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rdkit/Code/GraphMol/FileParsers/testAtropisomers.cpp
Yakov Pechersky c25abde7cf Include macrocycles in atropisomer calculation by not sanitizing them away (#7291) 
* Include macrocycles in atropisomer calculation

Previously, atropisomeric bonds were sanitized away if they were part of a "ring bond", which happens in macrocyclic systems.
None of the existing test cases fail if that sanitization check is removed.
The sanitization step is removed to support biaryls that are part of a larger macrocyclic system.
A set of test cases is included that cover potential macrocyclic atropisomeric systems

* Remove unmentioned files

* Keep ring check, and narrow it to when bond is in as many rings as atoms

* exclude atropisomer bonds if in rings < 8 atoms

Co-authored-by: tadhurst-cdd <112502803+tadhurst-cdd@users.noreply.github.com>

* Clarify macrocycle behavior in RDKit book

* fix typo

---------

Co-authored-by: tadhurst-cdd <112502803+tadhurst-cdd@users.noreply.github.com>
2024-04-09 06:05:25 +02:00

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//
// Copyright (C) 2002-2021 Collaboartive Drug Discovery 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 <RDGeneral/RDLog.h>
#include <GraphMol/RDKitBase.h>
#include <GraphMol/FileParsers/FileParsers.h>
#include <GraphMol/FileParsers/SequenceParsers.h>
#include <GraphMol/FileParsers/SequenceWriters.h>
#include <GraphMol/FileParsers/MolFileStereochem.h>
#include <GraphMol/Depictor/RDDepictor.h>
#include <GraphMol/ChemReactions/Reaction.h>
#include <GraphMol/ChemReactions/ReactionParser.h>
#include <GraphMol/SmilesParse/SmilesParse.h>
#include <GraphMol/SmilesParse/SmilesWrite.h>
#include <GraphMol/SmilesParse/SmilesWrite.h>
#include <GraphMol/Atropisomers.h>
#include <GraphMol/Chirality.h>
#include <string>
#include <fstream>
#include <boost/lexical_cast.hpp>
#include <filesystem>
using namespace RDKit;
class MolAtropTest {
public:
public:
std::string testToRun;
bool generateExpectedFiles;
MolAtropTest() {
testToRun = "";
generateExpectedFiles = false;
}
public:
class MolTest {
public:
unsigned int atomCount;
unsigned int bondCount;
std::string fileName;
bool expectedResult;
MolTest(std::string fileNameInit, bool expectedResultInit,
int atomCountInit, int bondCountInit)
: atomCount(atomCountInit),
bondCount(bondCountInit),
fileName(fileNameInit),
expectedResult(expectedResultInit){};
};
void generateNewExpectedFilesIfSoSpecified(std::string filename,
std::string dataToWrite) {
if (generateExpectedFiles) {
std::ofstream out;
out.open(filename);
out << dataToWrite;
}
}
std::string GetExpectedValue(std::string expectedFileName) {
std::stringstream expectedMolStr;
std::ifstream in;
in.open(expectedFileName);
expectedMolStr << in.rdbuf();
return expectedMolStr.str();
}
void testMolFiles(const MolTest *molFileTest) {
BOOST_LOG(rdInfoLog) << "testing mol files with atropisomers" << std::endl;
std::string rdbase = getenv("RDBASE");
std::string fName = rdbase +
"/Code/GraphMol/FileParsers/test_data/atropisomers/" +
molFileTest->fileName;
// first pass - no sanitiaton, but reapplyMolBlockWedging is ON
try {
std::unique_ptr<RWMol> mol(MolFileToMol(fName, false, false, false));
RDKit::Chirality::removeNonExplicit3DChirality(*mol);
TEST_ASSERT(mol != nullptr);
TEST_ASSERT(mol->getNumAtoms() == molFileTest->atomCount)
TEST_ASSERT(mol->getNumBonds() == molFileTest->bondCount)
{
MolOps::Kekulize(*mol);
RDKit::Chirality::reapplyMolBlockWedging(*mol);
std::string outMolStr = MolToMolBlock(*mol, true, 0, true, true);
generateNewExpectedFilesIfSoSpecified(fName + ".NEW.sdf", outMolStr);
TEST_ASSERT(GetExpectedValue(fName + ".expected.sdf") == outMolStr);
}
// 2nd pass without reapplying the mol block wedging -
// the itropisomers will be marked automatically
// SANITIZATION IS ON
mol = std::unique_ptr<RWMol>(MolFileToMol(fName, true, false, false));
RDKit::Chirality::removeNonExplicit3DChirality(*mol);
{
MolOps::Kekulize(*mol);
std::string outMolStr = MolToMolBlock(*mol, true, 0, true, true);
generateNewExpectedFilesIfSoSpecified(fName + ".NEW2.sdf", outMolStr);
TEST_ASSERT(GetExpectedValue(fName + ".expected2.sdf") == outMolStr);
}
// CXSMILES
mol = std::unique_ptr<RWMol>(MolFileToMol(fName, false, false, false));
RDKit::Chirality::removeNonExplicit3DChirality(*mol);
{
std::string expectedFileName = fName + ".expected.cxsmi";
SmilesWriteParams ps;
ps.canonical = false;
ps.doKekule = true;
unsigned int flags = SmilesWrite::CXSmilesFields::CX_COORDS |
SmilesWrite::CXSmilesFields::CX_MOLFILE_VALUES |
SmilesWrite::CXSmilesFields::CX_ATOM_PROPS |
SmilesWrite::CXSmilesFields::CX_BOND_CFG |
SmilesWrite::CXSmilesFields::CX_ENHANCEDSTEREO
//| SmilesWrite::CXSmilesFields::CX_ALL
;
std::string smilesOut =
MolToCXSmiles(*mol, ps, flags, RestoreBondDirOptionTrue);
generateNewExpectedFilesIfSoSpecified(fName + ".NEW.cxsmi", smilesOut);
TEST_ASSERT(GetExpectedValue(fName + ".expected.cxsmi") == smilesOut);
}
BOOST_LOG(rdInfoLog) << "done" << std::endl;
} catch (const std::exception &e) {
if (molFileTest->expectedResult != false) {
throw;
}
return;
}
TEST_ASSERT(molFileTest->expectedResult == true);
return;
}
void RunTests() {
// the molecule tests
if (testToRun == "" || testToRun == "sdfTests") {
std::list<MolTest> sdfTests{
MolTest("atropWedgeTest.sdf", true, 16, 16),
MolTest("AtropTest.sdf", true, 38, 41),
MolTest("AtropManyChiralsEnhanced.sdf", true, 20, 20),
MolTest("AtropManyChiralsEnhanced2.sdf", true, 20, 20),
MolTest("AtropManyChirals.sdf", true, 20, 20),
MolTest("BMS-986142.sdf", true, 42, 47),
MolTest("BMS-986142_3d_chiral.sdf", true, 72, 77),
MolTest("BMS-986142_3d.sdf", true, 72, 77),
MolTest("BMS-986142_atrop1.sdf", true, 42, 47),
MolTest("BMS-986142_atrop2.sdf", true, 42, 47),
MolTest("BMS-986142_atrop3.sdf", true, 42, 47),
MolTest("BMS-986142_atrop4.sdf", true, 42, 47),
MolTest("BMS-986142_atrop5.sdf", true, 42, 47),
MolTest("BMS-986142_atrop6.sdf", true, 42, 47),
MolTest("BMS-986142_atrop7.sdf", true, 42, 47),
MolTest("BMS-986142_atrop8.sdf", true, 42, 47),
MolTest("BMS-986142_atropBad2.sdf", true, 42, 47),
MolTest("JDQ443.sdf", true, 38, 44),
MolTest("JDQ443_3d.sdf", true, 66, 72),
MolTest("JDQ443_atrop1.sdf", true, 38, 44),
MolTest("JDQ443_atrop2.sdf", true, 38, 44),
MolTest("JDQ443_atrop3.sdf", true, 38, 44),
MolTest("JDQ443_atropBad1.sdf", true, 38, 44),
MolTest("RP-6306.sdf", true, 24, 26),
MolTest("RP-6306_atrop1.sdf", true, 24, 26),
MolTest("RP-6306_atrop2.sdf", true, 24, 26),
MolTest("RP-6306_atrop3.sdf", true, 24, 26),
MolTest("RP-6306_atrop4.sdf", true, 24, 26),
MolTest("RP-6306_atrop5.sdf", true, 24, 26),
MolTest("RP-6306_atropBad1.sdf", true, 24, 26),
MolTest("RP-6306_atropBad2.sdf", true, 24, 26),
// note the rp-6306_3d.sdf is backwards from the 2D versions
// the 2D version were based on images from drug hunter
// the 3D version came from PUBCHEM
MolTest("RP-6306_3d.sdf", true, 44, 46),
MolTest("Sotorasib.sdf", true, 41, 45),
MolTest("Sotorasib_atrop1.sdf", true, 41, 45),
MolTest("Sotorasib_atrop2.sdf", true, 41, 45),
MolTest("Sotorasib_atrop3.sdf", true, 41, 45),
MolTest("Sotorasib_atrop4.sdf", true, 41, 45),
MolTest("Sotorasib_atrop5.sdf", true, 41, 45),
MolTest("Sotorasib_atropBad1.sdf", true, 41, 45),
MolTest("Sotorasib_atropBad2.sdf", true, 41, 45),
// note the sotorasib_3d.sdf is backwards from the 2D versions
// the 2D version were based on images from drug hunter
// the 3D version came from PUBCHEM
MolTest("Sotorasib_3d.sdf", true, 71, 75),
MolTest("ZM374979.sdf", true, 45, 49),
MolTest("ZM374979_atrop1.sdf", true, 45, 49),
MolTest("ZM374979_atrop2.sdf", true, 45, 49),
MolTest("ZM374979_atrop3.sdf", true, 45, 49),
MolTest("ZM374979_atropBad1.sdf", true, 45, 49),
MolTest("Mrtx1719.sdf", true, 33, 37),
// note the Mrtx1719_3d.sdf is backwards from the 2D versions
// the 2D version were based on images from drug hunter
// the 3D version came from PUBCHEM
MolTest("Mrtx1719_3d.sdf", true, 51, 55),
MolTest("Mrtx1719_atrop1.sdf", true, 33, 37),
MolTest("Mrtx1719_atrop2.sdf", true, 33, 37),
MolTest("Mrtx1719_atrop3.sdf", true, 33, 37),
MolTest("Mrtx1719_atropBad1.sdf", true, 33, 37),
// macrocycles
MolTest("macrocycle-9-meta-wedge.sdf", true, 24, 26),
MolTest("macrocycle-9-ortho-wedge.sdf", true, 24, 26),
MolTest("macrocycle-8-meta-wedge.sdf", true, 23, 25),
MolTest("macrocycle-8-ortho-wedge.sdf", true, 23, 25),
MolTest("macrocycle-7-meta-wedge.sdf", true, 22, 24),
MolTest("macrocycle-7-ortho-wedge.sdf", true, 22, 24),
MolTest("macrocycle-6-meta-wedge.sdf", true, 21, 23),
MolTest("macrocycle-6-ortho-wedge.sdf", true, 21, 23),
MolTest("macrocycle-5-meta-wedge.sdf", true, 20, 22),
MolTest("macrocycle-5-ortho-wedge.sdf", true, 20, 22),
MolTest("macrocycle-9-meta-Cl-ortho-wedge.sdf", true, 25, 27),
MolTest("macrocycle-8-meta-Cl-ortho-wedge.sdf", true, 24, 26),
MolTest("macrocycle-7-meta-Cl-ortho-wedge.sdf", true, 23, 25),
MolTest("macrocycle-6-meta-Cl-ortho-wedge.sdf", true, 22, 24),
MolTest("macrocycle-5-meta-Cl-ortho-wedge.sdf", true, 21, 23),
MolTest("macrocycle-9-meta-broken-wedge.sdf", true, 24, 25),
MolTest("macrocycle-9-ortho-broken-wedge.sdf", true, 24, 25),
MolTest("macrocycle-8-meta-broken-wedge.sdf", true, 23, 24),
MolTest("macrocycle-8-ortho-broken-wedge.sdf", true, 23, 24),
MolTest("macrocycle-7-meta-broken-wedge.sdf", true, 22, 23),
MolTest("macrocycle-7-ortho-broken-wedge.sdf", true, 22, 23),
MolTest("macrocycle-6-meta-broken-wedge.sdf", true, 21, 22),
MolTest("macrocycle-6-ortho-broken-wedge.sdf", true, 21, 22),
MolTest("macrocycle-5-meta-broken-wedge.sdf", true, 20, 21),
MolTest("macrocycle-5-ortho-broken-wedge.sdf", true, 20, 21),
MolTest("macrocycle-9-meta-hash.sdf", true, 24, 26),
MolTest("macrocycle-9-ortho-hash.sdf", true, 24, 26),
MolTest("macrocycle-8-meta-hash.sdf", true, 23, 25),
MolTest("macrocycle-8-ortho-hash.sdf", true, 23, 25),
MolTest("macrocycle-7-meta-hash.sdf", true, 22, 24),
MolTest("macrocycle-7-ortho-hash.sdf", true, 22, 24),
MolTest("macrocycle-6-meta-hash.sdf", true, 21, 23),
MolTest("macrocycle-6-ortho-hash.sdf", true, 21, 23),
MolTest("macrocycle-5-meta-hash.sdf", true, 20, 22),
MolTest("macrocycle-5-ortho-hash.sdf", true, 20, 22),
MolTest("macrocycle-9-meta-Cl-ortho-hash.sdf", true, 25, 27),
MolTest("macrocycle-8-meta-Cl-ortho-hash.sdf", true, 24, 26),
MolTest("macrocycle-7-meta-Cl-ortho-hash.sdf", true, 23, 25),
MolTest("macrocycle-6-meta-Cl-ortho-hash.sdf", true, 22, 24),
MolTest("macrocycle-5-meta-Cl-ortho-hash.sdf", true, 21, 23),
MolTest("macrocycle-9-meta-broken-hash.sdf", true, 24, 25),
MolTest("macrocycle-9-ortho-broken-hash.sdf", true, 24, 25),
MolTest("macrocycle-8-meta-broken-hash.sdf", true, 23, 24),
MolTest("macrocycle-8-ortho-broken-hash.sdf", true, 23, 24),
MolTest("macrocycle-7-meta-broken-hash.sdf", true, 22, 23),
MolTest("macrocycle-7-ortho-broken-hash.sdf", true, 22, 23),
MolTest("macrocycle-6-meta-broken-hash.sdf", true, 21, 22),
MolTest("macrocycle-6-ortho-broken-hash.sdf", true, 21, 22),
MolTest("macrocycle-5-meta-broken-hash.sdf", true, 20, 21),
MolTest("macrocycle-5-ortho-broken-hash.sdf", true, 20, 21),
};
for (auto sdfTest : sdfTests) {
BOOST_LOG(rdInfoLog) << "Test: " << sdfTest.fileName << std::endl;
testMolFiles(&sdfTest);
}
}
}
};
void testLookForAtropisomersInSDdfFiles(std::string fileName,
unsigned int expectedHits,
unsigned int expectedMisses) {
BOOST_LOG(rdInfoLog) << "Looking for atropisomers in " << fileName
<< std::endl;
std::string rdbase = getenv("RDBASE");
std::string fName =
rdbase + "/Code/GraphMol/FileParsers/test_data/atropisomers/" + fileName;
std::ifstream in;
in.open(fName);
std::string line;
unsigned int foundCount = 0;
unsigned int notFoundCount = 0;
while (!in.eof()) {
std::string molBlock = "";
while (std::getline(in, line)) {
if (line.find("$$$$") != std::string::npos) {
break;
}
molBlock += line + "\n";
}
if (molBlock.length() < 10) {
continue; // try for another;
}
std::unique_ptr<RWMol> mol(MolBlockToMol(molBlock, false, false, false));
TEST_ASSERT(mol != nullptr);
auto hasAtropisomers = RDKit::Atropisomers::doesMolHaveAtropisomers(*mol);
if (hasAtropisomers) {
BOOST_LOG(rdInfoLog) << "Found atropisomers in " << fileName << std::endl;
foundCount++;
printf("Atropisomers- %d hits %d misses\r", foundCount, notFoundCount);
std::flush(std::cout);
std::ofstream out;
out.open(fName + "_" + std::to_string(foundCount) + ".sdf");
out << molBlock << std::endl;
} else {
notFoundCount++;
if (notFoundCount % 100 == 0) {
printf("Atropisomers- %d hits %d misses\r", foundCount,
notFoundCount);
std::flush(std::cout);
}
}
}
printf("\nFinal results:\nFound atropisomers in %s - %d hits %d misses\n",
fileName.c_str(), foundCount, notFoundCount);
TEST_ASSERT(foundCount == expectedHits);
TEST_ASSERT(notFoundCount == expectedMisses);
}
int main(int argc, char *argv[]) {
(void)argc;
(void)argv;
RDLog::InitLogs();
boost::logging::enable_logs("rdApp.info");
BOOST_LOG(rdInfoLog) << " ---- Running with POSIX locale ----- " << std::endl;
MolAtropTest molAtropTest;
if (argc > 1) {
molAtropTest.testToRun = argv[1];
}
if (argc > 2 && std::string(argv[2]) == "generate") {
molAtropTest.generateExpectedFiles = true;
}
RDLog::InitLogs();
BOOST_LOG(rdInfoLog) << " ---- Running with POSIX locale ----- " << std::endl;
molAtropTest.RunTests();
testLookForAtropisomersInSDdfFiles("TestMultInSDF.sdf", 1, 4);
return 0;
}
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