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//
// Copyright 2020-2022 Schrodinger, Inc 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 <catch2/catch_all.hpp>
#include <GraphMol/RDKitBase.h>
#include <GraphMol/TautomerQuery/TautomerQuery.h>
#include <GraphMol/ROMol.h>
#include <GraphMol/SmilesParse/SmilesWrite.h>
#include <GraphMol/Substruct/SubstructMatch.h>
#include <GraphMol/Fingerprints/Fingerprints.h>
#include <DataStructs/BitOps.h>
#include <GraphMol/MolPickler.h>
#include <GraphMol/QueryOps.h>
#include <GraphMol/SmilesParse/SmilesParse.h>
// #define VERBOSE 1
using namespace RDKit;
TEST_CASE("TEMPLATE_ERROR") {
// for this guy the template needs to account for bonds modified when
// tautomers are sanitized
auto mol = "Cc1nc2ccccc2[nH]1"_smiles;
REQUIRE(mol);
auto target = "CN1C2=C(C(=O)Nc3ccccc3)C(=O)CCN2c2ccccc21"_smiles;
REQUIRE(target);
auto tautomerQuery =
std::unique_ptr<TautomerQuery>(TautomerQuery::fromMol(*mol));
auto match = false;
MatchVectType matchVect;
for (auto taut : tautomerQuery->getTautomers()) {
auto test = SubstructMatch(*target, *taut, matchVect);
#ifdef VERBOSE
std::cout << "Tautomer " << MolToSmiles(*taut) << " match " << test
<< std::endl;
#endif
if (test) {
match = true;
}
}
CHECK(match);
SubstructMatchParameters params;
std::vector<ROMOL_SPTR> matchingTautomers;
auto matches =
tautomerQuery->substructOf(*target, params, &matchingTautomers);
CHECK(matches.size() == 1);
REQUIRE(matchingTautomers.size() == 1);
}
TEST_CASE("TEST_UNIQUIFY") {
auto mol = "O=C1CCCCC1"_smiles;
REQUIRE(mol);
auto target = "O=C1CCCC(CC)C1"_smiles;
REQUIRE(target);
auto tautomerQuery =
std::unique_ptr<TautomerQuery>(TautomerQuery::fromMol(*mol));
auto tautomers = tautomerQuery->getTautomers();
SubstructMatchParameters params;
params.maxMatches = 1000;
std::vector<ROMOL_SPTR> matchingTautomers;
params.uniquify = true;
auto matches =
tautomerQuery->substructOf(*target, params, &matchingTautomers);
CHECK(matches.size() == 1);
REQUIRE(matchingTautomers.size() == 1);
params.uniquify = false;
matches = tautomerQuery->substructOf(*target, params, &matchingTautomers);
CHECK(matches.size() == 2);
REQUIRE(matchingTautomers.size() == 2);
CHECK(matchingTautomers[0] == matchingTautomers[1]);
}
TEST_CASE("DIFFERENT_TO_ENUMERATED") {
// test shows we need to set uniquify = false when matching template
auto mol = "NC(N)=O"_smiles;
auto tautomerQuery =
std::unique_ptr<TautomerQuery>(TautomerQuery::fromMol(*mol));
auto tautomers = tautomerQuery->getTautomers();
// auto target =
// "NC1=NC2(CO1)c1cc(-c3cccnc3F)ccc1Oc1cnc(C3=CCCOC3)cc12"_smiles;
auto target = "NC1=NCCO1"_smiles;
auto enumMatch = false;
MatchVectType matchVect;
for (auto t : tautomers) {
if (SubstructMatch(*target, *t, matchVect)) {
enumMatch = true;
break;
}
}
CHECK(enumMatch);
auto match = tautomerQuery->isSubstructOf(*target);
CHECK(match);
}
TEST_CASE("SIMPLE_ERROR") {
auto mol = "CC=O"_smiles;
REQUIRE(mol);
auto tautomerQuery =
std::unique_ptr<TautomerQuery>(TautomerQuery::fromMol(*mol));
auto target = "OC(C)=O"_smiles;
auto matches = SubstructMatch(*target, *mol);
CHECK(matches.size() == 1);
auto match = tautomerQuery->isSubstructOf(*target);
CHECK(match);
target = "CCN(CC)C(=O)COP(=O)(O)COCCn1cnc2c(N)ncnc21"_smiles;
match = tautomerQuery->isSubstructOf(*target);
CHECK(match);
}
TEST_CASE("TEST_ENOL") {
auto mol = "O=C1CCCCC1"_smiles;
REQUIRE(mol);
auto tautomerQuery =
std::unique_ptr<TautomerQuery>(TautomerQuery::fromMol(*mol));
auto tautomers = tautomerQuery->getTautomers();
CHECK(tautomers.size() == 2);
auto modifiedAtoms = tautomerQuery->getModifiedAtoms();
CHECK(modifiedAtoms.size() == 3);
auto modifiedBonds = tautomerQuery->getModifiedBonds();
CHECK(modifiedBonds.size() == 3);
auto target1 = "OC1=CCCC(CC)C1"_smiles;
REQUIRE(target1);
SubstructMatchParameters params;
std::vector<ROMOL_SPTR> matchingTautomers;
auto matches =
tautomerQuery->substructOf(*target1, params, &matchingTautomers);
CHECK(matches.size() == 1);
auto match = tautomerQuery->isSubstructOf(*target1, params);
CHECK(match);
REQUIRE(matchingTautomers.size() == 1);
auto tautomerSmiles = MolToSmiles(*matchingTautomers[0]);
CHECK(tautomerSmiles == "OC1=CCCCC1");
auto target2 = "O=C1CCCC(CC)C1"_smiles;
REQUIRE(target2);
matches = tautomerQuery->substructOf(*target2, params, &matchingTautomers);
CHECK(matches.size() == 1);
REQUIRE(matchingTautomers.size() == 1);
tautomerSmiles = MolToSmiles(*matchingTautomers[0]);
CHECK(tautomerSmiles == "O=C1CCCCC1");
MatchVectType matchVect;
auto hasMatch = SubstructMatch(*target1, *tautomerQuery, matchVect);
CHECK(hasMatch);
auto templateFingerpint = tautomerQuery->patternFingerprintTemplate();
REQUIRE(templateFingerpint);
auto target1Fingerprint = TautomerQuery::patternFingerprintTarget(*target1);
REQUIRE(target1Fingerprint);
CHECK(AllProbeBitsMatch(*templateFingerpint, *target1Fingerprint));
delete target1Fingerprint;
auto target2Fingerprint = TautomerQuery::patternFingerprintTarget(*target2);
REQUIRE(target2Fingerprint);
CHECK(AllProbeBitsMatch(*templateFingerpint, *target2Fingerprint));
delete target2Fingerprint;
delete templateFingerpint;
}
TEST_CASE("TEST_COMPLEX") {
auto mol = "Nc1nc(=O)c2nc[nH]c2[nH]1"_smiles;
REQUIRE(mol);
auto tautomerQuery =
std::unique_ptr<TautomerQuery>(TautomerQuery::fromMol(*mol));
CHECK(15 == tautomerQuery->getTautomers().size());
auto queryFingerprint = tautomerQuery->patternFingerprintTemplate();
REQUIRE(queryFingerprint);
std::vector<std::string> targetSmis{"CCc1nc2[nH]c(=N)nc(O)c2[nH]1",
"CN1C2=NC=NC2=C(O)N=C1N"};
for (auto targetSmiles : targetSmis) {
auto target = SmilesToMol(targetSmiles);
REQUIRE(target);
CHECK(tautomerQuery->isSubstructOf(*target));
auto targetFingerprint = TautomerQuery::patternFingerprintTarget(*target);
REQUIRE(targetFingerprint);
CHECK(AllProbeBitsMatch(*queryFingerprint, *targetFingerprint));
delete targetFingerprint;
delete target;
}
delete queryFingerprint;
}
TEST_CASE("TEST_PICKLE") {
auto mol = "O=C1CCCCC1"_smiles;
REQUIRE(mol);
auto tautomerQuery =
std::unique_ptr<TautomerQuery>(TautomerQuery::fromMol(*mol));
auto templateMol = tautomerQuery->getTemplateMolecule();
std::string pickle;
MolPickler::pickleMol(templateMol, pickle);
ROMol pickleMol;
MolPickler::molFromPickle(pickle, pickleMol);
for (auto modifiedBondIdx : tautomerQuery->getModifiedBonds()) {
auto modifiedBond = pickleMol.getBondWithIdx(modifiedBondIdx);
REQUIRE(modifiedBond->hasQuery());
CHECK(modifiedBond->getQuery()->getDescription() ==
"SingleOrDoubleOrAromaticBond");
}
}
TEST_CASE("TEST_FINGERPRINT") {
auto mol = "O=C1CCCCC1"_smiles;
REQUIRE(mol);
auto tautomerQuery =
std::unique_ptr<TautomerQuery>(TautomerQuery::fromMol(*mol));
auto templateMol = tautomerQuery->getTemplateMolecule();
// this test molecule has complex query bonds where the template has query
// bonds, but they are not identified as tautomer bonds.
RWMol molWithoutTautomerBonds(*mol);
std::vector<std::pair<int, int>> atomIndexes;
for (auto modifiedBondIdx : tautomerQuery->getModifiedBonds()) {
auto queryBond = new QueryBond();
queryBond->setQuery(makeBondOrderEqualsQuery(Bond::BondType::SINGLE));
queryBond->expandQuery(makeBondOrderEqualsQuery(Bond::BondType::AROMATIC),
Queries::COMPOSITE_OR);
molWithoutTautomerBonds.replaceBond(modifiedBondIdx, queryBond, true);
delete queryBond;
}
// The molecule without tautomer bonds has the same regular fingerprint as the
// template
#ifdef VERBOSE
std::cout << std::endl << "fingerprinting template" << std::endl;
#endif
auto templateQueryFingerprint = PatternFingerprintMol(templateMol);
#ifdef VERBOSE
std::cout << "fingerprinting mol without bonds" << std::endl;
#endif
auto molWithoutTautomerBondsFingerprint =
PatternFingerprintMol(molWithoutTautomerBonds);
REQUIRE(templateQueryFingerprint);
REQUIRE(molWithoutTautomerBondsFingerprint);
CHECK(AllProbeBitsMatch(*templateQueryFingerprint,
*molWithoutTautomerBondsFingerprint));
CHECK(AllProbeBitsMatch(*molWithoutTautomerBondsFingerprint,
*templateQueryFingerprint));
delete templateQueryFingerprint;
delete molWithoutTautomerBondsFingerprint;
// The tautomer fingerprint for the molecule without tautomer bonds has a
// subset of the template's tautomeric fingerprint.
templateQueryFingerprint = tautomerQuery->patternFingerprintTemplate();
molWithoutTautomerBondsFingerprint =
TautomerQuery::patternFingerprintTarget(molWithoutTautomerBonds);
REQUIRE(templateQueryFingerprint);
REQUIRE(molWithoutTautomerBondsFingerprint);
#ifdef VERBOSE
std::cout << std::endl << "molWithoutTautomerBonds" << std::endl;
std::vector<int> onBits;
molWithoutTautomerBondsFingerprint->getOnBits(onBits);
for (auto bit : onBits) {
std::cout << bit << " ";
}
std::cout << std::endl;
std::cout << std::endl << "template" << std::endl;
templateQueryFingerprint->getOnBits(onBits);
for (auto bit : onBits) {
std::cout << bit << " ";
}
std::cout << std::endl;
#endif
CHECK(AllProbeBitsMatch(*molWithoutTautomerBondsFingerprint,
*templateQueryFingerprint));
CHECK(!AllProbeBitsMatch(*templateQueryFingerprint,
*molWithoutTautomerBondsFingerprint));
// The tautomer fingerprint for the template is a subset of the tautomer
// fingerprint for the original molecule.
auto molFingerprint = TautomerQuery::patternFingerprintTarget(*mol);
CHECK(AllProbeBitsMatch(*templateQueryFingerprint, *molFingerprint));
// This expected bit count for the template tautomeric fingerprint applies for
// all queries if there are no bit clashes
auto expectedTemplateBitsCount =
molWithoutTautomerBondsFingerprint->getNumOnBits() +
(molFingerprint->getNumOnBits() -
molWithoutTautomerBondsFingerprint->getNumOnBits()) /
2;
CHECK(expectedTemplateBitsCount == templateQueryFingerprint->getNumOnBits());
delete templateQueryFingerprint;
delete molWithoutTautomerBondsFingerprint;
delete molFingerprint;
}
TEST_CASE("TEST_NOT_TAUTOMER") {
auto mol = "c1ccccc1"_smiles;
REQUIRE(mol);
auto tautomerQuery =
std::unique_ptr<TautomerQuery>(TautomerQuery::fromMol(*mol));
CHECK(1 == tautomerQuery->getTautomers().size());
CHECK(0 == tautomerQuery->getModifiedAtoms().size());
CHECK(0 == tautomerQuery->getModifiedBonds().size());
auto target = "CC1=NC2=CC=CC=C2O1"_smiles;
REQUIRE(target);
CHECK(tautomerQuery->isSubstructOf(*target));
}
TEST_CASE("github #3821 TAUTOMERQUERY_COPY_CONSTRUCTOR") {
auto mol = "c1ccccc1"_smiles;
auto tautomerQuery =
std::unique_ptr<TautomerQuery>(TautomerQuery::fromMol(*mol));
auto tautomerQueryCopyConstructed =
std::unique_ptr<TautomerQuery>(new TautomerQuery(*tautomerQuery));
CHECK(&(tautomerQuery->getTemplateMolecule()) !=
&tautomerQueryCopyConstructed->getTemplateMolecule());
}
TEST_CASE("github #3821 check TAUTOMERQUERY_OPERATOR= does a deep copy") {
auto mol = "c1ccccc1"_smiles;
auto tautomerQuery =
std::unique_ptr<TautomerQuery>(TautomerQuery::fromMol(*mol));
auto tautomerQueryAssigned = *tautomerQuery;
CHECK(&(tautomerQuery->getTemplateMolecule()) !=
&tautomerQueryAssigned.getTemplateMolecule());
}
TEST_CASE("Serialization") {
#ifdef RDK_USE_BOOST_SERIALIZATION
SECTION("basics") {
auto mol = "Nc1nc(=O)c2nc[nH]c2[nH]1"_smiles;
REQUIRE(mol);
auto tautomerQuery =
std::unique_ptr<TautomerQuery>(TautomerQuery::fromMol(*mol));
CHECK(15 == tautomerQuery->getTautomers().size());
std::string pickle = tautomerQuery->serialize();
TautomerQuery serialized(pickle);
CHECK(serialized.getTautomers().size() ==
tautomerQuery->getTautomers().size());
auto queryFingerprint = serialized.patternFingerprintTemplate();
REQUIRE(queryFingerprint);
std::vector<std::string> targetSmis{"CCc1nc2[nH]c(=N)nc(O)c2[nH]1",
"CN1C2=NC=NC2=C(O)N=C1N"};
for (auto targetSmiles : targetSmis) {
auto target = SmilesToMol(targetSmiles);
REQUIRE(target);
CHECK(serialized.isSubstructOf(*target));
auto targetFingerprint = TautomerQuery::patternFingerprintTarget(*target);
REQUIRE(targetFingerprint);
CHECK(AllProbeBitsMatch(*queryFingerprint, *targetFingerprint));
delete targetFingerprint;
delete target;
}
delete queryFingerprint;
}
#endif
}
TEST_CASE("Tautomer queries should propagate atom properties") {
auto mol = "COC1=NNC(*)=C1"_smiles;
REQUIRE(mol);
mol->getAtomWithIdx(6)->setProp("_foo", 6);
auto tq = std::unique_ptr<TautomerQuery>(TautomerQuery::fromMol(*mol));
CHECK(tq->getTautomers()[0]->getAtomWithIdx(6)->hasProp("_foo"));
CHECK(tq->getTautomers()[1]->getAtomWithIdx(6)->hasProp("_foo"));
CHECK(tq->getTemplateMolecule().getAtomWithIdx(6)->hasProp("_foo"));
#ifdef RDK_USE_BOOST_SERIALIZATION
SECTION("serialization") {
TautomerQuery tq2(tq->serialize());
CHECK(tq2.getTautomers()[0]->getAtomWithIdx(6)->hasProp("_foo"));
CHECK(tq2.getTautomers()[1]->getAtomWithIdx(6)->hasProp("_foo"));
CHECK(tq2.getTemplateMolecule().getAtomWithIdx(6)->hasProp("_foo"));
}
#endif
}
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