOWNRIGHT ||
nbond->getBondDir() == Bond::ENDUPRIGHT) {
hasStereoBonds = true;
isSpecified = true;
break;
}
}
if (!hasStereoBonds) {
for (auto nbond : mol.atomBonds(bond->getEndAtom())) {
if (nbond->getBondDir() == Bond::ENDDOWNRIGHT ||
nbond->getBondDir() == Bond::ENDUPRIGHT) {
hasStereoBonds = true;
isSpecified = true;
break;
}
}
}
if (!hasPotentialStereoBonds && !isSpecified &&
shouldDetectDoubleBondStereo(bond)) {
hasPotentialStereoBonds = true;
}
}
if (!cleanIt && hasStereoBonds && hasPotentialStereoBonds) {
break; // no reason to keep iterating if we've already
// determined there are stereo bonds to consider
}
}
UINT_VECT atomRanks;
bool keepGoing = hasStereoAtoms | hasStereoBonds;
if (!keepGoing) {
keepGoing = flagPossibleStereoCenters &&
(hasPotentialStereoAtoms || hasPotentialStereoBonds);
}
bool changedStereoAtoms, changedStereoBonds;
while (keepGoing) {
if (hasStereoAtoms || hasPotentialStereoAtoms) {
// only do the CIP assignment if there's a chance of a stereo center
std::tie(hasStereoAtoms, changedStereoAtoms) =
Chirality::assignAtomChiralCodes(mol, atomRanks,
flagPossibleStereoCenters);
} else {
changedStereoAtoms = false;
}
if (hasStereoBonds || hasPotentialStereoBonds) {
// only do the CIP assignment if there's a chance of a stereo bond
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 (cleanIt) {
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, atomRanks);
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);
}
}
}
bool foundAtropisomer = 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) {
// see if there is an atropisomer bond connected to this bond
bool atomHasAtropisomer = false;
for (auto nbond : mol.atomBonds(bond->getBeginAtom())) {
if (nbond->getStereo() == Bond::STEREOATROPCCW ||
nbond->getStereo() == Bond::STEREOATROPCW) {
atomHasAtropisomer = true;
foundAtropisomer = true;
break;
}
}
if (!atomHasAtropisomer) {
bond->setBondDir(Bond::NONE);
}
}
// if we have either a double bond that involves a degree one atom and
// that is either crossed or STEREOANY, we need to clear the stereo and,
// possibly, direction. This can happen with imines that just have an
// implicit H on the N
if (bond->getBondType() == Bond::DOUBLE &&
(bond->getBondDir() == Bond::EITHERDOUBLE ||
bond->getStereo() == Bond::STEREOANY) &&
(bond->getBeginAtom()->getDegree() == 1 ||
bond->getEndAtom()->getDegree() == 1)) {
if (bond->getBondDir() == Bond::EITHERDOUBLE) {
bond->setBondDir(Bond::NONE);
}
bond->setStereo(Bond::STEREONONE);
}
// 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);
}
}
}
}
}
}
if (foundAtropisomer || Atropisomers::doesMolHaveAtropisomers(mol)) {
Atropisomers::cleanupAtropisomerStereoGroups(mol);
}
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) {
// in cases like imines without explicit Hs, we have double bonds with
// Unknown stereo but with only one neighbor on the N. Catch those and
// clear the stereochem
if (si.controllingAtoms.size() == 4 &&
si.controllingAtoms[0] != Atom::NOATOM &&
si.controllingAtoms[2] != Atom::NOATOM) {
bond->setStereoAtoms(si.controllingAtoms[0], si.controllingAtoms[2]);
bond->setStereo(Bond::BondStereo::STEREOANY);
} else {
bond->setStereo(Bond::BondStereo::STEREONONE);
}
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()) {
bond->clearProp(common_properties::_CIPCode);
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) {
Atropisomers::cleanupAtropisomerStereoGroups(mol);
Chirality::cleanupStereoGroups(mol);
}
}
bool canBeStereoBond(const Bond *bond) {
PRECONDITION(bond, "no bond");
if (bond->getBondType() != Bond::BondType::DOUBLE &&
bond->getBondType() != Bond::BondType::AROMATIC) {
return false;
}
auto beginAtom = bond->getBeginAtom();
auto endAtom = bond->getEndAtom();
for (const auto atom : {beginAtom, endAtom}) {
std::vector<int> nbrRanks;
for (auto nbrBond : bond->getOwningMol().atomBonds(atom)) {
if (nbrBond == bond) {
continue; // a bond is NOT its own neighbor
}
if (nbrBond->getBondType() == Bond::SINGLE) {
// if a neighbor has a wedge or hash bond, do NOT mark it as double
// crossed
if (nbrBond->getBondDir() == Bond::ENDUPRIGHT ||
nbrBond->getBondDir() == Bond::ENDDOWNRIGHT) {
return false;
}
// if a neighbor has a wiggle bond, do NOT mark it as crossed (although
// it is unknown
if (nbrBond->getBondDir() == Bond::BondDir::UNKNOWN &&
nbrBond->getBeginAtom() == atom) {
return false;
}
// if two neighbors havr the same CIP ranking, this is not stereo
const auto otherAtom = nbrBond->getOtherAtom(atom);
int rank;
if (RDKit::Chirality::getUseLegacyStereoPerception()) {
if (!otherAtom->getPropIfPresent(common_properties::_CIPRank, rank)) {
rank = -1;
}
} else { // NOT legacy stereo
if (!otherAtom->getPropIfPresent(common_properties::_ChiralAtomRank,
rank)) {
rank = -1;
}
}
if (rank >= 0) {
if (std::find(nbrRanks.begin(), nbrRanks.end(), rank) !=
nbrRanks.end()) {
return false;
} else {
nbrRanks.push_back(rank);
}
}
}
}
}
return true;
}
bool shouldBeACrossedBond(const Bond *bond) {
PRECONDITION(bond, "");
// double bond stereochemistry -
// if the bond isn't specified, then it should go in the mol block
// as "any", this was sf.net issue 2963522.
// two caveats to this:
// 1) if it's a ring bond, we'll only put the "any"
// in the mol block if the user specifically asked for it.
// Constantly seeing crossed bonds in rings, though maybe
// technically correct, is irritating.
// 2) if it's a terminal bond (where there's no chance of
// stereochemistry anyway), we also skip the any.
// this was sf.net issue 3009756
if (bond->getStereo() == Bond::STEREOANY) {
// see if any of the neighbors have a wiggle bond - if so, do NOT make this
// one a cross bond
for (auto nbrBond : bond->getOwningMol().atomBonds(bond->getBeginAtom())) {
if (nbrBond->getBondDir() == Bond::UNKNOWN &&
nbrBond->getBeginAtom()->getIdx() == bond->getBeginAtom()->getIdx()) {
return false;
}
}
for (auto nbrBond : bond->getOwningMol().atomBonds(bond->getEndAtom())) {
if (nbrBond->getBondDir() == Bond::UNKNOWN &&
nbrBond->getBeginAtom()->getIdx() == bond->getEndAtom()->getIdx()) {
return false;
}
}
return true; // crossed double bond
}
if (bond->getStereo() != Bond::BondStereo::STEREONONE) {
return false;
}
// if it is in a ring it is not makred as stereo.
// If either end is terminal, it is not stereo
if (!Chirality::detail::isBondPotentialStereoBond(bond)) {
return false;
}
// we don't know that it's explicitly unspecified (covered above with
// the ==STEREOANY check)
if (bond->getBondDir() == Bond::EITHERDOUBLE) {
return true; // crossed double bond
}
const auto beginAtom = bond->getBeginAtom();
const auto endAtom = bond->getEndAtom();
if (beginAtom->getDegree() > 1 && endAtom->getDegree() > 1 &&
(beginAtom->getTotalValence() - beginAtom->getTotalDegree()) == 1 &&
(endAtom->getTotalValence() - endAtom->getTotalDegree()) == 1) {
// we only do this if each atom only has one unsaturation
// FIX: this is the fix for github #2649, but we will need to
// change it once we start handling allenes properly
if (canBeStereoBond(bond)) {
return true; // crossed double bond
}
}
return false; // NOT crossed double bond
}
// only valid for single or aromatic bonds
int BondGetDirCode(const Bond::BondDir dir) {
int res = 0;
switch (dir) {
case Bond::NONE:
res = 0;
break;
case Bond::BEGINWEDGE:
res = 1;
break;
case Bond::BEGINDASH:
res = 6;
break;
case Bond::UNKNOWN:
res = 4;
break;
case Bond::BondDir::EITHERDOUBLE:
res = 3;
break;
default:
break;
}
return res;
}
void GetMolFileBondStereoInfo(
const Bond *bond,
const std::map<int, std::unique_ptr<RDKit::Chirality::WedgeInfoBase>>
&wedgeBonds,
const Conformer *conf, Bond::BondDir &dir, bool &reverse) {
PRECONDITION(bond, "");
reverse = false;
dir = Bond::NONE;
if (canHaveDirection(*bond)) {
// single bond stereo chemistry
dir = Chirality::detail::determineBondWedgeState(bond, wedgeBonds, conf);
// if this bond needs to be wedged it is possible that this
// wedging was determined by a chiral atom at the end of the
// bond (instead of at the beginning). In this case we need to
// reverse the begin and end atoms for the bond when we write
// the mol file
if ((dir == Bond::BEGINDASH) ||
(dir == Bond::BEGINWEDGE || dir == Bond::UNKNOWN)) {
auto wbi = wedgeBonds.find(bond->getIdx());
if (wbi != wedgeBonds.end() &&
wbi->second->getType() ==
Chirality::WedgeInfoType::WedgeInfoTypeChiral &&
static_cast<unsigned int>(wbi->second->getIdx()) !=
bond->getBeginAtomIdx()) {
reverse = true;
}
}
} else if (bond->getBondType() == Bond::DOUBLE) {
if (Chirality::shouldBeACrossedBond(bond)) {
dir = Bond::BondDir::EITHERDOUBLE;
}
}
}
void GetMolFileBondStereoInfo(
const Bond *bond,
const std::map<int, std::unique_ptr<RDKit::Chirality::WedgeInfoBase>>
&wedgeBonds,
const Conformer *conf, int &dirCode, bool &reverse) {
Bond::BondDir dir;
GetMolFileBondStereoInfo(bond, wedgeBonds, conf, dir, reverse);
dirCode = BondGetDirCode(dir);
}
void removeNonExplicit3DChirality(ROMol &mol) {
for (auto atom : mol.atoms()) {
if (atom->hasProp(common_properties::_NonExplicit3DChirality)) {
atom->clearProp(common_properties::_NonExplicit3DChirality);
atom->setChiralTag(Atom::CHI_UNSPECIFIED);
}
}
}
void addStereoAnnotations(ROMol &mol, std::string absLabel, std::string orLabel,
std::string andLabel, std::string cipLabel,
std::string bondLabel) {
auto sgs = mol.getStereoGroups();
assignStereoGroupIds(sgs);
boost::dynamic_bitset<> doneAts(mol.getNumAtoms());
for (const auto &sg : sgs) {
std::string gid = std::to_string(sg.getWriteId());
for (const auto atom : sg.getAtoms()) {
if (doneAts[atom->getIdx()]) {
BOOST_LOG(rdWarningLog) << "Warning: atom " << atom->getIdx()
<< " is in more than one stereogroup. Only the "
"label from the first group will be used."
<< std::endl;
continue;
}
std::string cip;
atom->getPropIfPresent(common_properties::_CIPCode, cip);
std::string lab;
switch (sg.getGroupType()) {
case StereoGroupType::STEREO_ABSOLUTE:
lab = absLabel;
doneAts.set(atom->getIdx());
break;
case StereoGroupType::STEREO_OR:
lab = orLabel;
doneAts.set(atom->getIdx());
break;
case StereoGroupType::STEREO_AND:
lab = andLabel;
doneAts.set(atom->getIdx());
break;
default:
break;
}
if (!lab.empty()) {
boost::algorithm::replace_all(lab, "{id}", gid);
if (!cip.empty()) {
boost::algorithm::replace_all(lab, "{cip}", cip);
}
atom->setProp(common_properties::atomNote, lab);
}
}
}
if (!cipLabel.empty()) {
for (auto atom : mol.atoms()) {
std::string cip;
if (!doneAts[atom->getIdx()] &&
atom->getPropIfPresent(common_properties::_CIPCode, cip)) {
std::string lab = cipLabel;
boost::algorithm::replace_all(lab, "{cip}", cip);
atom->setProp(common_properties::atomNote, lab);
}
}
}
if (!bondLabel.empty()) {
for (auto bond : mol.bonds()) {
std::string cip;
if (!bond->getPropIfPresent(common_properties::_CIPCode, cip)) {
if (bond->getStereo() == Bond::STEREOE) {
cip = "E";
} else if (bond->getStereo() == Bond::STEREOZ) {
cip = "Z";
}
}
if (!cip.empty()) {
std::string lab = bondLabel;
boost::algorithm::replace_all(lab, "{cip}", cip);
bond->setProp(common_properties::bondNote, lab);
}
}
}
}
} // namespace Chirality
namespace MolOps {
void assignStereochemistry(ROMol &mol, bool cleanIt, bool force,
bool flagPossibleStereoCenters) {
if (!force && mol.hasProp(common_properties::_StereochemDone)) {
return;
}
if (mol.needsUpdatePropertyCache()) {
mol.updatePropertyCache(false);
}
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 ((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;
bool needCleanupStereoGroups = false;
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);
needCleanupStereoGroups = true;
}
break;
case Atom::CHI_TETRAHEDRAL:
if (atom->getHybridization() != Atom::SP3) {
atom->setChiralTag(Atom::CHI_UNSPECIFIED);
needCleanupStereoGroups = true;
} 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;
}
}
if (needCleanupStereoGroups) {
Chirality::cleanupStereoGroups(mol);
}
}
#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++;
}
}
}
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();
boost::dynamic_bitset<> explicitAtoms;
explicitAtoms.resize(mol.getNumAtoms(), 0);
for (auto bond : mol.bonds()) {
auto bondDir = bond->getBondDir();
if (bondDir == Bond::BondDir::BEGINWEDGE ||
bondDir == Bond::BondDir::BEGINDASH) {
explicitAtoms[bond->getBeginAtom()->getIdx()] = 1;
}
}
for (auto atom : mol.atoms()) {
if (atom->getChiralTag() != Atom::ChiralType::CHI_UNSPECIFIED) {
explicitAtoms[atom->getIdx()] = 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;
}
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)) {
if (explicitAtoms[atom->getIdx()] == 0) {
atom->setProp(common_properties::_NonExplicit3DChirality, 1);
}
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[4];
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 (hasWigglyBond) {
continue;
}
auto v1 = *nbrs[0] - p0;
auto v2 = *nbrs[1] - p0;
auto v3 = *nbrs[2] - p0;
double chiralVol = v1.dotProduct(v2.crossProduct(v3));
bool chiralitySet = false;
if (chiralVol < -ZERO_VOLUME_TOL) {
atom->setChiralTag(Atom::CHI_TETRAHEDRAL_CW);
chiralitySet = true;
} else if (chiralVol > ZERO_VOLUME_TOL) {
atom->setChiralTag(Atom::CHI_TETRAHEDRAL_CCW);
chiralitySet = true;
} else if (nbrIdx == 4) {
// The first three neighbors are on the same plane as the chiral atom (or
// very close to it). If a 4th neighbor is present, let's see if this one
// determines a chiral volume
auto v4 = *nbrs[3] - p0;
// v4 would be in the opposite direction to v3
chiralVol = -v1.dotProduct(v2.crossProduct(v4));
if (chiralVol < -ZERO_VOLUME_TOL) {
atom->setChiralTag(Atom::CHI_TETRAHEDRAL_CW);
chiralitySet = true;
} else if (chiralVol > ZERO_VOLUME_TOL) {
atom->setChiralTag(Atom::CHI_TETRAHEDRAL_CCW);
chiralitySet = true;
} else {
atom->setChiralTag(Atom::CHI_UNSPECIFIED);
}
} else {
atom->setChiralTag(Atom::CHI_UNSPECIFIED);
}
if (chiralitySet && explicitAtoms[atom->getIdx()] == 0) {
atom->setProp<int>(common_properties::_NonExplicit3DChirality, 1);
}
}
}
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->needsUpdatePropertyCache()) {
atom->updatePropertyCache(false);
}
}
}
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.
if (!mol.getRingInfo()->isSymmSssr()) {
RDKit::MolOps::symmetrizeSSSR(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 {
needsDir[bond->getIdx()] = 1;
if (nbrDir == Bond::BondDir::NONE ||
nbrDir == Bond::BondDir::ENDDOWNRIGHT ||
nbrDir == Bond::BondDir::ENDUPRIGHT) {
needsDir[nbrBond->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()) {
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::ranges::sort(orderedBondsInPlay, [](const auto &a, const auto &b) {
// sort in decreasing order of priority
if (a.first != b.first) {
return a.first > b.first;
}
// in case of ties, use the bond index to decide the order
return a.second->getIdx() < b.second->getIdx();
});
// oof, now loop over the double bonds in that order and
// update their neighbor directionalities:
for (const auto& pairIter : orderedBondsInPlay) {
updateDoubleBondNeighbors(mol, pairIter.second, conf, needsDir,
singleBondCounts, singleBondNbrs);
}
}
void detectBondStereochemistry(ROMol &mol, int confId) {
if (!mol.getNumConformers()) {
return;
}
const Conformer &conf = mol.getConformer(confId);
setDoubleBondNeighborDirections(mol, &conf);
}
void clearSingleBondDirFlags(ROMol &mol, bool onlyWedgeFlags) {
for (auto bond : mol.bonds()) {
if (bond->getBondType() == Bond::SINGLE) {
if (bond->getBondDir() == Bond::UNKNOWN) {
bond->setProp(common_properties::_UnknownStereo, 1);
}
if (!onlyWedgeFlags ||
(bond->getBondDir() != Bond::BondDir::ENDDOWNRIGHT &&
bond->getBondDir() != Bond::BondDir::ENDUPRIGHT)) {
bond->setBondDir(Bond::NONE);
}
}
}
}
void clearDirFlags(ROMol &mol, bool onlyWedgeTypeBondDirs) {
for (auto bond : mol.bonds()) {
if (bond->getBondDir() == Bond::UNKNOWN ||
bond->getBondDir() == Bond::BondDir::EITHERDOUBLE) {
bond->setProp(common_properties::_UnknownStereo, 1);
}
if (onlyWedgeTypeBondDirs == false ||
(bond->getBondDir() != Bond::BondDir::ENDDOWNRIGHT &&
bond->getBondDir() != Bond::BondDir::ENDUPRIGHT)) {
bond->setBondDir(Bond::NONE);
}
}
}
void clearAllBondDirFlags(ROMol &mol) { clearDirFlags(mol, false); }
void setBondStereoFromDirections(ROMol &mol) {
mol.clearProp("_needsDetectBondStereo");
for (Bond *bond : mol.bonds()) {
if (bond->getBondType() == Bond::DOUBLE &&
bond->getStereo() != Bond::STEREOANY) {
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->needsUpdatePropertyCache()) {
atom->updatePropertyCache(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));
}
} // namespace MolOps
namespace Chirality {
void simplifyEnhancedStereo(ROMol &mol, bool removeAffectedStereoGroups) {
auto sgs = mol.getStereoGroups();
if (sgs.size() == 1) {
boost::dynamic_bitset<> chiralAts(mol.getNumAtoms());
for (const auto atom : mol.atoms()) {
if (atom->getChiralTag() > Atom::ChiralType::CHI_UNSPECIFIED &&
atom->getChiralTag() < Atom::ChiralType::CHI_OTHER) {
chiralAts.set(atom->getIdx(), 1);
}
}
for (const auto atm : sgs[0].getAtoms()) {
chiralAts.set(atm->getIdx(), 0);
}
if (chiralAts.none()) {
// all specified chiral centers are accounted for by this StereoGroup.
if (sgs[0].getGroupType() == StereoGroupType::STEREO_OR ||
sgs[0].getGroupType() == StereoGroupType::STEREO_AND) {
if (removeAffectedStereoGroups) {
std::vector<StereoGroup> empty;
mol.setStereoGroups(std::move(empty));
}
std::string label = sgs[0].getGroupType() == StereoGroupType::STEREO_OR
? "OR enantiomer"
: "AND enantiomer";
mol.setProp(common_properties::molNote, label);
// clear the chiral codes on the atoms in the group
for (const auto atm : sgs[0].getAtoms()) {
mol.getAtomWithIdx(atm->getIdx())
->clearProp(common_properties::_CIPCode);
}
}
}
}
}
std::vector<std::pair<unsigned int, unsigned int>> findMesoCenters(
const ROMol &mol, bool includeIsotopes, bool includeAtomMaps) {
std::vector<std::pair<unsigned int, unsigned int>> res;
boost::dynamic_bitset<> specifiedChiralAts(mol.getNumAtoms());
std::vector<unsigned int> ringStereoAts(mol.getNumAtoms(), mol.getNumAtoms());
for (const auto atom : mol.atoms()) {
atom->clearProp(common_properties::_mesoOtherAtom);
if (atom->getChiralTag() > Atom::ChiralType::CHI_UNSPECIFIED) {
specifiedChiralAts.set(atom->getIdx(), 1);
}
int otherIdx = -1;
if (atom->getPropIfPresent(common_properties::_ringStereoOtherAtom,
otherIdx) &&
otherIdx >= 0) {
ringStereoAts[atom->getIdx()] = static_cast<unsigned int>(otherIdx);
}
}
// easy case: no atoms with specified chirality
if (specifiedChiralAts.none()) {
return res;
}
// we will compare the atom ranks with chirality and with only chiral presence
// (so that we can distinguish centers with chirality specified and those
// without)
const bool breakTies = false;
const bool includeChiralPresence = true;
const bool includeStereoGroups = false;
const bool useNonStereoRanks = false;
bool includeChirality = true;
std::vector<unsigned int> chiralRanks;
Canon::rankMolAtoms(mol, chiralRanks, breakTies, includeChirality,
includeIsotopes, includeAtomMaps, includeChiralPresence,
includeStereoGroups, useNonStereoRanks);
includeChirality = false;
std::vector<unsigned int> presenceRanks;
Canon::rankMolAtoms(mol, presenceRanks, breakTies, includeChirality,
includeIsotopes, includeAtomMaps, includeChiralPresence,
includeStereoGroups, useNonStereoRanks);
for (auto i = 0u; i < mol.getNumAtoms(); ++i) {
if (!specifiedChiralAts[i]) {
continue;
}
for (auto j = i + 1; j < mol.getNumAtoms(); ++j) {
if (!specifiedChiralAts[j]) {
continue;
}
if (chiralRanks[i] != chiralRanks[j] &&
presenceRanks[i] == presenceRanks[j]) {
res.emplace_back(i, j);
} else if (ringStereoAts[i] == j && ringStereoAts[j] == i) {
// if both atoms are involved in ring stereo, they can have different
// ranks but still be meso centers. The canonical example of this is
// N[C@H]1CC[C@@H](O)CC1
std::unordered_set<unsigned int> iPresenceRanks;
std::unordered_set<unsigned int> iChiralRanks;
const auto atomi = mol.getAtomWithIdx(i);
for (const auto nbr : mol.atomNeighbors(atomi)) {
iPresenceRanks.insert(presenceRanks[nbr->getIdx()]);
iChiralRanks.insert(chiralRanks[nbr->getIdx()]);
}
if (iPresenceRanks.size() < atomi->getDegree()) {
res.emplace_back(i, j);
}
}
}
}
for (const auto &[i, j] : res) {
mol.getAtomWithIdx(i)->setProp<unsigned int>(
common_properties::_mesoOtherAtom, j);
mol.getAtomWithIdx(j)->setProp<unsigned int>(
common_properties::_mesoOtherAtom, i);
}
return res;
}
} // namespace Chirality
} // namespace RDKit
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