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No coords atropisomers - fix smiles output of atrop wedges after reordering (#7418)

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* removed string_view in favor of string for catch test

* add parsing and generation of atropisomers when coords not present

* changed string_view to string in catch test

* more docs

* reformulation of the docs

* make an error message a little bit more useful

* small optimization
clang-format

* add `BondWedgingParameters` to new function

* changes for CIP test errors

* Updated internal doc to match what it does

* changes per PR review

* removed cout statements in tests

---------

Co-authored-by: Greg Landrum <greg.landrum@gmail.com>
This commit is contained in:
tadhurst-cdd
2024-05-07 10:06:33 -05:00
committed by GitHub
parent f48c87444d
commit a2b149a806
20 changed files with 700 additions and 101 deletions
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361
Code/GraphMol/Atropisomers.cpp
View File

@@ -108,6 +108,46 @@ bool getBondFrameOfReference(const Bond *bond, const Conformer *conf,
return true;
}
Bond::BondDir getBondDirForAtropisomerNoConf(Bond::BondStereo bondStereo,
unsigned int whichEnd,
unsigned int whichBond) {
// the convention is that in the absence of coords, the coordiates are choosen
// with the lowest numbered atom of the atrop bond down, and the other atom
// straight up.
// On each end, the lowest numbered connecting atom is on the left
//
// a b
// \ /
// c
// |
// d
// / \ aaa
// e f
//
// where c > d
// a < b
// e < f
PRECONDITION(whichEnd <= 1, "whichEnd must be 0 or 1");
PRECONDITION(whichBond <= 1, "whichBond must be 0 or 1");
PRECONDITION(bondStereo == Bond::BondStereo::STEREOATROPCW ||
bondStereo == Bond::BondStereo::STEREOATROPCCW,
"bondStereo must be BondAtropisomerCW or BondAtropisomerCCW");
int flips = 0;
if (bondStereo == Bond::BondStereo::STEREOATROPCW) {
++flips;
}
if (whichBond == 1) {
++flips;
}
if (whichEnd == 1) {
++flips;
}
return flips % 2 ? Bond::BEGINDASH : Bond::BEGINWEDGE;
}
Bond::BondDir getBondDirForAtropisomer2d(RDGeom::Point3D bondVecs[2],
Bond::BondStereo bondStereo,
unsigned int whichEnd,
@@ -129,12 +169,13 @@ Bond::BondDir getBondDirForAtropisomer2d(RDGeom::Point3D bondVecs[2],
++flips;
}
if (bondVecs[1 - whichEnd].y < 0) {
++flips; // if the OTHER end if negative for the low index bond vec, it
++flips; // if the OTHER end is negative for the low index bond vec, it
// is a flip
}
return flips % 2 ? Bond::BEGINWEDGE : Bond::BEGINDASH;
}
Bond::BondDir getBondDirForAtropisomer3d(Bond *whichBond,
const Conformer *conf) {
// for 3D we mark it as wedge or hash depending on the z-value of the bond
@@ -204,6 +245,44 @@ bool getAtropIsomerEndVect(const AtropAtomAndBondVec &atomAndBondVec,
return true;
}
std::pair<bool, Bond::BondDir> getBondDir(
const Bond *bond, const AtropAtomAndBondVec &atomAndBondVec) {
// get the wedge dir for this end of the bond
// if the first bond 1 has a bondDir, use it
// if the second bond has a bond dir use the opposite of if
// if both bonds have a dir, make sure they are different
auto bond1Dir = atomAndBondVec.second[0]->getBondDir();
if (bond1Dir != Bond::BEGINWEDGE && bond1Dir != Bond::BEGINDASH) {
bond1Dir = Bond::NONE; // we dont care if it any thing else
}
auto bond2Dir = atomAndBondVec.second.size() == 2
? atomAndBondVec.second[1]->getBondDir()
: Bond::NONE;
if (bond2Dir != Bond::BEGINWEDGE && bond2Dir != Bond::BEGINDASH) {
bond2Dir = Bond::NONE;
}
// if both are set to a direction, they must NOT be the same - one
// must be a dash and the other a hash
if (bond1Dir != Bond::NONE && bond2Dir != Bond::NONE &&
bond1Dir == bond2Dir) {
BOOST_LOG(rdWarningLog)
<< "The bonds on one end of an atropisomer are both UP or both DOWN - atoms are: "
<< bond->getBeginAtomIdx() << " " << bond->getEndAtomIdx() << std::endl;
return {false, Bond::BondDir::NONE};
}
if (bond1Dir == Bond::BEGINWEDGE || bond2Dir == Bond::BEGINDASH) {
return {true, Bond::BondDir::BEGINWEDGE};
}
if (bond1Dir == Bond::BEGINDASH || bond2Dir == Bond::BEGINWEDGE) {
return {true, Bond::BondDir::BEGINDASH};
}
return {true, Bond::BondDir::NONE};
}
bool DetectAtropisomerChiralityOneBond(Bond *bond, ROMol &mol,
const Conformer *conf) {
// the approach is this:
@@ -217,11 +296,11 @@ bool DetectAtropisomerChiralityOneBond(Bond *bond, ROMol &mol,
// atrop bond. for each end of the main bond, we find a vector to reprent
// the neighbor atom with the smallest index as its projection onto the
// x=0 plane.
// (In 2d, this projection is on the y-AXIS for the end that does NOT have a
// wedge/hash bond, and on the z axis - out of the plane - for the end that
// does have a wedge/hash). The chirality is recorded as the direction we
// rotate from, atom 1's projection to atom2's proejection - either
// clockwise or counter clockwise
// (In 2d, this projection is on the y-AXIS for the end that does NOT have
// a wedge/hash bond, and on the z axis - out of the plane - for the end
// that does have a wedge/hash). The chirality is recorded as the
// direction we rotate from, atom 1's projection to atom2's proejection -
// either clockwise or counter clockwise
PRECONDITION(bond, "bad bond");
@@ -241,6 +320,52 @@ bool DetectAtropisomerChiralityOneBond(Bond *bond, ROMol &mol,
}
}
// the convention is that in the absence of coords, the coordiates are choosen
// with the lowest numbered atom of the atrop bond down, and the other atom
// straight up.
// On each end, the lowest numbered connecting atom is on the left
//
// a b
// \ /
// c
// |
// d
// / \ aaa
// e f
//
// where c > d
// a < b
// e < f
if (conf == nullptr) {
std::pair<bool, Bond::BondDir> bond1DirResult;
bond1DirResult = getBondDir(bond, atomAndBondVecs[0]);
if (!bond1DirResult.first) {
return false;
}
std::pair<bool, Bond::BondDir> bond2DirResult;
bond2DirResult = getBondDir(bond, atomAndBondVecs[1]);
if (!bond2DirResult.first) {
return false;
}
if (bond1DirResult.second == bond2DirResult.second) {
BOOST_LOG(rdWarningLog)
<< "inconsistent bond wedging for an atropisomer. Atoms are: "
<< bond->getBeginAtomIdx() << " " << bond->getEndAtomIdx()
<< std::endl;
return false;
}
if (bond1DirResult.second == Bond::BEGINWEDGE ||
bond2DirResult.second == Bond::BEGINDASH) {
bond->setStereo(Bond::BondStereo::STEREOATROPCCW);
} else if (bond1DirResult.second == Bond::BEGINDASH ||
bond2DirResult.second == Bond::BEGINWEDGE) {
bond->setStereo(Bond::BondStereo::STEREOATROPCW);
}
return true;
}
// create a frame of reference that has its X-axis along the atrop bond
RDGeom::Point3D xAxis, yAxis, zAxis;
@@ -265,27 +390,10 @@ bool DetectAtropisomerChiralityOneBond(Bond *bond, ROMol &mol,
// if the second bond has a bond dir use the opposite of if
// if both bonds have a dir, make sure they are different
auto bond1Dir = atomAndBondVecs[bondAtomIndex].second[0]->getBondDir();
if (bond1Dir != Bond::BEGINWEDGE && bond1Dir != Bond::BEGINDASH) {
bond1Dir = Bond::NONE; // we dont care if it any thing else
}
auto bond2Dir =
atomAndBondVecs[bondAtomIndex].second.size() == 2
? atomAndBondVecs[bondAtomIndex].second[1]->getBondDir()
: Bond::NONE;
if (bond2Dir != Bond::BEGINWEDGE && bond2Dir != Bond::BEGINDASH) {
bond2Dir = Bond::NONE;
}
std::pair<bool, Bond::BondDir> bondDirResult;
// if both are set to a direction, they must NOT be the same - one
// must be a dash and the other a hash
if (bond1Dir != Bond::NONE && bond2Dir != Bond::NONE &&
bond1Dir == bond2Dir) {
BOOST_LOG(rdWarningLog)
<< "The bonds on one end of an atropisomer are both UP or both DOWN - atoms are: "
<< bond->getBeginAtomIdx() << " " << bond->getEndAtomIdx()
<< std::endl;
bondDirResult = getBondDir(bond, atomAndBondVecs[bondAtomIndex]);
if (!bondDirResult.first) {
return false;
}
@@ -294,10 +402,10 @@ bool DetectAtropisomerChiralityOneBond(Bond *bond, ROMol &mol,
return false;
}
if (bond1Dir == Bond::BEGINWEDGE || bond2Dir == Bond::BEGINDASH) {
if (bondDirResult.second == Bond::BEGINWEDGE) {
bondVecs[bondAtomIndex].y *= 0.707;
bondVecs[bondAtomIndex].z = fabs(bondVecs[bondAtomIndex].y);
} else if (bond1Dir == Bond::BEGINDASH || bond2Dir == Bond::BEGINWEDGE) {
} else if (bondDirResult.second == Bond::BEGINDASH) {
bondVecs[bondAtomIndex].y *= 0.707;
bondVecs[bondAtomIndex].z = -fabs(bondVecs[bondAtomIndex].y);
}
@@ -410,8 +518,7 @@ void cleanupAtropisomerStereoGroups(ROMol &mol) {
}
void detectAtropisomerChirality(ROMol &mol, const Conformer *conf) {
PRECONDITION(conf, "no conformer");
PRECONDITION(&(conf->getOwningMol()) == &mol,
PRECONDITION(conf == nullptr || &(conf->getOwningMol()) == &mol,
"conformer does not belong to molecule");
std::set<Bond *> bondsToTry;
@@ -492,6 +599,169 @@ void getAllAtomIdsForStereoGroup(
}
}
bool WedgeBondFromAtropisomerOneBondNoConf(
Bond *bond, const ROMol &mol,
std::map<int, std::unique_ptr<RDKit::Chirality::WedgeInfoBase>>
&wedgeBonds) {
PRECONDITION(bond, "no bond");
AtropAtomAndBondVec atomAndBondVecs[2];
if (!getAtropisomerAtomsAndBonds(bond, atomAndBondVecs, mol)) {
return false; // not an atropisomer
}
// make sure we do not have wiggle bonds
for (auto atomAndBondVec : atomAndBondVecs) {
for (auto endBond : atomAndBondVec.second) {
if (endBond->getBondDir() == Bond::UNKNOWN) {
return false; // not an atropisomer)
}
}
}
// first see if any candidate bond is already set to a wedge or hash
// if so, we will use that bond as a wedge or hash
std::vector<int> useBondsAtEnd[2];
bool foundBondDir = false;
for (unsigned int whichEnd = 0; whichEnd < 2; ++whichEnd) {
for (unsigned int whichBond = 0;
whichBond < atomAndBondVecs[whichEnd].second.size(); ++whichBond) {
auto bondDir = atomAndBondVecs[whichEnd].second[whichBond]->getBondDir();
// see if it is a wedge or hash and its origin is the atom in the
// main bond
if ((bondDir == Bond::BEGINWEDGE || bondDir == Bond::BEGINDASH) &&
atomAndBondVecs[whichEnd].second[whichBond]->getBeginAtom() ==
atomAndBondVecs[whichEnd].first &&
canHaveDirection(*bond)) {
useBondsAtEnd[whichEnd].push_back(whichBond);
foundBondDir = true;
}
}
}
if (foundBondDir) {
for (unsigned int whichEnd = 0; whichEnd < 2; ++whichEnd) {
for (unsigned int whichBondIndex = 0;
whichBondIndex < useBondsAtEnd[whichEnd].size(); ++whichBondIndex) {
atomAndBondVecs[whichEnd]
.second[useBondsAtEnd[whichEnd][whichBondIndex]]
->setBondDir(getBondDirForAtropisomerNoConf(
bond->getStereo(), whichEnd,
useBondsAtEnd[whichEnd][whichBondIndex]));
}
}
return true;
}
// did not find a good bond dir - pick one to use
// we would like to have one that is not in a ring, and will be a wedge
const RingInfo *ri = bond->getOwningMol().getRingInfo();
int bestBondEnd = -1, bestBondNumber = -1;
bool bestBondIsSingle = false;
unsigned int bestRingCount = INT_MAX;
Bond::BondDir bestBondDir = Bond::BondDir::NONE;
for (unsigned int whichEnd = 0; whichEnd < 2; ++whichEnd) {
for (unsigned int whichBond = 0;
whichBond < atomAndBondVecs[whichEnd].second.size(); ++whichBond) {
auto bondToTry = atomAndBondVecs[whichEnd].second[whichBond];
if (!canHaveDirection(*bondToTry) ||
wedgeBonds.find(bondToTry->getIdx()) != wedgeBonds.end()) {
continue; // must be a single OR aromatic bond and not already
// spoken for by a chiral center
}
if (bondToTry->getBondDir() != Bond::BondDir::NONE) {
if (bondToTry->getBeginAtom()->getIdx() ==
atomAndBondVecs[whichEnd].first->getIdx()) {
BOOST_LOG(rdWarningLog)
<< "Wedge or hash bond found on atropisomer where not expected - atoms are: "
<< bond->getBeginAtomIdx() << " " << bond->getEndAtomIdx()
<< std::endl;
return false;
} else {
continue; // wedge or hash bond affecting the OTHER atom
// = perhaps a chiral center
}
}
auto ringCount = ri->numBondRings(bondToTry->getIdx());
if (ringCount > bestRingCount) {
continue;
}
else if (ringCount < bestRingCount) {
bestBondEnd = whichEnd;
bestBondNumber = whichBond;
bestRingCount = ringCount;
bestBondIsSingle = (bondToTry->getBondType() == Bond::BondType::SINGLE);
bestBondDir = getBondDirForAtropisomerNoConf(bond->getStereo(),
whichEnd, whichBond);
} else if (bestBondIsSingle &&
bondToTry->getBondType() != Bond::BondType::SINGLE) {
continue;
} else if (!bestBondIsSingle &&
bondToTry->getBondType() == Bond::BondType::SINGLE) {
bestBondEnd = whichEnd;
bestBondNumber = whichBond;
bestRingCount = ringCount;
bestBondIsSingle = true;
bestBondDir = getBondDirForAtropisomerNoConf(bond->getStereo(),
whichEnd, whichBond);
} else {
auto bondDir = getBondDirForAtropisomerNoConf(bond->getStereo(),
whichEnd, whichBond);
if (bestBondDir == Bond::BondDir::NONE ||
(bestBondDir == Bond::BondDir::BEGINDASH &&
bondDir == Bond::BondDir::BEGINWEDGE)) {
bestBondEnd = whichEnd;
bestBondNumber = whichBond;
bestRingCount = ringCount;
bestBondIsSingle =
(bondToTry->getBondType() == Bond::BondType::SINGLE);
bestBondDir = bondDir;
}
}
}
}
if (bestBondEnd >= 0) // we found a good one
{
// make sure the atoms on the bond are in the right order for the
// wedge/hash the atom on the end of the main bond must be listed
// first for the wedge/has bond
auto bestBond = atomAndBondVecs[bestBondEnd].second[bestBondNumber];
if (bestBond->getBeginAtom() != atomAndBondVecs[bestBondEnd].first) {
bestBond->setEndAtom(bestBond->getBeginAtom());
bestBond->setBeginAtom(atomAndBondVecs[bestBondEnd].first);
}
bestBond->setBondDir(bestBondDir);
auto newWedgeInfo = std::unique_ptr<RDKit::Chirality::WedgeInfoBase>(
new RDKit::Chirality::WedgeInfoAtropisomer(bond->getIdx(),
bestBondDir));
wedgeBonds[bestBond->getIdx()] = std::move(newWedgeInfo);
} else {
BOOST_LOG(rdWarningLog)
<< "Failed to find a good bond to set as UP or DOWN for an atropisomer - atoms are: "
<< bond->getBeginAtomIdx() << " " << bond->getEndAtomIdx() << std::endl;
return false;
}
return true;
}
bool WedgeBondFromAtropisomerOneBond2d(
Bond *bond, const ROMol &mol, const Conformer *conf,
std::map<int, std::unique_ptr<RDKit::Chirality::WedgeInfoBase>>
@@ -605,8 +875,8 @@ bool WedgeBondFromAtropisomerOneBond2d(
if (!canHaveDirection(*bondToTry) ||
wedgeBonds.find(bondToTry->getIdx()) != wedgeBonds.end()) {
continue; // must be a single OR aromatic bond and not already spoken
// for by a chiral center
continue; // must be a single OR aromatic bond and not already
// spoken for by a chiral center
}
if (bondToTry->getBondDir() != Bond::BondDir::NONE) {
@@ -680,11 +950,13 @@ bool WedgeBondFromAtropisomerOneBond2d(
bestBond->setEndAtom(bestBond->getBeginAtom());
bestBond->setBeginAtom(atomAndBondVecs[bestBondEnd].first);
}
// bonds[bestBondEnd][bestBondNumber]->setBondDir(bestBondDir);
bestBond->setBondDir(bestBondDir);
auto newWedgeInfo = std::unique_ptr<RDKit::Chirality::WedgeInfoBase>(
new RDKit::Chirality::WedgeInfoAtropisomer(bond->getIdx(),
bestBondDir));
wedgeBonds[bestBond->getIdx()] = std::move(newWedgeInfo);
} else {
BOOST_LOG(rdWarningLog)
<< "Failed to find a good bond to set as UP or DOWN for an atropisomer - atoms are: "
@@ -738,8 +1010,9 @@ bool WedgeBondFromAtropisomerOneBond3d(
}
}
// the following may seem redundant, since we just found the useBonds based
// on their bond dir PRESENCE, but this endures that the values are correct.
// the following may seem redundant, since we just found the useBonds
// based on their bond dir PRESENCE, but this endures that the values are
// correct.
if (useBonds.size() > 0) {
for (auto useBond : useBonds) {
@@ -843,10 +1116,11 @@ bool WedgeBondFromAtropisomerOneBond3d(
bestBond->setEndAtom(bestBond->getBeginAtom());
bestBond->setBeginAtom(atomAndBondVecs[bestBondEnd].first);
}
// bestBond->setBondDir(bestBondDir);
bestBond->setBondDir(bestBondDir);
auto newWedgeInfo = std::unique_ptr<RDKit::Chirality::WedgeInfoBase>(
new RDKit::Chirality::WedgeInfoAtropisomer(bond->getIdx(),
bestBondDir));
wedgeBonds[bestBond->getIdx()] = std::move(newWedgeInfo);
} else {
BOOST_LOG(rdWarningLog)
@@ -862,8 +1136,7 @@ void wedgeBondsFromAtropisomers(
const ROMol &mol, const Conformer *conf,
std::map<int, std::unique_ptr<RDKit::Chirality::WedgeInfoBase>>
&wedgeBonds) {
PRECONDITION(conf, "no conformer");
PRECONDITION(&(conf->getOwningMol()) == &mol,
PRECONDITION(conf == nullptr || &(conf->getOwningMol()) == &mol,
"conformer does not belong to molecule");
for (auto bond : mol.bonds()) {
auto bondStereo = bond->getStereo();
@@ -878,10 +1151,14 @@ void wedgeBondsFromAtropisomers(
continue;
}
if (conf->is3D()) {
WedgeBondFromAtropisomerOneBond3d(bond, mol, conf, wedgeBonds);
} else {
WedgeBondFromAtropisomerOneBond2d(bond, mol, conf, wedgeBonds);
if (conf) {
if (conf->is3D()) {
WedgeBondFromAtropisomerOneBond3d(bond, mol, conf, wedgeBonds);
} else {
WedgeBondFromAtropisomerOneBond2d(bond, mol, conf, wedgeBonds);
}
} else { // no conformer
WedgeBondFromAtropisomerOneBondNoConf(bond, mol, wedgeBonds);
}
}
}

97
Code/GraphMol/CIPLabeler/catch_tests.cpp
View File

@@ -24,6 +24,7 @@
#include <GraphMol/FileParsers/FileParsers.h>
#include <GraphMol/MarvinParse/MarvinParser.h>
#include <GraphMol/test_fixtures.h>
#include <GraphMol/Substruct/SubstructMatch.h>
#include "CIPLabeler.h"
#include "Digraph.h"
@@ -840,3 +841,99 @@ TEST_CASE("upsertTest", "[basic]") {
CHECK(smilesOut != "");
}
}
TEST_CASE("atropisomers", "[basic]") {
SECTION("atropisomers1") {
UseLegacyStereoPerceptionFixture useLegacy(false);
std::string rdbase = getenv("RDBASE");
std::vector<std::string> files = {
"BMS-986142_atrop5.sdf", "BMS-986142_atrop1.sdf",
"BMS-986142_atrop2.sdf", "JDQ443_atrop1.sdf",
"JDQ443_atrop2.sdf", "Mrtx1719_atrop1.sdf",
"Mrtx1719_atrop2.sdf", "RP-6306_atrop1.sdf",
"RP-6306_atrop2.sdf", "Sotorasib_atrop1.sdf",
"Sotorasib_atrop2.sdf", "ZM374979_atrop1.sdf",
"ZM374979_atrop2.sdf"};
for (auto file : files) {
auto fName =
rdbase + "/Code/GraphMol/FileParsers/test_data/atropisomers/" + file;
auto molsdf = MolFileToMol(fName, true, true, true);
REQUIRE(molsdf);
CIPLabeler::assignCIPLabels(*molsdf, 100000);
std::map<std::pair<unsigned int, unsigned int>, std::string> CIPVals;
for (auto bond : molsdf->bonds()) {
auto a1 = bond->getBeginAtomIdx();
auto a2 = bond->getEndAtomIdx();
if (a1 > a2) {
std::swap(a1, a2);
}
if (bond->hasProp(common_properties::_CIPCode)) {
CIPVals[std::make_pair(a1, a2)] =
bond->getProp<std::string>(common_properties::_CIPCode);
} else {
CIPVals[std::make_pair(a1, a2)] = "N/A";
}
}
molsdf->clearConformers();
SmilesWriteParams wp;
wp.canonical = false;
wp.doKekule = false;
unsigned int flags =
RDKit::SmilesWrite::CXSmilesFields::CX_MOLFILE_VALUES |
RDKit::SmilesWrite::CXSmilesFields::CX_ATOM_PROPS |
RDKit::SmilesWrite::CXSmilesFields::CX_BOND_CFG |
RDKit::SmilesWrite::CXSmilesFields::CX_BOND_ATROPISOMER;
SmilesParserParams pp;
pp.allowCXSMILES = true;
pp.sanitize = true;
auto smi = MolToCXSmiles(*molsdf, wp, flags);
auto newMol = SmilesToMol(smi, pp);
CIPLabeler::assignCIPLabels(*newMol, 100000);
std::map<std::pair<unsigned int, unsigned int>, std::string> newCIPVals;
for (auto bond : newMol->bonds()) {
auto a1 = bond->getBeginAtomIdx();
auto a2 = bond->getEndAtomIdx();
if (a1 > a2) {
std::swap(a1, a2);
}
if (bond->hasProp(common_properties::_CIPCode)) {
newCIPVals[std::make_pair(a1, a2)] =
bond->getProp<std::string>(common_properties::_CIPCode);
} else {
newCIPVals[std::make_pair(a1, a2)] = "N/A";
}
}
RDKit::SubstructMatchParameters params;
auto match = RDKit::SubstructMatch(*molsdf, *newMol, params);
for (auto thisBond : newMol->bonds()) {
unsigned int a1 = thisBond->getBeginAtomIdx();
unsigned int a2 = thisBond->getEndAtomIdx();
if (a1 > a2) {
std::swap(a1, a2);
}
unsigned int a1match = match[0][a1].second;
unsigned int a2match = match[0][a2].second;
if (a1match > a2match) {
std::swap(a1match, a2match);
}
CHECK(CIPVals[std::make_pair(a1match, a2match)] ==
newCIPVals[std::make_pair(a1, a2)]);
}
}
}
}

8
Code/GraphMol/Chirality.h
View File

@@ -301,8 +301,12 @@ RDKIT_GRAPHMOL_EXPORT void setStereoForBond(ROMol &mol, Bond *bond,
/// returns a map from bond idx -> controlling atom idx
RDKIT_GRAPHMOL_EXPORT
std::map<int, std::unique_ptr<Chirality::WedgeInfoBase>> pickBondsToWedge(
const ROMol &mol, const BondWedgingParameters *params = nullptr,
const Conformer *conf = nullptr);
const ROMol &mol, const BondWedgingParameters *params = nullptr);
RDKIT_GRAPHMOL_EXPORT
std::map<int, std::unique_ptr<Chirality::WedgeInfoBase>> pickBondsToWedge(
const ROMol &mol, const BondWedgingParameters *params,
const Conformer *conf);
RDKIT_GRAPHMOL_EXPORT void wedgeMolBonds(
ROMol &mol, const Conformer *conf = nullptr,

2
Code/GraphMol/FileParsers/CDXMLParser.cpp
View File

@@ -613,6 +613,8 @@ std::vector<std::unique_ptr<RWMol>> MolsFromCDXMLDataStream(
Atropisomers::detectAtropisomerChirality(
*res, &res->getConformer(confidx));
} else { // no Conformer
Atropisomers::detectAtropisomerChirality(*res, nullptr);
}
// now that atom stereochem has been perceived, the wedging

2
Code/GraphMol/FileParsers/MolFileStereochem.cpp
View File

@@ -228,8 +228,8 @@ void invertMolBlockWedgingInfo(ROMol &mol) {
}
void markUnspecifiedStereoAsUnknown(ROMol &mol, int confId) {
auto wedgeBonds = RDKit::Chirality::pickBondsToWedge(mol);
const auto conf = mol.getConformer(confId);
auto wedgeBonds = RDKit::Chirality::pickBondsToWedge(mol, nullptr, &conf);
for (auto b : mol.bonds()) {
if (b->getBondType() == Bond::DOUBLE) {
int dirCode;

30
Code/GraphMol/FileParsers/file_parsers_catch.cpp
View File

@@ -11,7 +11,7 @@
#include <fstream>
#include <string>
#include <sstream>
#include <string_view>
// #include <string_view>
#include <streambuf>
#include "RDGeneral/test.h"
@@ -1618,7 +1618,6 @@ H 0.635000 0.635000 0.635000
mol->addConformer(conf);
const std::string xyzblock = MolToXYZBlock(*mol, 0, 15);
std::cout << xyzblock << std::endl;
std::string xyzblock_expected = R"XYZ(7
CHEMBL506259
O 0.402012650000000 -0.132994360000000 1.000000170000000
@@ -5074,7 +5073,8 @@ M END
Chirality::reapplyMolBlockWedging(*m);
CHECK(m->getBondWithIdx(2)->getBondDir() == Bond::BondDir::NONE);
}
SECTION("Reapply the original wedging, regardless the bond type of wedged bonds") {
SECTION(
"Reapply the original wedging, regardless the bond type of wedged bonds") {
auto m = R"CTAB(
Mrv2311 04232413302D
@@ -6041,10 +6041,10 @@ TEST_CASE("MaeWriter basic testing", "[mae][MaeWriter][writer]") {
auto bondBlockStart = mae.find("m_bond[6]");
REQUIRE(bondBlockStart != std::string::npos);
std::string_view ctBlock(&mae[ctBlockStart], atomBlockStart - ctBlockStart);
std::string_view atomBlock(&mae[atomBlockStart],
bondBlockStart - atomBlockStart);
std::string_view bondBlock(&mae[bondBlockStart]);
std::string ctBlock(&mae[ctBlockStart], atomBlockStart - ctBlockStart);
std::string atomBlock(&mae[atomBlockStart],
bondBlockStart - atomBlockStart);
std::string bondBlock(&mae[bondBlockStart]);
// Check mol properties
CHECK(ctBlock.find("s_m_title") != std::string::npos);
@@ -6173,10 +6173,10 @@ TEST_CASE("MaeWriter basic testing", "[mae][MaeWriter][writer]") {
auto bondBlockStart = mae.find("m_bond[6]");
REQUIRE(bondBlockStart != std::string::npos);
std::string_view ctBlock(&mae[ctBlockStart], atomBlockStart - ctBlockStart);
std::string_view atomBlock(&mae[atomBlockStart],
bondBlockStart - atomBlockStart);
std::string_view bondBlock(&mae[bondBlockStart]);
std::string ctBlock(&mae[ctBlockStart], atomBlockStart - ctBlockStart);
std::string atomBlock(&mae[atomBlockStart],
bondBlockStart - atomBlockStart);
std::string bondBlock(&mae[bondBlockStart]);
// Check mol properties
CHECK(ctBlock.find("s_m_title") != std::string::npos);
@@ -6258,7 +6258,7 @@ TEST_CASE("MaeWriter basic testing", "[mae][MaeWriter][writer]") {
// Maeparser does not parse bond properties, so don't check them.
}
SECTION("Check reverse roundtrip") {
constexpr std::string_view maeBlock = R"MAE(f_m_ct {
std::string maeBlock = R"MAE(f_m_ct {
s_m_title
:::
""
@@ -6348,7 +6348,7 @@ TEST_CASE("MaeWriter basic testing", "[mae][MaeWriter][writer]") {
auto ctBlockStart = mae.find("f_m_ct");
REQUIRE(ctBlockStart != std::string::npos);
std::string_view ctBlock(&mae[ctBlockStart]);
std::string ctBlock(&mae[ctBlockStart]);
CHECK(ctBlock == MaeWriter::getText(*mol));
}
@@ -6616,8 +6616,8 @@ TEST_CASE(
auto bondBlockStart = mae.find("m_bond[2]");
REQUIRE(bondBlockStart != std::string::npos);
const std::string_view atomBlock(&mae[atomBlockStart],
bondBlockStart - atomBlockStart);
const std::string atomBlock(&mae[atomBlockStart],
bondBlockStart - atomBlockStart);
CHECK(atomBlock.find(" -2 ") != std::string::npos);
}

9
Code/GraphMol/MarvinParse/MarvinParser.cpp
View File

@@ -611,9 +611,12 @@ class MarvinCMLReader {
MolOps::assignChiralTypesFrom3D(*mol, conf3d->getId(), true);
}
if (conf || conf3d) {
Atropisomers::detectAtropisomerChirality(
*mol, conf != nullptr ? conf : conf3d);
if (conf) {
Atropisomers::detectAtropisomerChirality(*mol, conf);
} else if (conf3d) {
Atropisomers::detectAtropisomerChirality(*mol, conf3d);
} else {
Atropisomers::detectAtropisomerChirality(*mol, nullptr);
}
ClearSingleBondDirFlags(*mol);

107
Code/GraphMol/SmilesParse/CXSmilesOps.cpp
View File

@@ -1097,7 +1097,9 @@ bool parse_wedged_bonds(Iterator &first, Iterator last, RDKit::RWMol &mol,
if (atom->getIdx() != bond->getEndAtomIdx()) {
BOOST_LOG(rdWarningLog)
<< "atom " << atomIdx << " is not associated with bond "
<< bondIdx << " in w block" << std::endl;
<< bondIdx << "(" << bond->getBeginAtomIdx() + startAtomIdx << "-"
<< bond->getEndAtomIdx() + startAtomIdx << ")"
<< " in w block" << std::endl;
return false;
}
auto eidx = bond->getBeginAtomIdx();
@@ -2038,23 +2040,96 @@ std::string get_bond_config_block(
bd = Bond::BondDir::NONE;
}
if (atropisomerOnly) {
// on of the bonds on the beging atom of this bond must be an atropisomer
if (atropisomerOnly && bd == Bond::BondDir::NONE) {
continue;
}
if (bd == Bond::BondDir::NONE) {
continue;
}
bool foundAtropisomer = false;
// see if this one is an atropisomer
const Atom *firstAtom = bond->getBeginAtom();
bool isAnAtropisomer = false;
const Atom *firstAtom = bond->getBeginAtom();
if (bd == Bond::BondDir::BEGINDASH || bd == Bond::BondDir::BEGINWEDGE) {
for (auto bondNbr : mol.atomBonds(firstAtom)) {
if (bondNbr->getIdx() == bond->getIdx()) {
continue; // a bond is not its own neighbor
}
if (bondNbr->getStereo() == Bond::BondStereo::STEREOATROPCW ||
bondNbr->getStereo() == Bond::BondStereo::STEREOATROPCCW) {
foundAtropisomer = true;
isAnAtropisomer = true;
// if it is for an atropisomer and there are no coords, check to see
// if the wedge needs to be flipped based on the smiles reordering
if (!coordsIncluded && isAnAtropisomer) {
Atropisomers::AtropAtomAndBondVec atomAndBondVecs[2];
if (!Atropisomers::getAtropisomerAtomsAndBonds(
bondNbr, atomAndBondVecs, mol)) {
throw ValueErrorException("Internal error - should not occur");
// should not happend
} else {
unsigned int swaps = 0;
unsigned int firstReorderedIdx =
std::find(atomOrder.begin(), atomOrder.end(),
bondNbr->getBeginAtom()->getIdx()) -
atomOrder.begin();
unsigned int secondReorderedIdx =
std::find(atomOrder.begin(), atomOrder.end(),
bondNbr->getEndAtom()->getIdx()) -
atomOrder.begin();
if (firstReorderedIdx > secondReorderedIdx) {
++swaps;
}
for (unsigned int bondAtomIndex = 0; bondAtomIndex < 2;
++bondAtomIndex) {
if (atomAndBondVecs[bondAtomIndex].first == firstAtom)
continue; // swapped atoms on the side where the wedge bond
// is does NOT change the wedge bond
if (atomAndBondVecs[bondAtomIndex].second.size() == 2) {
unsigned int firstOtherAtomIdx =
atomAndBondVecs[bondAtomIndex]
.second[0]
->getOtherAtom(atomAndBondVecs[bondAtomIndex].first)
->getIdx();
unsigned int secondOtherAtomIdx =
atomAndBondVecs[bondAtomIndex]
.second[1]
->getOtherAtom(atomAndBondVecs[bondAtomIndex].first)
->getIdx();
unsigned int firstReorderedAtomIdx =
std::find(atomOrder.begin(), atomOrder.end(),
firstOtherAtomIdx) -
atomOrder.begin();
unsigned int secondReorderedAtomIdx =
std::find(atomOrder.begin(), atomOrder.end(),
secondOtherAtomIdx) -
atomOrder.begin();
if (firstReorderedAtomIdx > secondReorderedAtomIdx) {
++swaps;
}
}
}
if (swaps % 2) {
bd = (bd == Bond::BondDir::BEGINWEDGE)
? Bond::BondDir::BEGINDASH
: Bond::BondDir::BEGINWEDGE;
}
}
}
break;
}
}
if (!foundAtropisomer) {
}
if (atropisomerOnly) {
// one of the bonds on the beginning atom of this bond must be an
// atropisomer
if (!isAnAtropisomer) {
continue;
}
} else { // atropisomeronly is FALSE - check for a wedging caused by
@@ -2109,8 +2184,9 @@ std::string get_bond_config_block(
std::string wType = "";
if (bd == Bond::BondDir::UNKNOWN) {
wType = "w";
} else if (coordsIncluded) {
} else if (coordsIncluded || isAnAtropisomer) {
// we only do wedgeUp and wedgeDown if coordinates are being output
// or its an atropisomer
if (bd == Bond::BondDir::BEGINWEDGE) {
wType = "wU";
} else if (bd == Bond::BondDir::BEGINDASH) {
@@ -2354,12 +2430,13 @@ std::string getCXExtensions(const ROMol &mol, std::uint32_t flags) {
// do the CX_BOND_ATROPISOMER only if CX_BOND_CFG s not done. CX_BOND_CFG
// includes the atropisomer wedging
else if (flags & SmilesWrite::CXSmilesFields::CX_BOND_ATROPISOMER) {
if (conf) {
Atropisomers::wedgeBondsFromAtropisomers(mol, conf, wedgeBonds);
}
bool includeCoords = flags & SmilesWrite::CXSmilesFields::CX_COORDS &&
mol.getNumConformers();
if (includeCoords) {
Atropisomers::wedgeBondsFromAtropisomers(mol, conf, wedgeBonds);
} else {
Atropisomers::wedgeBondsFromAtropisomers(mol, nullptr, wedgeBonds);
}
const auto cfgblock = get_bond_config_block(
mol, atomOrder, bondOrder, includeCoords, wedgeBonds, true);
appendToCXExtension(cfgblock, res);

9
Code/GraphMol/SmilesParse/SmilesParse.cpp
View File

@@ -458,8 +458,13 @@ std::unique_ptr<RWMol> MolFromSmiles(const std::string &smiles,
res->updatePropertyCache(false);
MolOps::assignChiralTypesFrom3D(*res, conf3d->getId(), true);
}
if (conf || conf3d) {
Atropisomers::detectAtropisomerChirality(*res, conf ? conf : conf3d);
if (conf) {
Atropisomers::detectAtropisomerChirality(*res, conf);
} else if (conf3d) {
Atropisomers::detectAtropisomerChirality(*res, conf3d);
} else {
Atropisomers::detectAtropisomerChirality(*res, nullptr);
}
if (res && (params.sanitize || params.removeHs)) {

18
Code/GraphMol/SmilesParse/cxsmiles_test.cpp
View File

@@ -790,7 +790,8 @@ void testOneAtropisomers(const SmilesTest *smilesTest) {
MolToCXSmiles(*smilesMol, ps, flags, RestoreBondDirOptionClear);
generateNewExpectedFilesIfSoSpecified(fName + ".NEW3.cxsmi", smilesOut);
CHECK(getExpectedValue(expectedFileName) == smilesOut);
auto expected = getExpectedValue(expectedFileName);
CHECK(expected == smilesOut);
}
smilesMol =
@@ -826,7 +827,7 @@ void testOneAtropisomers(const SmilesTest *smilesTest) {
} catch (const RDKit::KekulizeException &e) {
outMolStr = "";
} catch (...) {
throw; // re-trhow the error if not a kekule error
throw; // re-throw the error if not a kekule error
}
if (outMolStr == "") {
RDKit::Chirality::reapplyMolBlockWedging(*smilesMol);
@@ -1023,6 +1024,7 @@ void testOne3dChiral(const SmilesTest *smilesTest) {
TEST_CASE("testAtropisomersInCXSmiles") {
{
std::list<SmilesTest> smiTests{
SmilesTest("ShortAtropisomerNoCoords.cxsmi", true, 14, 15),
SmilesTest("ShortAtropisomer.cxsmi", true, 14, 15),
SmilesTest("ShortAtropisomerArom.cxsmi", true, 14, 15),
SmilesTest("AtropManyChirals.cxsmi", true, 20, 20),
@@ -1344,15 +1346,11 @@ TEST_CASE("SMILES CANONICALIZATION") {
}
molCount++;
try {
if (molBlock.length() > 25) {
std::unique_ptr<RWMol> mol(MolBlockToMol(molBlock));
std::string smiles = MolToCXSmiles(*mol);
if (molBlock.length() > 25) {
std::unique_ptr<RWMol> mol(MolBlockToMol(molBlock));
std::string smiles = MolToCXSmiles(*mol);
testSmilesCanonicalization(smiles);
}
} catch (...) {
std::cout << "failed on mol " << molCount << std::endl;
testSmilesCanonicalization(smiles);
}
}
}

1
Code/GraphMol/SmilesParse/test_data/ShortAtropisomerNoCoords.cxsmi Normal file
View File

@@ -0,0 +1 @@
CC1=C(N2C=CC=C2C)C(C)CCC1 |wU:2.9|

1
Code/GraphMol/SmilesParse/test_data/ShortAtropisomerNoCoords.cxsmi.expected.cxsmi Normal file
View File

@@ -0,0 +1 @@
CC1=C(n2cccc2C)C(C)CCC1 |wU:2.9|

2
Code/GraphMol/SmilesParse/test_data/ShortAtropisomerNoCoords.cxsmi.expected.mrv Normal file
View File

@@ -0,0 +1,2 @@
<?xml version="1.0" encoding="utf-8"?>
<cml xmlns="http://www.chemaxon.com" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.chemaxon.com http://www.chemaxon.com/marvin/schema/mrvSchema_20_20_0.xsd"><MDocument><MChemicalStruct><molecule molID="m1"><atomArray><atom id="a1" elementType="C" x2="3" y2="0.00000"/><atom id="a2" elementType="C" x2="1.5" y2="0.00000"/><atom id="a3" elementType="C" x2="0.75" y2="-1.29904"/><atom id="a4" elementType="N" x2="1.5" y2="-2.59808"/><atom id="a5" elementType="C" x2="2.99178" y2="-2.75487"/><atom id="a6" elementType="C" x2="3.30365" y2="-4.22209"/><atom id="a7" elementType="C" x2="2.00461" y2="-4.97209"/><atom id="a8" elementType="C" x2="0.889895" y2="-3.96839"/><atom id="a9" elementType="C" x2="-0.577326" y2="-4.28026"/><atom id="a10" elementType="C" x2="-0.75" y2="-1.29904"/><atom id="a11" elementType="C" x2="-1.5" y2="-2.59808"/><atom id="a12" elementType="C" x2="-1.5" y2="0.00000"/><atom id="a13" elementType="C" x2="-0.75" y2="1.29904"/><atom id="a14" elementType="C" x2="0.75" y2="1.29904"/></atomArray><bondArray><bond id="b1" atomRefs2="a1 a2" order="1"/><bond id="b2" atomRefs2="a2 a3" order="2"/><bond id="b3" atomRefs2="a3 a4" order="1"/><bond id="b4" atomRefs2="a4 a5" order="1"/><bond id="b5" atomRefs2="a5 a6" order="2"/><bond id="b6" atomRefs2="a6 a7" order="1"/><bond id="b7" atomRefs2="a7 a8" order="2"/><bond id="b8" atomRefs2="a8 a9" order="1"/><bond id="b9" atomRefs2="a3 a10" order="1"><bondStereo>W</bondStereo></bond><bond id="b10" atomRefs2="a10 a11" order="1"/><bond id="b11" atomRefs2="a10 a12" order="1"/><bond id="b12" atomRefs2="a12 a13" order="1"/><bond id="b13" atomRefs2="a13 a14" order="1"/><bond id="b14" atomRefs2="a14 a2" order="1"/><bond id="b15" atomRefs2="a8 a4" order="1"/></bondArray></molecule></MChemicalStruct></MDocument></cml>

41
Code/GraphMol/SmilesParse/test_data/ShortAtropisomerNoCoords.cxsmi.expected.sdf Normal file
View File

@@ -0,0 +1,41 @@
RDKit 2D
0 0 0 0 0 0 0 0 0 0999 V3000
M V30 BEGIN CTAB
M V30 COUNTS 14 15 0 0 0
M V30 BEGIN ATOM
M V30 1 C 3.000000 0.000000 0.000000 0
M V30 2 C 1.500000 0.000000 0.000000 0
M V30 3 C 0.750000 -1.299038 0.000000 0
M V30 4 N 1.500000 -2.598076 0.000000 0
M V30 5 C 2.991783 -2.754869 0.000000 0
M V30 6 C 3.303650 -4.222090 0.000000 0
M V30 7 C 2.004612 -4.972090 0.000000 0
M V30 8 C 0.889895 -3.968394 0.000000 0
M V30 9 C -0.577326 -4.280262 0.000000 0
M V30 10 C -0.750000 -1.299038 0.000000 0
M V30 11 C -1.500000 -2.598076 0.000000 0
M V30 12 C -1.500000 0.000000 0.000000 0
M V30 13 C -0.750000 1.299038 0.000000 0
M V30 14 C 0.750000 1.299038 0.000000 0
M V30 END ATOM
M V30 BEGIN BOND
M V30 1 1 1 2
M V30 2 2 2 3
M V30 3 1 3 4
M V30 4 1 4 5
M V30 5 2 5 6
M V30 6 1 6 7
M V30 7 2 7 8
M V30 8 1 8 9
M V30 9 1 3 10 CFG=1
M V30 10 1 10 11
M V30 11 1 10 12
M V30 12 1 12 13
M V30 13 1 13 14
M V30 14 1 14 2
M V30 15 1 8 4
M V30 END BOND
M V30 END CTAB
M END

1
Code/GraphMol/SmilesParse/test_data/ShortAtropisomerNoCoords.cxsmi.expected2.cxsmi Normal file
View File

@@ -0,0 +1 @@
CC1=C(n2cccc2C)C(C)CCC1 |wU:2.9|

1
Code/GraphMol/SmilesParse/test_data/ShortAtropisomerNoCoords.cxsmi.expected3.cxsmi Normal file
View File

@@ -0,0 +1 @@
CC1=C(n2cccc2C)C(C)CCC1 |wU:2.9|

22
Code/GraphMol/WedgeBonds.cpp
View File

@@ -341,6 +341,16 @@ int pickBondToWedge(
// returns map of bondIdx -> bond begin atom for those bonds that
// need wedging.
std::map<int, std::unique_ptr<Chirality::WedgeInfoBase>> pickBondsToWedge(
const ROMol &mol, const BondWedgingParameters *params) {
const Conformer *conf = nullptr;
if (mol.getNumConformers()) {
conf = &mol.getConformer();
}
return pickBondsToWedge(mol, params, conf);
}
std::map<int, std::unique_ptr<Chirality::WedgeInfoBase>> pickBondsToWedge(
const ROMol &mol, const BondWedgingParameters *params,
const Conformer *conf) {
@@ -388,15 +398,7 @@ std::map<int, std::unique_ptr<Chirality::WedgeInfoBase>> pickBondsToWedge(
wedgeInfo[bnd1] = std::move(wi);
}
}
if (conf == nullptr) {
if (mol.getNumConformers()) {
conf = &mol.getConformer();
}
}
if (conf) {
RDKit::Atropisomers::wedgeBondsFromAtropisomers(mol, conf, wedgeInfo);
}
RDKit::Atropisomers::wedgeBondsFromAtropisomers(mol, conf, wedgeInfo);
return wedgeInfo;
}
@@ -472,7 +474,7 @@ void wedgeMolBonds(ROMol &mol, const Conformer *conf,
MolOps::findSSSR(mol);
}
auto wedgeBonds = Chirality::pickBondsToWedge(mol, params);
auto wedgeBonds = Chirality::pickBondsToWedge(mol, params, conf);
// loop over the bonds we need to wedge:
for (const auto &[wbi, wedgeInfo] : wedgeBonds) {

89
Docs/Book/RDKit_Book.rst
View File

@@ -2234,6 +2234,46 @@ Note: the RDKit software makes no attempt to determine if the bond is actually
rotationally constrained. If the bond meets the requirements above, it is
marked as an atropisomer.
Internal Representation of Atropisomers
=======================================
To help with the rest of the explanation, we include the bond indices in the molecule drawing:
.. testsetup::
'CC1=CC=CC(I)=C1N1C(C)=CC=C1Br |wU:7.7,(18.31,-9.57,;17.45,-9.08,;17.44,-8.08,;16.58,-7.58,;15.71,-8.08,;15.71,-9.08,;14.84,-9.58,;16.58,-9.58,;16.58,-10.58,;17.38,-11.17,;18.34,-10.87,;17.08,-12.12,;16.07,-12.12,;15.77,-11.17,;14.81,-10.87,)|'
.. image:: images/atrop_representation1.png
Here's part of the Debug output for that molecule::
Atoms:
...
1 6 C chg: 0 deg: 3 exp: 4 imp: 0 hyb: SP2 arom?: 1
...
5 6 C chg: 0 deg: 3 exp: 4 imp: 0 hyb: SP2 arom?: 1
...
7 6 C chg: 0 deg: 3 exp: 4 imp: 0 hyb: SP2 arom?: 1
8 7 N chg: 0 deg: 3 exp: 3 imp: 0 hyb: SP2 arom?: 1
9 6 C chg: 0 deg: 3 exp: 4 imp: 0 hyb: SP2 arom?: 1
...
13 6 C chg: 0 deg: 3 exp: 4 imp: 0 hyb: SP2 arom?: 1
...
Bonds:
...
6 5->7 order: a conj?: 1 aromatic?: 1
7 7->8 order: 1 stereo: CCW bonds: (14 6 8 15) conj?: 1
8 8->9 order: a conj?: 1 aromatic?: 1
...
14 7->1 order: a dir: wedge conj?: 1 aromatic?: 1
15 13->8 order: a conj?: 1 aromatic?: 1
This tells us that bond 7 is atropisomeric and that when looking down the bond
(from atom C7 to atom N8), the rotation direction between bonds 14 and 8 (these
are the bonds to the lowest numbered atoms on each of the atropisomeric bond) is
counterclockwise (CCW).
Formats supporting atropisomers
===============================
@@ -2280,6 +2320,54 @@ an atropisomer bond, the actual stereochemistry of the bond is determined by the
.. image:: images/atrop_example5.png
Interpreting atropisomers without coordinates
=============================================
Just as it is possible to interpret atomic and double bond stereochemistry from
SMILES without providing atomic coordinates, the RDKit adopts (starting with the
2024.03.2 release) a convention for interpreting bond wedge information in
CXSMILES that do not have coordinates provided.
In order to understand how this representation works, a quick digression is necessary to explain the difference in the way bonds are numbered in CXSMILES and the RDKit.
In the RDKit ring closure bonds are added last; they are the highest numbered bonds in the molecule. In CXSMILES, the ring closure bonds are added immediately upon closing the ring.
Here's an illustration of this for the SMILES ``CC1=CC=CC(I)=C1N1C(C)=CC=C1Br``; the RDKit bond numbering (what we saw above) is shown first and the CXSMILES numbering is shown second.
.. testsetup::
'CC1=CC=CC(I)=C1N1C(C)=CC=C1Br |wU:7.7|'
.. image:: images/atrop_representation2.png
To describe this atropisomer in CXSMILES without using coordinates, we adopt the convention that the atropisomeric bond's stereochemistry is ``CCW`` when the bond to the lowest-numbered neighbor of the start atom
(in this case the neighbor connected via bond 7) is wedged and write the CXSMILES for this molecule as ``CC1=CC=CC(I)=C1N1C(C)=CC=C1Br |wU:7.7||``. The stereo values for all possible combinations are shown here:
+-------+----+-------+-------+--------+------------+
| | | bond | | | |
| from | to | index | type | stereo | |
+=======+====+=======+=======+========+============+
| 7 | 1 | 7 | wedge | CCW | ``wU7.7`` |
+-------+----+-------+-------+--------+------------+
| 7 | 5 | 6 | wedge | CW | ``wU7.6`` |
+-------+----+-------+-------+--------+------------+
| 8 | 9 | 9 | wedge | CW | ``wU8.9`` |
+-------+----+-------+-------+--------+------------+
| 8 | 13 | 14 | wedge | CCW | ``wU8.14`` |
+-------+----+-------+-------+--------+------------+
| 7 | 1 | 7 | dash | CW | ``wD7.7`` |
+-------+----+-------+-------+--------+------------+
| 7 | 5 | 6 | dash | CCW | ``wD7.6`` |
+-------+----+-------+-------+--------+------------+
| 8 | 9 | 9 | dash | CCW | ``wD8.9`` |
+-------+----+-------+-------+--------+------------+
| 8 | 13 | 14 | dash | CW | ``wD8.14`` |
+-------+----+-------+-------+--------+------------+
It's also possible to wedge multiple neighbor bonds around an atropisomeric bond, but the wedging must be consistent based on the table above;
so the CXSMILES ``CC1=CC=CC(I)=C1N1C(C)=CC=C1Br |wD:7.7,wU:8.9|`` is valid, but ``CC1=CC=CC(I)=C1N1C(C)=CC=C1Br |wD:7.7,wU:8.14|`` is not.
Validation of Atropisomers
==========================
@@ -2294,7 +2382,6 @@ Atropisomers are supported in the canonicalization algorithm of RDKit. They are
substructure searching and similarity searching at this time.
Query Features in Molecule Drawings
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