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rdkit/Code/GraphMol/RGroupDecomposition/testRGroupDecomp.cpp
Greg Landrum 9367e207d5 remove some warnings with -Wextra (#7339)
2024-04-11 11:01:59 +02:00

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// Copyright (c) 2017, Novartis Institutes for BioMedical Research Inc.
// All rights reserved.
//
// Redistribution and use in source and binary forms, with or without
// modification, are permitted provided that the following conditions are
// met:
//
// * Redistributions of source code must retain the above copyright
// notice, this list of conditions and the following disclaimer.
// * Redistributions in binary form must reproduce the above
// copyright notice, this list of conditions and the following
// disclaimer in the documentation and/or other materials provided
// with the distribution.
// * Neither the name of Novartis Institutes for BioMedical Research Inc.
// nor the names of its contributors may be used to endorse or promote
// products derived from this software without specific prior written
// permission.
//
// THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS
// "AS IS" AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT
// LIMITED TO, THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR
// A PARTICULAR PURPOSE ARE DISCLAIMED. IN NO EVENT SHALL THE COPYRIGHT
// OWNER OR CONTRIBUTORS BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL,
// SPECIAL, EXEMPLARY, OR CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT
// LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES; LOSS OF USE,
// DATA, OR PROFITS; OR BUSINESS INTERRUPTION) HOWEVER CAUSED AND ON ANY
// THEORY OF LIABILITY, WHETHER IN CONTRACT, STRICT LIABILITY, OR TORT
// (INCLUDING NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE
// OF THIS SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.
//
#include <RDGeneral/test.h>
#include <RDGeneral/RDLog.h>
#include <RDGeneral/utils.h>
#include <GraphMol/RDKitBase.h>
#include <string>
#include <iostream>
#include <GraphMol/SmilesParse/SmilesParse.h>
#include <GraphMol/SmilesParse/SmilesWrite.h>
#include <GraphMol/ChemTransforms/ChemTransforms.h>
#include <GraphMol/RGroupDecomposition/RGroupDecomp.h>
#include <GraphMol/RGroupDecomposition/RGroupDecompData.h>
#include <GraphMol/RGroupDecomposition/RGroupUtils.h>
#include <GraphMol/FileParsers/FileParsers.h>
#include <GraphMol/FileParsers/MolSupplier.h>
#include <RDGeneral/Exceptions.h>
#include <boost/tokenizer.hpp>
#include <regex>
// #define DEBUG
typedef boost::tokenizer<boost::char_separator<char>> tokenizer;
using namespace RDKit;
#ifdef DEBUG
const bool DOASSERT = false;
#else
const bool DOASSERT = true;
#endif
typedef std::vector<std::unique_ptr<ROMol>> UMOLS;
#define UPTR(m) std::unique_ptr<ROMol>(m)
void CHECK_RGROUP(RGroupRows::const_iterator &it, const std::string &expected,
ROMol *mol = nullptr, bool doassert = DOASSERT) {
std::ostringstream str;
int i = 0;
std::unique_ptr<ROMol> res;
for (auto rgroups = it->begin(); rgroups != it->end(); ++rgroups, ++i) {
if (i) {
str << " ";
if (mol) {
res = molzip(*res, *rgroups->second.get());
}
} else if (mol) {
res = std::unique_ptr<ROMol>(new ROMol(*rgroups->second.get()));
}
// rlabel:smiles
str << rgroups->first << ":" << MolToSmiles(*rgroups->second.get());
}
std::string result = str.str();
if (expected != result) {
std::cerr << "Expected: '" << expected << "'" << std::endl;
std::cerr << "Got: '" << result << "'" << std::endl;
}
if (doassert) {
TEST_ASSERT(result == expected)
if (mol) {
auto smi1 = MolToSmiles(*res);
auto smi2 = MolToSmiles(*mol);
TEST_ASSERT(smi1 == smi2)
}
}
}
void DUMP_RGROUP(RGroupRows::const_iterator &it, std::string &result) {
std::ostringstream str;
for (const auto &rgroups : *it) {
// rlabel:smiles
str << rgroups.first << ":" << MolToSmiles(*rgroups.second.get(), true)
<< " ";
}
std::cerr << str.str() << std::endl;
result = str.str();
}
const char *symdata[5] = {"c1(Cl)ccccc1", "c1c(Cl)cccc1", "c1cccc(Cl)c1",
"c1cc(Cl)ccc1", "c1ccc(Cl)cc1"};
void testSymmetryMatching(RGroupScore scoreMethod = Match) {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog)
<< "test rgroup decomp symmetry matching with score method "
<< scoreMethod << std::endl;
UMOLS mols;
RWMol *core = SmilesToMol("c1ccccc1");
RGroupDecompositionParameters params;
params.scoreMethod = scoreMethod;
RGroupDecomposition decomp(*core, params);
for (int i = 0; i < 5; ++i) {
ROMol *mol = SmilesToMol(symdata[i]);
int res = decomp.add(*mol);
TEST_ASSERT(res == i);
mols.push_back(UPTR(mol));
}
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
// All Cl's should be labeled with the same rgroup
int i = 0;
for (RGroupRows::const_iterator it = rows.begin(); it != rows.end();
++it, ++i) {
CHECK_RGROUP(it, "Core:c1ccc([*:1])cc1 R1:Cl[*:1]", mols[i].get());
}
delete core;
}
void testGaSymmetryMatching(RGroupScore scoreMethod) {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog)
<< "test rgroup decomp symmetry matching using GA with scoring method "
<< scoreMethod << std::endl;
UMOLS mols;
RWMol *core = SmilesToMol("c1ccccc1");
RGroupDecompositionParameters params;
params.matchingStrategy = GA;
params.scoreMethod = scoreMethod;
RGroupDecomposition decomp(*core, params);
for (int i = 0; i < 5; ++i) {
ROMol *mol = SmilesToMol(symdata[i]);
int res = decomp.add(*mol);
TEST_ASSERT(res == i);
mols.push_back(UPTR(mol));
}
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
// All Cl's should be labeled with the same rgroup
int i = 0;
for (RGroupRows::const_iterator it = rows.begin(); it != rows.end();
++it, ++i) {
CHECK_RGROUP(it, "Core:c1ccc([*:1])cc1 R1:Cl[*:1]", mols[i].get());
}
delete core;
}
void testGaBatch() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog)
<< "test rgroup decomp symmetry matching using GA with parallel runs"
<< std::endl;
UMOLS mols;
RWMol *core = SmilesToMol("c1ccccc1");
RGroupDecompositionParameters params;
params.matchingStrategy = GA;
params.scoreMethod = FingerprintVariance;
params.gaNumberRuns = 3;
params.gaParallelRuns = true;
std::stringstream sstrm;
rdWarningLog->SetTee(sstrm);
RGroupDecomposition decomp(*core, params);
for (int i = 0; i < 5; ++i) {
ROMol *mol = SmilesToMol(symdata[i]);
int res = decomp.add(*mol);
TEST_ASSERT(res == i);
mols.push_back(UPTR(mol));
}
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
bool isParallelGaEnabled =
(sstrm.str().find("This RDKit build does not enable GA parallel runs") ==
std::string::npos);
#ifdef RDK_TEST_MULTITHREADED
TEST_ASSERT(isParallelGaEnabled);
#else
TEST_ASSERT(!isParallelGaEnabled);
#endif
rdWarningLog->ClearTee();
// All Cl's should be labeled with the same rgroup
int i = 0;
for (RGroupRows::const_iterator it = rows.begin(); it != rows.end(); ++it) {
CHECK_RGROUP(it, "Core:c1ccc([*:1])cc1 R1:Cl[*:1]", mols[i].get());
}
delete core;
}
const char *matchRGroupOnlyData[] = {
"c1(Cl)ccccc1", "c1c(Cl)cccc1", "c1cc(Cl)ccc1",
"c1ccc(Cl)cc1", "c1c(Cl)cccc(I)1",
};
void testRGroupOnlyMatching() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "test rgroup decomp rgroup only matching"
<< std::endl;
UMOLS mols;
RWMol *core = SmilesToMol("c1ccccc1[1*]");
RGroupDecompositionParameters params;
params.labels = IsotopeLabels;
params.onlyMatchAtRGroups = true;
RGroupDecomposition decomp(*core, params);
for (int i = 0; i < 5; ++i) {
ROMol *mol = SmilesToMol(matchRGroupOnlyData[i]);
int res = decomp.add(*mol);
if (i < 4) {
TEST_ASSERT(res == i);
mols.push_back(UPTR(mol));
} else {
TEST_ASSERT(res == -1);
delete mol;
}
}
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
// All Cl's should be labeled with the same rgroup
int i = 0;
for (RGroupRows::const_iterator it = rows.begin(); it != rows.end();
++it, ++i) {
CHECK_RGROUP(it, "Core:c1ccc([*:1])cc1 R1:Cl[*:1]", mols[i].get());
}
delete core;
}
const char *ringData[3] = {"c1cocc1", "c1c[nH]cc1", "c1cscc1"};
const char *ringDataRes[3] = {"Core:c1ccoc1", "Core:c1cc[nH]c1",
"Core:c1ccsc1"};
void testRingMatching() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "test rgroup decomp ring matching" << std::endl;
UMOLS mols;
RWMol *core = SmilesToMol("c1ccc[1*]1");
RGroupDecompositionParameters params;
params.labels = IsotopeLabels;
auto exceptionThrown = false;
try {
RGroupDecomposition decompError(*core, params);
} catch (ValueErrorException &) {
exceptionThrown = true;
}
TEST_ASSERT(exceptionThrown);
params.allowNonTerminalRGroups = true;
RGroupDecomposition decomp(*core, params);
for (int i = 0; i < 3; ++i) {
ROMol *mol = SmilesToMol(ringData[i]);
int res = decomp.add(*mol);
TEST_ASSERT(res == i);
mols.push_back(UPTR(mol));
}
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
auto cols = decomp.getRGroupsAsColumns();
// All Cl's should be labeled with the same rgroup
int i = 0;
for (RGroupRows::const_iterator it = rows.begin(); it != rows.end();
++it, ++i) {
// Ring rgroups not supported by molzip yet.
CHECK_RGROUP(it, ringDataRes[i]);
}
delete core;
}
const char *ringData2[3] = {"c1cocc1CCl", "c1c[nH]cc1CI", "c1cscc1CF"};
const char *ringDataRes2[3] = {"Core:c1cc(C[*:2])co1 R2:Cl[*:2]",
"Core:c1cc(C[*:2])c[nH]1 R2:I[*:2]",
"Core:c1cc(C[*:2])cs1 R2:F[*:2]"};
void testRingMatching2() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "test rgroup decomp full ring dummy core"
<< std::endl;
RWMol *core = SmartsToMol("*1***[*:1]1C[*:2]");
RGroupDecompositionParameters params;
params.allowNonTerminalRGroups = true;
RGroupDecomposition decomp(*core, params);
for (int i = 0; i < 3; ++i) {
ROMol *mol = SmilesToMol(ringData2[i]);
int res = decomp.add(*mol);
TEST_ASSERT(res == i);
delete mol;
}
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
// All Cl's should be labeled with the same rgroup
int i = 0;
for (RGroupRows::const_iterator it = rows.begin(); it != rows.end();
++it, ++i) {
CHECK_RGROUP(it, ringDataRes2[i]);
}
delete core;
}
const char *ringData3[3] = {"c1cocc1CCl", "c1c[nH]cc1CI", "c1cscc1CF"};
const char *ringDataRes3[3] = {"Core:c1cc([*:1])co1 R1:ClC[*:1]",
"Core:c1cc([*:1])c[nH]1 R1:IC[*:1]",
"Core:c1cc([*:1])cs1 R1:FC[*:1]"};
void testRingMatching3() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "test rgroup decomp full ring dummy core"
<< std::endl;
RWMol *core = SmartsToMol("*1***[*:1]1");
// RWMol *core = SmartsToMol("*1****1");
std::vector<RGroupScore> matchtypes{Match, FingerprintVariance};
for (auto match : matchtypes) {
RGroupDecompositionParameters params;
// This test is currently failing using the default scoring method (the
// halogens are not all in the same group)
params.scoreMethod = match;
params.allowNonTerminalRGroups = true;
RGroupDecomposition decomp(*core, params);
for (int i = 0; i < 3; ++i) {
ROMol *mol = SmilesToMol(ringData3[i]);
int res = decomp.add(*mol);
delete mol;
TEST_ASSERT(res == i);
}
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
// All Cl's should be labeled with the same rgroup
int i = 0;
for (RGroupRows::const_iterator it = rows.begin(); it != rows.end();
++it, ++i) {
CHECK_RGROUP(it, ringDataRes3[i]);
}
}
delete core;
}
const char *coreSmi[] = {
"C1CCNC(Cl)CC1", "C1CC(Cl)NCCC1", "C1CCNC(I)CC1", "C1CC(I)NCCC1",
"C1CCSC(Cl)CC1", "C1CC(Cl)SCCC1", "C1CCSC(I)CC1", "C1CC(I)SCCC1",
"C1CCOC(Cl)CC1", "C1CC(Cl)OCCC1", "C1CCOC(I)CC1", "C1CC(I)OCCC1"};
const char *coreSmiRes[] = {
"Core:C1CCNC([*:1])CC1 R1:Cl[*:1]", "Core:C1CCNC([*:1])CC1 R1:Cl[*:1]",
"Core:C1CCNC([*:1])CC1 R1:I[*:1]", "Core:C1CCNC([*:1])CC1 R1:I[*:1]",
"Core:C1CCSC([*:1])CC1 R1:Cl[*:1]", "Core:C1CCSC([*:1])CC1 R1:Cl[*:1]",
"Core:C1CCSC([*:1])CC1 R1:I[*:1]", "Core:C1CCSC([*:1])CC1 R1:I[*:1]",
"Core:C1CCOC([*:1])CC1 R1:Cl[*:1]", "Core:C1CCOC([*:1])CC1 R1:Cl[*:1]",
"Core:C1CCOC([*:1])CC1 R1:I[*:1]", "Core:C1CCOC([*:1])CC1 R1:I[*:1]"};
void testMultiCore() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "test multi core" << std::endl;
std::vector<ROMOL_SPTR> cores;
cores.emplace_back(SmartsToMol("C1CCNCCC1"));
cores.emplace_back(SmilesToMol("C1CCOCCC1"));
cores.emplace_back(SmilesToMol("C1CCSCCC1"));
UMOLS mols;
RGroupDecomposition decomp(cores);
for (unsigned int i = 0; i < sizeof(coreSmi) / sizeof(const char *); ++i) {
ROMol *mol = SmilesToMol(coreSmi[i]);
unsigned int res = decomp.add(*mol);
mols.push_back(UPTR(mol));
TEST_ASSERT(res == i);
}
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
// All Cl's should be labeled with the same rgroup
int i = 0;
for (RGroupRows::const_iterator it = rows.begin(); it != rows.end();
++it, ++i) {
// molzip doesn't support double attachments yet (it probably should)
CHECK_RGROUP(it, coreSmiRes[i]);
}
}
void testGithub1550() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog)
<< "test Github #1550: Kekulization error from R-group decomposition"
<< std::endl;
RWMol *core = SmilesToMol("O=c1oc2ccccc2cc1");
RGroupDecompositionParameters params;
RGroupDecomposition decomp(*core, params);
const char *smilesData[3] = {"O=c1cc(Cn2ccnc2)c2ccc(Oc3ccccc3)cc2o1",
"O=c1oc2ccccc2c(Cn2ccnc2)c1-c1ccccc1",
"COc1ccc2c(Cn3cncn3)cc(=O)oc2c1"};
for (int i = 0; i < 3; ++i) {
ROMol *mol = SmilesToMol(smilesData[i]);
int res = decomp.add(*mol);
delete mol;
TEST_ASSERT(res == i);
}
decomp.process();
RGroupColumns groups = decomp.getRGroupsAsColumns();
RWMol *coreRes = (RWMol *)groups["Core"][0].get();
TEST_ASSERT(coreRes->getNumAtoms() == 14);
MolOps::Kekulize(*coreRes);
RWMol *rg2 = (RWMol *)groups["R2"][0].get();
TEST_ASSERT(rg2->getNumAtoms() == 7);
MolOps::Kekulize(*rg2);
delete core;
}
void testRemoveHs() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "test remove sidechain Hs" << std::endl;
RWMol *core = SmilesToMol("O=c1oc2ccccc2cc1");
{
RGroupDecompositionParameters params;
RGroupDecomposition decomp(*core, params);
const char *smilesData[3] = {"O=c1cc(Cn2ccnc2)c2ccc(Oc3ccccc3)cc2o1",
"O=c1oc2ccccc2c(Cn2ccnc2)c1-c1ccccc1",
"COc1ccc2c(Cn3cncn3)cc(=O)oc2c1"};
for (int i = 0; i < 3; ++i) {
ROMol *mol = SmilesToMol(smilesData[i]);
int res = decomp.add(*mol);
delete mol;
TEST_ASSERT(res == i);
}
decomp.process();
RGroupColumns groups = decomp.getRGroupsAsColumns();
RWMol *rg2 = (RWMol *)groups["R2"][0].get();
TEST_ASSERT(rg2->getNumAtoms() == 7);
}
{
RGroupDecompositionParameters params;
params.removeHydrogensPostMatch = false;
RGroupDecomposition decomp(*core, params);
const char *smilesData[3] = {"O=c1cc(Cn2ccnc2)c2ccc(Oc3ccccc3)cc2o1",
"O=c1oc2ccccc2c(Cn2ccnc2)c1-c1ccccc1",
"COc1ccc2c(Cn3cncn3)cc(=O)oc2c1"};
for (int i = 0; i < 3; ++i) {
ROMol *mol = SmilesToMol(smilesData[i]);
int res = decomp.add(*mol);
delete mol;
TEST_ASSERT(res == i);
}
decomp.process();
RGroupColumns groups = decomp.getRGroupsAsColumns();
RWMol *rg2 = (RWMol *)groups["R2"][0].get();
TEST_ASSERT(rg2->getNumAtoms() == 12);
}
delete core;
}
void testGitHubIssue1705() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog)
<< "test grouping substituents in chunks as large as possible"
<< std::endl;
#if 1
{
RWMol *core = SmilesToMol("Oc1ccccc1");
RGroupDecompositionParameters params;
RGroupDecomposition decomp(*core, params);
const char *smilesData[5] = {"Oc1ccccc1", "Oc1c(F)cccc1", "Oc1ccccc1F",
"Oc1c(F)cc(N)cc1", "Oc1ccccc1Cl"};
for (int i = 0; i < 5; ++i) {
ROMol *mol = SmilesToMol(smilesData[i]);
int res = decomp.add(*mol);
delete mol;
TEST_ASSERT(res == i);
}
decomp.process();
std::stringstream ss;
RGroupColumns groups = decomp.getRGroupsAsColumns();
for (auto &column : groups) {
ss << "Rgroup===" << column.first << std::endl;
for (auto &rgroup : column.second) {
ss << MolToSmiles(*rgroup) << std::endl;
}
}
delete core;
std::string expected = R"RES(Rgroup===Core
Oc1ccc([*:1])cc1[*:2]
Oc1ccc([*:1])cc1[*:2]
Oc1ccc([*:1])cc1[*:2]
Oc1ccc([*:1])cc1[*:2]
Oc1ccc([*:1])cc1[*:2]
Rgroup===R1
[H][*:1]
[H][*:1]
[H][*:1]
N[*:1]
[H][*:1]
Rgroup===R2
[H][*:2]
F[*:2]
F[*:2]
F[*:2]
Cl[*:2]
)RES";
#ifdef DEBUG
if (ss.str() != expected) {
std::cerr << __LINE__ << " ERROR got\n"
<< ss.str() << "\nexpected\n"
<< expected << std::endl;
}
#else
TEST_ASSERT(ss.str() == expected);
#endif
}
#endif
// std::cerr<<"n\n\n\n\n\n--------------------------------------------------------------\n\n\n\n\n";
{
RWMol *core = SmilesToMol("Cc1ccccc1");
RGroupDecompositionParameters params;
RGroupDecomposition decomp(*core, params);
std::vector<std::string> smilesData = {"c1ccccc1C", "Fc1ccccc1C",
"c1cccc(F)c1C", "Fc1cccc(F)c1C"};
for (const auto &smi : smilesData) {
ROMol *mol = SmilesToMol(smi);
decomp.add(*mol);
delete mol;
}
decomp.process();
std::stringstream ss;
RGroupColumns groups = decomp.getRGroupsAsColumns();
for (auto &column : groups) {
ss << "Rgroup===" << column.first << std::endl;
for (auto &rgroup : column.second) {
ss << MolToSmiles(*rgroup) << std::endl;
}
}
delete core;
std::string expected = R"RES(Rgroup===Core
Cc1c([*:1])cccc1[*:2]
Cc1c([*:1])cccc1[*:2]
Cc1c([*:1])cccc1[*:2]
Cc1c([*:1])cccc1[*:2]
Rgroup===R1
[H][*:1]
[H][*:1]
[H][*:1]
F[*:1]
Rgroup===R2
[H][*:2]
F[*:2]
F[*:2]
F[*:2]
)RES";
#ifdef DEBUG
if (ss.str() != expected) {
std::cerr << __LINE__ << " ERROR got\n"
<< ss.str() << "\nexpected\n"
<< expected << std::endl;
}
#else
TEST_ASSERT(ss.str() == expected);
#endif
}
}
void testMatchOnlyAtRgroupHs() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "test matching only rgroups but allows Hs"
<< std::endl;
RWMol *core = SmilesToMol("*OCC");
RGroupDecompositionParameters params;
params.onlyMatchAtRGroups = true;
RGroupDecomposition decomp(*core, params);
const char *smilesData[2] = {"OCC", "COCC"};
for (auto &i : smilesData) {
ROMol *mol = SmilesToMol(i);
decomp.add(*mol);
delete mol;
}
decomp.process();
std::stringstream ss;
RGroupColumns groups = decomp.getRGroupsAsColumns();
for (auto &column : groups) {
ss << "Rgroup===" << column.first << std::endl;
for (auto &rgroup : column.second) {
ss << MolToSmiles(*rgroup) << std::endl;
}
}
delete core;
TEST_ASSERT(
ss.str() ==
"Rgroup===Core\nCCO[*:1]\nCCO[*:1]\nRgroup===R1\n[H][*:1]\nC[*:1]\n");
}
void testGithub2332() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "test github #2332: RGroupDecomposition: addHs() "
"call should set coords "
<< std::endl;
auto core = "*OCC"_smiles;
RGroupDecompositionParameters params;
params.onlyMatchAtRGroups = true;
RGroupDecomposition decomp(*core, params);
std::string chains[2] = {
R"CTAB(
Mrv1810 03291913362D
4 3 0 0 0 0 999 V2000
2.0625 -0.7145 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0
1.2375 -0.7145 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
0.8250 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.0000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0 0 0 0
2 3 1 0 0 0 0
3 4 1 0 0 0 0
M END
)CTAB",
R"CTAB(
Mrv1810 03291913362D
3 2 0 0 0 0 999 V2000
1.2375 -0.7145 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
0.8250 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.0000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0 0 0 0
2 3 1 0 0 0 0
M END
)CTAB"};
for (const auto &chain : chains) {
ROMol *mol = MolBlockToMol(chain);
decomp.add(*mol);
delete mol;
}
decomp.process();
std::stringstream ss;
RGroupColumns groups = decomp.getRGroupsAsColumns();
auto &r1 = groups["R1"];
TEST_ASSERT(r1.size() == 2);
TEST_ASSERT(r1[1]->getAtomWithIdx(0)->getAtomicNum() == 1);
auto conf = r1[1]->getConformer();
TEST_ASSERT(!feq(conf.getAtomPos(0).x, 0.0));
TEST_ASSERT(!feq(conf.getAtomPos(0).y, 0.0));
TEST_ASSERT(feq(conf.getAtomPos(0).z, 0.0));
}
void testSDFGRoupMultiCoreNoneShouldMatch() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "testSDFGRoupMultiCoreNoneShouldMatch" << std::endl;
std::string sdcores = R"CTAB(
Mrv1813 05061918272D
13 14 0 0 0 0 999 V2000
-1.1505 0.0026 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.1505 -0.8225 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.4360 -1.2350 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
0.2784 -0.8225 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.2784 0.0026 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-0.4360 0.4151 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.9354 0.2575 0.0000 A 0 0 0 0 0 0 0 0 0 0 0 0
-2.4202 -0.4099 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.9354 -1.0775 0.0000 A 0 0 0 0 0 0 0 0 0 0 0 0
0.9907 -1.2333 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0
-0.4360 1.2373 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
0.2784 1.6497 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0
-3.2452 -0.4098 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0
6 1 1 0 0 0 0
1 7 1 0 0 0 0
1 2 1 0 0 0 0
2 3 1 0 0 0 0
9 2 1 0 0 0 0
3 4 1 0 0 0 0
4 5 1 0 0 0 0
4 10 1 0 0 0 0
5 6 1 0 0 0 0
6 11 1 0 0 0 0
7 8 1 0 0 0 0
8 13 1 0 0 0 0
8 9 1 0 0 0 0
11 12 1 0 0 0 0
M RGP 3 10 1 12 2 13 3
M END
$$$$
Mrv1813 05061918272D
13 14 0 0 0 0 999 V2000
6.9524 0.1684 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
6.9524 -0.6567 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
7.6668 -1.0692 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
8.3813 -0.6567 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
8.3813 0.1684 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
7.6668 0.5809 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
6.1674 0.4233 0.0000 A 0 0 0 0 0 0 0 0 0 0 0 0
5.6827 -0.2441 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
6.1674 -0.9117 0.0000 A 0 0 0 0 0 0 0 0 0 0 0 0
9.0935 -1.0675 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0
7.6668 1.4031 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
8.3813 1.8155 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0
4.8576 -0.2440 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0
6 1 1 0 0 0 0
1 7 1 0 0 0 0
1 2 1 0 0 0 0
2 3 1 0 0 0 0
9 2 1 0 0 0 0
3 4 1 0 0 0 0
4 5 1 0 0 0 0
4 10 1 0 0 0 0
5 6 1 0 0 0 0
6 11 1 0 0 0 0
7 8 1 0 0 0 0
8 13 1 0 0 0 0
8 9 1 0 0 0 0
11 12 1 0 0 0 0
M RGP 3 10 1 12 2 13 3
M END
$$$$)CTAB";
std::string sdmols = R"CTAB(
Mrv1813 05061918322D
15 17 0 0 0 0 999 V2000
0.1742 0.6899 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.8886 0.2774 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.8886 -0.5476 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.1742 -0.9601 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
0.1742 -1.7851 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.8886 -2.1976 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
0.8886 -3.0226 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.1742 -3.4351 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-0.5403 -3.0226 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.3249 -3.2775 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-1.8099 -2.6101 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.3249 -1.9426 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.5403 -2.1976 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.5403 -0.5476 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.5403 0.2774 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0 0 0 0
1 15 1 0 0 0 0
2 3 1 0 0 0 0
3 4 1 0 0 0 0
4 5 1 0 0 0 0
4 14 1 0 0 0 0
5 6 1 0 0 0 0
5 13 1 0 0 0 0
6 7 1 0 0 0 0
7 8 1 0 0 0 0
8 9 1 0 0 0 0
9 10 1 0 0 0 0
9 13 1 0 0 0 0
10 11 1 0 0 0 0
11 12 1 0 0 0 0
12 13 1 0 0 0 0
14 15 1 0 0 0 0
M END
$$$$
Mrv1813 05061918322D
14 15 0 0 0 0 999 V2000
6.4368 0.3002 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
5.7223 -0.1123 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
5.7223 -0.9373 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
6.4368 -1.3498 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
6.4368 -2.1748 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
5.7223 -2.5873 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
5.0078 -2.1748 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
4.2232 -2.4297 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0
3.7383 -1.7623 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
4.2232 -1.0949 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
3.9683 -0.3102 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
3.1613 -0.1387 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
4.5203 0.3029 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
5.0078 -1.3498 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0 0 0 0
2 3 1 0 0 0 0
3 4 1 0 0 0 0
3 14 1 0 0 0 0
4 5 1 0 0 0 0
5 6 1 0 0 0 0
6 7 1 0 0 0 0
7 8 1 0 0 0 0
7 14 1 0 0 0 0
8 9 1 0 0 0 0
9 10 1 0 0 0 0
10 11 1 0 0 0 0
10 14 1 0 0 0 0
11 13 1 0 0 0 0
11 12 1 0 0 0 0
M END
$$$$
Mrv1813 05061918322D
14 15 0 0 0 0 999 V2000
0.8289 -7.9643 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.1144 -8.3768 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
0.1144 -9.2018 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.8289 -9.6143 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
0.8289 -10.4393 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.1144 -10.8518 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.6000 -10.4393 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.3847 -10.6942 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0
-1.8696 -10.0268 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.3847 -9.3593 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.6396 -8.5747 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.4466 -8.4032 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.0876 -7.9616 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.6000 -9.6143 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0 0 0 0
2 3 1 0 0 0 0
3 4 1 0 0 0 0
3 14 1 0 0 0 0
4 5 1 0 0 0 0
5 6 1 0 0 0 0
6 7 1 0 0 0 0
7 8 1 0 0 0 0
7 14 1 0 0 0 0
8 9 1 0 0 0 0
9 10 1 0 0 0 0
10 11 1 0 0 0 0
10 14 1 0 0 0 0
11 13 1 0 0 0 0
11 12 1 0 0 0 0
M END
$$$$
Mrv1813 05061918322D
12 13 0 0 0 0 999 V2000
5.3295 -8.1871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
5.5844 -7.4025 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
5.0995 -6.7351 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
5.5844 -6.0676 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
6.3690 -6.3226 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
7.0835 -5.9101 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
7.0835 -5.0851 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
7.7980 -6.3226 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
7.7980 -7.1476 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
8.5124 -7.5601 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
7.0835 -7.5601 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
6.3690 -7.1476 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0 0 0 0
2 3 1 0 0 0 0
2 12 1 0 0 0 0
3 4 1 0 0 0 0
4 5 1 0 0 0 0
5 12 1 0 0 0 0
5 6 1 0 0 0 0
6 7 1 0 0 0 0
6 8 1 0 0 0 0
8 9 1 0 0 0 0
9 10 1 0 0 0 0
9 11 1 0 0 0 0
11 12 1 0 0 0 0
M END
$$$$)CTAB";
{
RGroupDecompositionParameters params;
params.onlyMatchAtRGroups = true;
params.removeHydrogensPostMatch = true;
std::vector<ROMOL_SPTR> cores;
{
SDMolSupplier sdsup;
sdsup.setData(sdcores);
while (!sdsup.atEnd()) {
cores.emplace_back(sdsup.next());
}
}
RGroupDecomposition decomp(cores, params);
{
SDMolSupplier sdsup;
sdsup.setData(sdmols);
while (!sdsup.atEnd()) {
ROMol *mol = sdsup.next();
TEST_ASSERT(mol);
int addedIndex = decomp.add(*mol);
TEST_ASSERT(addedIndex == -1); // none should match
delete mol;
}
}
}
{
RGroupDecompositionParameters params;
params.onlyMatchAtRGroups = false;
params.removeHydrogensPostMatch = true;
std::vector<ROMOL_SPTR> cores;
{
SDMolSupplier sdsup;
sdsup.setData(sdcores);
while (!sdsup.atEnd()) {
cores.emplace_back(sdsup.next());
}
}
RGroupDecomposition decomp(cores, params);
{
SDMolSupplier sdsup;
sdsup.setData(sdmols);
while (!sdsup.atEnd()) {
ROMol *mol = sdsup.next();
TEST_ASSERT(mol);
decomp.add(*mol);
delete mol;
}
}
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
/*
* Working on issue Github5613 these core smiles for the 3rd target no
* longer works, however the replacement is for the same core structure
*
const char *expected[4] = {
"Core:C1C([*:6])C2C(N([*:2])[*:4])NC([*:1])NC2N1[*:5] "
"R1:[H][*:1] R2:C(CC[*:2])CC[*:4] R4:C(CC[*:2])CC[*:4] R5:[H][*:5] "
"R6:[H][*:6]",
"Core:C1SC2NC([*:1])NC(N([*:2])[*:4])C2C1[*:6] "
"R1:[H][*:1] R2:C[*:2] R4:[H][*:4] R6:CC(C)[*:6]",
"Core:C1SC2CC([*:1])NC(N([*:2])[*:4])C2C1[*:6] "
"R1:[H][*:1] R2:C[*:2] R4:[H][*:4] R6:CC(C)[*:6]",
"Core:C1C2C(C(N([*:2])[*:4])NC1[*:1])N([*:6])CN2[*:5] R1:O[*:1] "
"R2:[H][*:2] R4:[H][*:4] R5:C[*:5] R6:[H][*:6]"};
*/
const char *expected[4] = {
"Core:C1C([*:6])C2C(N([*:2])[*:4])NC([*:1])NC2N1[*:5] "
"R1:[H][*:1] R2:C(CC[*:2])CC[*:4] R4:C(CC[*:2])CC[*:4] R5:[H][*:5] "
"R6:[H][*:6]",
"Core:C1SC2NC([*:1])NC(N([*:2])[*:4])C2C1[*:6] "
"R1:[H][*:1] R2:C[*:2] R4:[H][*:4] R6:CC(C)[*:6]",
"Core:C1C2SCC([*:6])C2C(N([*:2])[*:4])NC1[*:1] "
"R1:[H][*:1] R2:C[*:2] R4:[H][*:4] R6:CC(C)[*:6]",
"Core:C1C2C(C(N([*:2])[*:4])NC1[*:1])N([*:6])CN2[*:5] R1:O[*:1] "
"R2:[H][*:2] R4:[H][*:4] R5:C[*:5] R6:[H][*:6]"};
int i = 0;
for (RGroupRows::const_iterator it = rows.begin(); it != rows.end();
++it, ++i) {
TEST_ASSERT(i < 4);
// molzip doesn't support double attachment points yet
CHECK_RGROUP(it, expected[i]);
}
}
}
void testRowColumnAlignmentProblem() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "test a problem with row-column alignment"
<< std::endl;
std::vector<std::string> csmiles = {"c1c([*:1])cncn1", "c1c([*:1])cccn1"};
std::vector<ROMOL_SPTR> cores;
for (auto smi : csmiles) {
cores.emplace_back(SmilesToMol(smi));
}
std::vector<std::string> msmiles = {"c1c(F)cccn1", "c1c(F)cncn1",
"c1c(Cl)cccn1"};
std::vector<std::unique_ptr<RWMol>> mols;
for (auto smi : msmiles) {
mols.emplace_back(SmilesToMol(smi));
}
{
RGroupDecomposition decomp(cores);
for (const auto &mol : mols) {
TEST_ASSERT(decomp.add(*mol) >= 0);
}
decomp.process();
auto rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == mols.size());
// dump rgroups
const char *expected[] = {"Core:c1cncc([*:1])c1 R1:F[*:1]",
"Core:c1ncc([*:1])cn1 R1:F[*:1]",
"Core:c1cncc([*:1])c1 R1:Cl[*:1]"};
int i = 0;
for (RGroupRows::const_iterator it = rows.begin(); it != rows.end();
++it, ++i) {
CHECK_RGROUP(it, expected[i], mols[i].get());
}
for (const auto &row : rows) {
TEST_ASSERT(row.count("Core") == 1);
TEST_ASSERT(row.count("R1") == 1);
}
TEST_ASSERT(rows[0].count("R2") == 0);
TEST_ASSERT(rows[2].count("R2") == 0);
TEST_ASSERT(rows[1].count("R2") == 0);
auto cols = decomp.getRGroupsAsColumns();
auto &core = cols["Core"];
TEST_ASSERT(core.size() == 3);
auto &R1 = cols["R1"];
TEST_ASSERT(R1.size() == 3);
for (const auto &rg : R1) {
TEST_ASSERT(rg);
TEST_ASSERT(rg->getNumAtoms());
}
auto &R2 = cols["R2"];
TEST_ASSERT(R2.size() == 0);
}
}
void testSymmetryIssues() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "Testing R-Group symmetry issues\n";
auto m1 = "c1c(F)cccn1"_smiles;
auto m2 = "c1c(Cl)c(C)c(Br)cn1"_smiles;
auto m3 = "c1c(O)cccn1"_smiles;
auto m4 = "c1c(Br)c(C)c(F)cn1"_smiles;
auto core = "c1c([*:1])c([*:2])ccn1"_smiles;
{
RGroupDecomposition decomp(*core);
decomp.add(*m1);
decomp.add(*m2);
decomp.add(*m3);
decomp.add(*m4);
decomp.process();
std::stringstream ss;
auto groups = decomp.getRGroupsAsColumns();
std::set<std::string> r_labels;
for (auto &column : groups) {
r_labels.insert(column.first);
ss << "Rgroup===" << column.first << std::endl;
for (auto &rgroup : column.second) {
ss << MolToSmiles(*rgroup) << std::endl;
}
}
// We want three groups added, fluorine as R1 and bromine as R3
TEST_ASSERT(r_labels == std::set<std::string>({"Core", "R1", "R2", "R3"}));
TEST_ASSERT(groups.size() == 4);
TEST_ASSERT(ss.str() == R"RES(Rgroup===Core
c1ncc([*:3])c([*:2])c1[*:1]
c1ncc([*:3])c([*:2])c1[*:1]
c1ncc([*:3])c([*:2])c1[*:1]
c1ncc([*:3])c([*:2])c1[*:1]
Rgroup===R1
F[*:1]
Cl[*:1]
O[*:1]
F[*:1]
Rgroup===R2
[H][*:2]
C[*:2]
[H][*:2]
C[*:2]
Rgroup===R3
[H][*:3]
Br[*:3]
[H][*:3]
Br[*:3]
)RES");
}
{
// repeat that without symmetrization (testing #3224)
// Still three groups added, but bromine and fluorine
// are not aligned between R1 and R3
RGroupDecompositionParameters ps;
ps.matchingStrategy = RDKit::NoSymmetrization;
RGroupDecomposition decomp(*core, ps);
decomp.add(*m1);
decomp.add(*m2);
decomp.add(*m3);
decomp.add(*m4);
decomp.process();
std::stringstream ss;
auto groups = decomp.getRGroupsAsColumns();
std::set<std::string> r_labels;
for (auto &column : groups) {
r_labels.insert(column.first);
ss << "Rgroup===" << column.first << std::endl;
for (auto &rgroup : column.second) {
ss << MolToSmiles(*rgroup) << std::endl;
}
}
TEST_ASSERT(r_labels == std::set<std::string>({"Core", "R1", "R2", "R3"}));
TEST_ASSERT(groups.size() == 4);
TEST_ASSERT(ss.str() == R"RES(Rgroup===Core
c1ncc([*:3])c([*:2])c1[*:1]
c1ncc([*:3])c([*:2])c1[*:1]
c1ncc([*:3])c([*:2])c1[*:1]
c1ncc([*:3])c([*:2])c1[*:1]
Rgroup===R1
F[*:1]
Cl[*:1]
O[*:1]
Br[*:1]
Rgroup===R2
[H][*:2]
C[*:2]
[H][*:2]
C[*:2]
Rgroup===R3
[H][*:3]
Br[*:3]
[H][*:3]
F[*:3]
)RES");
}
}
void testSymmetryPerformance() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "Testing R-Group symmetry performance\n";
boost::logging::disable_logs("rdApp.warning");
std::string smis =
R"DATA(CN(C)Cc1cccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c1
CNc1cccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c1
Cc1cc2cc(Oc3cc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NC4CCN(C)CC4)c([N+](=O)[O-])c3)ccc2[nH]1
Cc1cc2cc(Oc3cc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCCCN4CCOCC4)c([N+](=O)[O-])c3)ccc2[nH]1
O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccccc1Cl
O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc(Cl)c1
O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccc(Cl)cc1
O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc([N+](=O)[O-])c1
O=C(NS(=O)(=O)c1ccc(NCCCN2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc(CO)c1
CN(C)CCCNc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)cc2Oc2ccccc2Cl)cc1[N+](=O)[O-]
O=C(NS(=O)(=O)c1ccc(NCCCN2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc(Cl)c1
O=C(NS(=O)(=O)c1ccc(NCCCN2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccc(Cl)cc1
CN(C)CCCNc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)cc2Oc2cccc(Cl)c2)cc1[N+](=O)[O-]
CN(C)CCCNc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)cc2Oc2ccc(Cl)cc2)cc1[N+](=O)[O-]
CN(C)CCCNc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)cc2Oc2cccc3c2ccn3C)cc1[N+](=O)[O-]
CC(=O)Nc1cccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c1
Nc1ccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)cc1
Nc1cccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c1
COc1cccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c1
CN(C)c1cccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c1
N#Cc1cccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c1
Cc1nc2ccc(Oc3cc(N4CCN(Cc5ccccc5-c5ccc(Cl)cc5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCC4CCOCC4)c([N+](=O)[O-])c3)cc2s1
Cc1nc2cc(Oc3cc(N4CCN(Cc5ccccc5-c5ccc(Cl)cc5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCCCN4CCOCC4)c([N+](=O)[O-])c3)ccc2s1
Cc1nc2cc(Oc3cc(N4CCN(Cc5ccccc5-c5ccc(Cl)cc5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCCCN(C)C)c([N+](=O)[O-])c3)ccc2s1
CN(C)C(=O)CCc1ccccc1Oc1cc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)ccc1C(=O)NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1
CN(C)C(=O)Cc1ccccc1Oc1cc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)ccc1C(=O)NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1
CN(C)CCCc1ccccc1Oc1cc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)ccc1C(=O)NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1
CN(C)CCc1ccccc1Oc1cc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)ccc1C(=O)NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1
CN(C)C(=O)c1ccccc1Oc1cc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)ccc1C(=O)NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1
CN(C)Cc1ccccc1Oc1cc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)ccc1C(=O)NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1
CN(C)CCCNc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)cc2Oc2cccc(N3CCOCC3)c2)cc1[N+](=O)[O-]
Cc1nc(C)c(-c2cccc(Oc3cc(N4CCN(Cc5ccccc5-c5ccc(Cl)cc5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCCCN4CCOCC4)c([N+](=O)[O-])c3)c2)s1
CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3cc(Cl)cc(Cl)c3)cc2[N+](=O)[O-])CC1
CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3cccc(Cl)c3)cc2[N+](=O)[O-])CC1
CN(C)CCOc1ccc(-c2ccc(Cl)cc2)c(CN2CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NC5CCN(C)CC5)c([N+](=O)[O-])c4)c(Oc4cccc(Cl)c4)c3)CC2)c1
CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)OC5)CC4)cc3Oc3ccccc3Cl)cc2[N+](=O)[O-])CC1
CN(C)CCOc1cccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c1
CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3ccc(N)c(Cl)c3)cc2[N+](=O)[O-])CC1
CC(C)N1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3ccccc3Cl)cc2[N+](=O)[O-])CC1
CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3ccccc3Br)cc2[N+](=O)[O-])CC1
CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CCCC5)CC4)cc3Oc3ccccc3Cl)cc2[N+](=O)[O-])CC1
Cc1n[nH]c2cccc(Oc3cc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCCCN4CCOCC4)c([N+](=O)[O-])c3)c12
CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3cccc(F)c3F)cc2[N+](=O)[O-])CC1
CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3cccc(Br)c3)cc2[N+](=O)[O-])CC1
CCN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3ccccc3Cl)cc2[N+](=O)[O-])CC1
CN1C(C)(C)CC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3ccccc3Cl)cc2[N+](=O)[O-])CC1(C)C
CC1(C)CCC(CN2CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NC5CCN(C6CCOCC6)CC5)c([N+](=O)[O-])c4)c(Oc4cccc(F)c4F)c3)CC2)=C(c2ccc(Cl)cc2)C1
CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3cc(F)c4[nH]ccc4c3)cc2[N+](=O)[O-])CC1
CC1(C)CCC(CN2CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NCCCN5CCOCC5)c([N+](=O)[O-])c4)c(Oc4cccc(F)c4F)c3)CC2)=C(c2ccc(Cl)cc2)C1
CC1(C)CCC(CN2CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NCCCN5CCOCC5)c([N+](=O)[O-])c4)c(Oc4ccc(N)c(Cl)c4)c3)CC2)=C(c2ccc(Cl)cc2)C1
O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3cc(CCN4CCCC4)ccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc(Cl)c1
CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3cccc(Cl)c3Cl)cc2[N+](=O)[O-])CC1
Cc1n[nH]c2cccc(Oc3cc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NC4CCN(C)CC4)c([N+](=O)[O-])c3)c12
CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CCCCC5)CC4)cc3Oc3ccccc3Cl)cc2[N+](=O)[O-])CC1
CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3cccc(C(F)(F)F)c3)cc2[N+](=O)[O-])CC1
CN(C)CCCNc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)cc2Oc2cccc3c2CCC(=O)N3)cc1[N+](=O)[O-]
CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3ccccc3Cl)cc2S(=O)(=O)C(F)(F)F)CC1
CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3cc(Cl)ccc3Cl)cc2[N+](=O)[O-])CC1
CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3ccc(F)cc3Cl)cc2[N+](=O)[O-])CC1
CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)C5)CC4)cc3Oc3ccccc3Cl)cc2[N+](=O)[O-])CC1
Cc1c[nH]c2cccc(Oc3cc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCCCN4CCOCC4)c([N+](=O)[O-])c3)c12
CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3cccc(C(F)(F)F)c3Cl)cc2[N+](=O)[O-])CC1
CC1(C)CCC(CN2CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NC5CCN(C6CC6)CC5)c([N+](=O)[O-])c4)c(Oc4ccccc4Cl)c3)CC2)=C(c2ccc(Cl)cc2)C1
Cc1c[nH]c2cccc(Oc3cc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NC4CCN(C)CC4)c([N+](=O)[O-])c3)c12
CC1(C)CCC(CN2CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NCCCN5CCOCC5)c([N+](=O)[O-])c4)c(Oc4cc(Cl)ccc4Cl)c3)CC2)=C(c2ccc(Cl)cc2)C1
Cn1ccc2c(Oc3cc(N4CCN(Cc5ccccc5-c5ccc(Cl)cc5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCCCN4CCOCC4)c([N+](=O)[O-])c3)cccc21
O=C(NS(=O)(=O)c1ccc(NCCCN2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc(N2CCOCC2)c1
CN(C)CCCNc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)cc2Oc2ccc3[nH]cc(CCC(=O)N4CCOCC4)c3c2)cc1[N+](=O)[O-]
O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc(OCc2ccccc2)c1
N#Cc1ccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)cc1
O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccc2[nH]cc(CCC(=O)N3CCOCC3)c2c1
O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccc2[nH]cc(CCCN3CCOCC3)c2c1
CN(C)Cc1ccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)cc1
O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccc(-n2ccnc2)cc1
O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)cc1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc([N+](=O)[O-])c1
CCN(Cc1ccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)cc1)C(=O)OC(C)(C)C
CCN(Cc1cccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c1)C(=O)OC(C)(C)C
CCNCc1ccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)cc1
CCNCc1cccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c1
CC(=O)Nc1ccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)cc1
CC(C)(C)OC(=O)Nc1ccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)cc1
O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccccc1-c1ccccc1
CC(C)(C)OC(=O)Nc1cccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c1
O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc(-c2ccccc2)c1
CN(C)CCc1ccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)cc1
O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccc(OCc2ccccc2)cc1
O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc(N2CCOCC2)c1
Cc1nc2cc(Oc3cc(N4CCN(Cc5ccccc5-c5ccc(Cl)cc5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCC4CCOCC4)c([N+](=O)[O-])c3)ccc2s1
CC(C)(C)OC(=O)N1CCN(c2cccc(Oc3cc(N4CCN(Cc5ccccc5-c5ccc(Cl)cc5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCC4CCOCC4)c([N+](=O)[O-])c3)c2)CC1
CN(C)CCCNc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)cc2Oc2cccc(OCc3ccccc3)c2)cc1[N+](=O)[O-]
O=C(NS(=O)(=O)c1ccc(NCCCN2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc(OCc2ccccc2)c1
O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccc(OCCN2CCOCC2)cc1
O=C1CCc2c(cccc2Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)N1
O=C(NS(=O)(=O)c1ccc(NCCCN2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccc(OCc2ccccc2)cc1
CC(C)(C)OC(=O)N1CCN(c2ccc(Oc3cc(N4CCN(Cc5ccccc5-c5ccc(Cl)cc5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCCCN4CCOCC4)c([N+](=O)[O-])c3)cc2)CC1
O=C(NS(=O)(=O)c1ccc(NCCCN2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc(-c2ccncc2)c1
O=C(NS(=O)(=O)c1ccc(NCCCN2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccc(-c2ccncc2)cc1
O=C(NS(=O)(=O)c1ccc(NCCCN2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccc(-c2cccnc2)cc1
CN(C)C(=O)COc1ccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)cc1
Cn1cnc2cc(Oc3cc(N4CCN(Cc5ccccc5-c5ccc(Cl)cc5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCCCN4CCOCC4)c([N+](=O)[O-])c3)ccc21)DATA";
std::vector<ROMOL_SPTR> ms;
boost::char_separator<char> sep(" \n");
tokenizer tokens(smis, sep);
for (tokenizer::iterator token = tokens.begin(); token != tokens.end();
++token) {
std::string smi = *token;
RWMol *m = SmilesToMol(smi);
TEST_ASSERT(m);
ms.push_back(ROMOL_SPTR(m));
}
auto core = "O=C(NS(=O)(=O)c1ccccc1)c1ccccc1Oc1ccccc1"_smiles;
{
std::cerr << "iterative" << std::endl;
RGroupDecompositionParameters ps = RGroupDecompositionParameters();
ps.timeout = 0.1;
RGroupDecomposition decomp(*core, ps);
bool ok = false;
int ndone = -1;
try {
for (auto m : ms) {
decomp.add(*m);
++ndone;
}
} catch (const std::runtime_error &) {
ok = true;
}
TEST_ASSERT(ok);
TEST_ASSERT(ndone >= 0);
}
{
RGroupDecompositionParameters ps = RGroupDecompositionParameters();
ps.timeout = 2.0;
std::cerr << "bulk" << std::endl;
std::vector<ROMOL_SPTR> cores;
cores.push_back(ROMOL_SPTR(new ROMol(*core)));
RGroupRows rows;
bool ok = false;
try {
auto res = RGroupDecompose(cores, ms, rows, nullptr, ps);
RDUNUSED_PARAM(res);
} catch (const std::runtime_error &) {
ok = true;
}
TEST_ASSERT(ok);
}
{
RGroupDecompositionParameters ps = RGroupDecompositionParameters();
#ifdef NDEBUG
ps.timeout = 5.0;
#else
ps.timeout = 25.0;
#endif
ps.matchingStrategy = RDKit::NoSymmetrization;
std::cerr << "bulk, no symmetry" << std::endl;
std::vector<ROMOL_SPTR> cores;
cores.push_back(ROMOL_SPTR(new ROMol(*core)));
RGroupRows rows;
bool ok = true;
try {
auto res = RGroupDecompose(cores, ms, rows, nullptr, ps);
RDUNUSED_PARAM(res);
} catch (const std::runtime_error &) {
ok = false;
}
TEST_ASSERT(ok);
}
boost::logging::enable_logs("rdApp.warning");
}
void testScorePermutations() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "Testing permutation scoring function\n";
{
auto core = "Cc1ccccc1"_smiles;
std::vector<RWMOL_SPTR> mols{"c1ccccc1C"_smiles, "Fc1ccccc1C"_smiles,
"c1cccc(F)c1C"_smiles, "Fc1cccc(F)c1C"_smiles};
RGroupDecomposition decomp(*core);
for (auto &m : mols) {
decomp.add(*m);
}
decomp.process();
std::stringstream ss;
auto groups = decomp.getRGroupsAsColumns();
std::set<std::string> r_labels;
for (auto &column : groups) {
r_labels.insert(column.first);
ss << "Rgroup===" << column.first << std::endl;
for (auto &rgroup : column.second) {
ss << MolToSmiles(*rgroup) << std::endl;
}
}
TEST_ASSERT(r_labels == std::set<std::string>({"Core", "R1", "R2"}));
TEST_ASSERT(groups.size() == 3);
std::string expected = R"RES(Rgroup===Core
Cc1c([*:1])cccc1[*:2]
Cc1c([*:1])cccc1[*:2]
Cc1c([*:1])cccc1[*:2]
Cc1c([*:1])cccc1[*:2]
Rgroup===R1
[H][*:1]
[H][*:1]
[H][*:1]
F[*:1]
Rgroup===R2
[H][*:2]
F[*:2]
F[*:2]
F[*:2]
)RES";
#ifdef DEBUG
if (ss.str() != expected) {
std::cerr << __LINE__ << " ERROR got\n"
<< ss.str() << "\nexpected\n"
<< expected << std::endl;
}
#else
TEST_ASSERT(ss.str() == expected);
#endif
}
{
auto core = "Cc1ccccc1"_smiles;
std::vector<RWMOL_SPTR> mols{
"c1(Cl)cccc(Cl)c1C"_smiles, "Fc1cccc(Cl)c1C"_smiles,
"Clc1cccc(F)c1C"_smiles, "Fc1cccc(F)c1C"_smiles};
RGroupDecomposition decomp(*core);
for (auto &m : mols) {
decomp.add(*m);
}
decomp.process();
std::stringstream ss;
auto groups = decomp.getRGroupsAsColumns();
std::set<std::string> r_labels;
for (auto &column : groups) {
r_labels.insert(column.first);
ss << "Rgroup===" << column.first << std::endl;
for (auto &rgroup : column.second) {
ss << MolToSmiles(*rgroup) << std::endl;
}
}
TEST_ASSERT(r_labels == std::set<std::string>({"Core", "R1", "R2"}));
TEST_ASSERT(groups.size() == 3);
std::string expected = R"RES(Rgroup===Core
Cc1c([*:1])cccc1[*:2]
Cc1c([*:1])cccc1[*:2]
Cc1c([*:1])cccc1[*:2]
Cc1c([*:1])cccc1[*:2]
Rgroup===R1
Cl[*:1]
Cl[*:1]
Cl[*:1]
F[*:1]
Rgroup===R2
Cl[*:2]
F[*:2]
F[*:2]
F[*:2]
)RES";
#ifdef DEBUG
if (ss.str() != expected) {
std::cerr << __LINE__ << " ERROR got\n"
<< ss.str() << "\nexpected\n"
<< expected << std::endl;
}
#else
TEST_ASSERT(ss.str() == expected);
#endif
}
{
auto core = "O1C([*:1])([*:2])CCC1"_smiles;
std::vector<RWMOL_SPTR> mols{"NC1CCCO1"_smiles,
"OC1CCCO1"_smiles,
"SC1CCCO1"_smiles,
"O1C2(CN2)CCC1"_smiles,
"OC1(P)CCCO1"_smiles,
"NC1(O)CCCO1"_smiles,
"CC1(N)CCCO1"_smiles,
"CCC1(C)CCCO1"_smiles,
"CCC1(C(C)C)CCCO1"_smiles,
"CCC1(Cc2ccccc2)CCCO1"_smiles,
"OCC1(Cc2ccccc2)CCCO1"_smiles,
"CCCC1(CO)CCCO1"_smiles,
"CCCCC1(CC(C)C)CCCO1"_smiles};
RGroupDecompositionParameters params;
params.removeHydrogensPostMatch = true;
params.onlyMatchAtRGroups = true;
RGroupDecomposition decomp(*core, params);
for (auto &m : mols) {
auto res = decomp.add(*m);
TEST_ASSERT(res != -1);
}
decomp.process();
std::stringstream ss;
auto groups = decomp.getRGroupsAsColumns();
std::set<std::string> r_labels;
for (auto &column : groups) {
r_labels.insert(column.first);
ss << "Rgroup===" << column.first << std::endl;
for (auto &rgroup : column.second) {
ss << MolToSmiles(*rgroup) << std::endl;
}
}
TEST_ASSERT(r_labels == std::set<std::string>({"Core", "R1", "R2"}));
TEST_ASSERT(groups.size() == 3);
std::string expected = R"RES(Rgroup===Core
C1COC([*:1])([*:2])C1
C1COC([*:1])([*:2])C1
C1COC([*:1])([*:2])C1
C1COC([*:1])([*:2])C1
C1COC([*:1])([*:2])C1
C1COC([*:1])([*:2])C1
C1COC([*:1])([*:2])C1
C1COC([*:1])([*:2])C1
C1COC([*:1])([*:2])C1
C1COC([*:1])([*:2])C1
C1COC([*:1])([*:2])C1
C1COC([*:1])([*:2])C1
C1COC([*:1])([*:2])C1
Rgroup===R1
N[*:1]
O[*:1]
S[*:1]
C(N[*:1])[*:2]
P[*:1]
O[*:1]
N[*:1]
C[*:1]
CC(C)[*:1]
c1ccc(C[*:1])cc1
c1ccc(C[*:1])cc1
OC[*:1]
CC(C)C[*:1]
Rgroup===R2
[H][*:2]
[H][*:2]
[H][*:2]
C(N[*:1])[*:2]
O[*:2]
N[*:2]
C[*:2]
CC[*:2]
CC[*:2]
CC[*:2]
OC[*:2]
CCC[*:2]
CCCC[*:2]
)RES";
if (ss.str() != expected) {
std::cerr << __LINE__ << " ERROR got\n"
<< ss.str() << "\nexpected\n"
<< expected << std::endl;
}
TEST_ASSERT(ss.str() == expected);
}
}
void testMultiCorePreLabelled() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "test multi core pre-labelled" << std::endl;
struct MultiCoreRGD {
static void test(
const std::vector<ROMOL_SPTR> &cores,
RGroupDecompositionParameters &params,
const std::vector<std::string> &expectedLabels,
const std::vector<std::string> &expectedRows,
const std::vector<std::vector<std::string>> &expectedItems) {
std::vector<ROMOL_SPTR> mols{"CNC(=O)C1=CN=CN1CC"_smiles,
"Fc1ccc2ccc(Br)nc2n1"_smiles};
params.removeHydrogensPostMatch = true;
params.onlyMatchAtRGroups = true;
RGroupDecomposition decomp(cores, params);
unsigned int i = 0;
for (const auto &m : mols) {
unsigned int res = decomp.add(*m);
TEST_ASSERT(res == i++);
}
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
i = 0;
for (RGroupRows::const_iterator it = rows.begin(); it != rows.end();
++it, ++i) {
CHECK_RGROUP(it, expectedRows[i]);
}
RGroupColumns groups = decomp.getRGroupsAsColumns();
i = 0;
TEST_ASSERT(groups.size() <= expectedLabels.size());
for (const auto &pair : groups) {
#ifdef DEBUG
if (pair.first != expectedLabels[i]) {
std::cerr << __LINE__ << " ERROR: Expected " << expectedLabels[i]
<< ", got " << pair.first << std::endl;
}
#else
TEST_ASSERT(pair.first == expectedLabels[i]);
#endif
unsigned int j = 0;
for (const auto &item : pair.second) {
#ifdef DEBUG
if (expectedItems[i][j] != MolToSmiles(*item)) {
std::cerr << __LINE__ << " ERROR: Expected " << expectedItems[i][j]
<< ", got " << MolToSmiles(*item) << std::endl;
}
#else
TEST_ASSERT(expectedItems[i][j] == MolToSmiles(*item));
#endif
++j;
}
++i;
}
}
};
std::string sdcores = R"CTAB(
RDKit 2D
9 9 0 0 0 0 0 0 0 0999 V2000
1.1100 -1.3431 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
1.5225 -0.6286 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.9705 -0.0156 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.2168 -0.3511 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
0.3029 -1.1716 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1.1419 0.7914 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.5289 1.3431 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
1.9266 1.0463 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0
-0.4976 0.0613 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0
2 3 2 0
3 4 1 0
4 5 1 0
1 5 2 0
3 6 1 0
6 7 2 0
6 8 1 0
4 9 1 0
M RGP 2 8 1 9 2
V 8 *
V 9 *
M END
$$$$
RDKit 2D
12 13 0 0 0 0 0 0 0 0999 V2000
-6.5623 0.3977 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0
-5.8478 -0.0147 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-5.1333 0.3977 0.0000 A 0 0 0 0 0 0 0 0 0 0 0 0
-4.4188 -0.0147 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-4.4188 -0.8397 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-5.1333 -1.2522 0.0000 A 0 0 0 0 0 0 0 0 0 0 0 0
-5.8478 -0.8397 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.7044 -1.2522 0.0000 A 0 0 0 0 0 0 0 0 0 0 0 0
-3.7044 0.3977 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-2.9899 -0.0147 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.9899 -0.8397 0.0000 A 0 0 0 0 0 0 0 0 0 0 0 0
-2.2754 0.3978 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0
3 4 1 0
4 5 2 0
5 6 1 0
6 7 2 0
2 3 2 0
2 7 1 0
9 10 2 0
10 11 1 0
8 11 2 0
8 5 1 0
4 9 1 0
10 12 1 0
1 2 1 0
M RGP 2 1 2 12 1
V 1 *
V 12 *
M END
$$$$
)CTAB";
std::vector<ROMOL_SPTR> cores;
SDMolSupplier sdsup;
sdsup.setData(sdcores);
while (!sdsup.atEnd()) {
cores.emplace_back(sdsup.next());
}
std::vector<std::string> expectedRows{
"Core:O=C(c1cncn1[*:2])[*:1] R1:CN[*:1] R2:CC[*:2]",
"Core:c1cc2ccc([*:2])nc2nc1[*:1] R1:F[*:1] R2:Br[*:2]"};
std::vector<std::vector<std::string>> expectedItems{
{"O=C(c1cncn1[*:2])[*:1]", "c1cc2ccc([*:2])nc2nc1[*:1]"},
{"CN[*:1]", "F[*:1]"},
{"CC[*:2]", "Br[*:2]"},
};
std::vector<std::string> expectedLabels{"Core", "R1", "R2"};
RGroupDecompositionParameters params;
// test pre-labelled with MDL R-group labels, autodetect
params.labels = AutoDetect;
params.alignment = MCS;
MultiCoreRGD::test(cores, params, expectedLabels, expectedRows,
expectedItems);
// test pre-labelled with MDL R-group labels, no autodetect
params.labels = MDLRGroupLabels | RelabelDuplicateLabels;
params.alignment = MCS;
MultiCoreRGD::test(cores, params, expectedLabels, expectedRows,
expectedItems);
// test pre-labelled with MDL R-group labels, autodetect, no MCS alignment
params.labels = AutoDetect;
params.alignment = NoAlignment;
MultiCoreRGD::test(cores, params, expectedLabels, expectedRows,
expectedItems);
// Reading from a MDL molblock also sets isotopic labels, so no need
// to set them again; we only clear MDL R-group labels
for (auto &core : cores) {
for (auto a : core->atoms()) {
if (a->hasProp(common_properties::_MolFileRLabel)) {
a->clearProp(common_properties::_MolFileRLabel);
}
}
}
// test pre-labelled with isotopic labels, autodetect
params.labels = AutoDetect;
params.alignment = MCS;
MultiCoreRGD::test(cores, params, expectedLabels, expectedRows,
expectedItems);
// test pre-labelled with isotopic labels, no autodetect
params.labels = IsotopeLabels | RelabelDuplicateLabels;
params.alignment = MCS;
MultiCoreRGD::test(cores, params, expectedLabels, expectedRows,
expectedItems);
// test pre-labelled with isotopic labels, autodetect, no MCS alignment
params.labels = AutoDetect;
params.alignment = NoAlignment;
MultiCoreRGD::test(cores, params, expectedLabels, expectedRows,
expectedItems);
for (auto &core : cores) {
for (auto a : core->atoms()) {
auto iso = a->getIsotope();
if (iso) {
a->setAtomMapNum(iso);
a->setIsotope(0);
}
}
}
// test pre-labelled with atom map labels, autodetect
params.labels = AutoDetect;
params.alignment = MCS;
MultiCoreRGD::test(cores, params, expectedLabels, expectedRows,
expectedItems);
// test pre-labelled with atom map labels, no autodetect
params.labels = AtomMapLabels | RelabelDuplicateLabels;
params.alignment = MCS;
MultiCoreRGD::test(cores, params, expectedLabels, expectedRows,
expectedItems);
// test pre-labelled with atom map labels, autodetect, no MCS alignment
params.labels = AutoDetect;
params.alignment = NoAlignment;
MultiCoreRGD::test(cores, params, expectedLabels, expectedRows,
expectedItems);
for (auto &core : cores) {
for (auto a : core->atoms()) {
if (a->getAtomMapNum()) {
a->setAtomMapNum(0);
}
}
}
// test pre-labelled with dummy atom labels, autodetect
expectedRows = {"Core:O=C(c1cncn1[*:2])[*:1] R1:CN[*:1] R2:CC[*:2]",
"Core:c1cc2ccc([*:2])nc2nc1[*:1] R1:Br[*:1] R2:F[*:2]"};
expectedItems = {{"O=C(c1cncn1[*:2])[*:1]", "c1cc2ccc([*:2])nc2nc1[*:1]"},
{"CN[*:1]", "Br[*:1]"},
{"CC[*:2]", "F[*:2]"}};
params.labels = AutoDetect;
params.alignment = MCS;
MultiCoreRGD::test(cores, params, expectedLabels, expectedRows,
expectedItems);
MultiCoreRGD::test(cores, params, expectedLabels, expectedRows,
expectedItems);
// test pre-labelled with dummy atom labels, no autodetect
params.labels = DummyAtomLabels | RelabelDuplicateLabels;
params.alignment = MCS;
MultiCoreRGD::test(cores, params, expectedLabels, expectedRows,
expectedItems);
}
void testCoreWithRGroupAdjQuery() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "test core with query atom adjacent to R-group"
<< std::endl;
std::string sdcore_query = R"CTAB(
RDKit 2D
10 10 0 0 0 0 0 0 0 0999 V2000
-3.6689 -0.8582 0.0000 R# 0 0 0 0 0 1 0 0 0 0 0 0
-2.2421 -1.3211 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-1.1279 -0.3169 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.4403 1.1502 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.3261 2.1543 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1.1007 1.6914 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1.4132 0.2243 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.2989 -0.7798 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
2.8400 -0.2386 0.0000 Q 0 0 0 0 0 0 0 0 0 0 0 0
3.1525 -1.7057 0.0000 R# 0 0 0 0 0 1 0 0 0 0 0 0
1 2 1 0
2 3 1 0
3 4 2 0
4 5 1 0
5 6 2 0
6 7 1 0
7 8 2 0
7 9 1 0
9 10 1 0
8 3 1 0
M RGP 2 1 1 10 2
M END
$$$$
)CTAB";
std::string sdcore_noquery =
std::regex_replace(sdcore_query, std::regex("Q "), "O ");
auto mol = "CNc1cccc(c1)OC1CCC1"_smiles;
for (const auto &sdcore : {sdcore_query, sdcore_noquery}) {
SDMolSupplier sdsup;
sdsup.setData(sdcore);
ROMOL_SPTR core(sdsup.next());
RGroupDecompositionParameters params;
params.removeHydrogensPostMatch = true;
params.onlyMatchAtRGroups = true;
RGroupDecomposition decomp(*core, params);
TEST_ASSERT(decomp.add(*mol) == 0);
TEST_ASSERT(decomp.process());
RGroupColumns groups = decomp.getRGroupsAsColumns();
TEST_ASSERT(groups.size() == 3);
TEST_ASSERT(groups.find("R1") != groups.end());
TEST_ASSERT(groups.find("R2") != groups.end());
TEST_ASSERT(MolToSmiles(*groups.at("R1")[0]) == "C[*:1]");
TEST_ASSERT(MolToSmiles(*groups.at("R2")[0]) == "C1CC([*:2])C1");
auto rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1)
RGroupRows::const_iterator it = rows.begin();
std::string expected(
"Core:c1cc(N[*:1])cc(O[*:2])c1 R1:C[*:1] R2:C1CC([*:2])C1");
CHECK_RGROUP(it, expected);
}
}
void testMultipleCoreRelabellingIssues() {
// This test fixes 2 issues with relabelling groups
// Firstly, a new R group which appeared in a later core could have it's label
// assigned to an unindexed group in a previous core
// Secondly, a user defined r group which is not part of the decomposition
// could have it's index assigned to an unindexed group.
// See https://github.com/rdkit/rdkit/pull/3565
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "Test relabelling issues in multiple core decomp"
<< std::endl;
std::vector<std::shared_ptr<ROMol>> molecules;
{
std::fstream fh;
std::string rdBase(getenv("RDBASE"));
fh.open(rdBase + "/Docs/Notebooks/compounds.txt", std::ios::in);
std::string line;
getline(fh, line);
while (getline(fh, line)) {
int pos = line.find_last_of("\t");
auto smiles = line.substr(pos + 1);
std::shared_ptr<ROMol> mol(SmilesToMol(smiles));
molecules.push_back(mol);
if (molecules.size() == 30) {
break;
}
}
}
std::vector<std::string> smi{
"O=C1C([*:2])([*:1])[C@@H]2N1C(C(O)=O)C([*:3])([*:4])S2",
"O=C1C([*:2])([*:1])[C@@H]2N1C(C(O)=O)=C([*:3])CS2",
"O=C1C([*:2])([*:1])[C@@H]2N1C(C(O)=O)=C([*:3])CC2",
"O=C1C([*:2])([*:1])[C@@H]2N1C(C(O)=O)=C([*:3])CO2",
"O=C1C([*:2])([*:1])[C@@H]2N1C(C(O)=O)=C([*:3])C2",
"O=C1C([*:2])([*:1])[C@@H]2N1C(C(O)=O)C([*:3])([*:4])C2",
"O=C1C([*:2])([*:1])[C@@H]2N1C(C(O)=O)=C([*:3])S2",
"O=C1C([*:2])([*:1])[C@@H]2N1C(C(O)=O)C([*:3])([*:4])S2",
"O=C1C([*:2])([*:1])[C@@H]2N1C(C(O)=O)C([*:3])([*:4])O2",
"O=C1C([*:2])([*:1])C([*:6])([*:5])N1"};
std::vector<RGroupScore> matchtypes{Match, FingerprintVariance};
for (auto match : matchtypes) {
std::vector<ROMOL_SPTR> cores;
for (const auto &s : smi) {
cores.emplace_back(SmartsToMol(s));
}
RGroupDecompositionParameters params;
params.scoreMethod = match;
RGroupDecomposition decomposition(cores, params);
for (auto &mol : molecules) {
decomposition.add(*mol);
}
decomposition.process();
const auto &columns = decomposition.getRGroupsAsColumns();
TEST_ASSERT(columns.size() == 7u);
for (auto &col : columns) {
TEST_ASSERT(30U == col.second.size());
}
}
}
void testUnprocessedMapping() {
// Tests a bug that results in an unprocessed mapping Invariant violation
// The cause of the error is an rgroup mistakenly identified as containing
// only hydrogens in a multicore decomp
// See https://github.com/rdkit/rdkit/pull/3565
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog)
<< "Test unprocessed mapping error in multiple core decomp" << std::endl;
std::vector<std::string> structureSmi = {
"Cn1nc(-c2ccccc2)cc1OC1CCC(OC2CCN(C(=O)OC(C)(C)C)CC2)CC1",
"Cc1cccc(N2CCN(c3ncnc(Nc4ccc(S(C)(=O)=O)nc4C)c3F)[C@@H](C)C2)c1",
"CC(C)(C)OC(=O)N1CCC(OCC2CCCCC2COc2ccc(Br)nn2)CC1",
"CC(C)(C)OC(=O)N1CCC(CO[C@H]2CC[C@@H](c3ccc(S(C)(=O)=O)nc3)CC2)CC1",
"CCCCCCCC/"
"C=C\\CCCCCCCC(=O)Oc1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12"};
std::vector<std::string> coreSmi = {"N1([*:1])CCN([*:2])CC1",
"C1(O[*:1])CCC(O[*:2])CC1",
"C1([*:1])CCC([*:2])CC1"};
std::vector<RGroupScore> matchtypes{Match, FingerprintVariance};
for (auto match : matchtypes) {
std::vector<ROMOL_SPTR> cores;
for (const auto &s : coreSmi) {
cores.emplace_back(SmartsToMol(s));
}
RGroupDecompositionParameters params;
params.scoreMethod = match;
RGroupDecomposition decomposition(cores, params);
for (auto &smi : structureSmi) {
auto mol = SmilesToMol(smi);
decomposition.add(*mol);
delete mol;
}
auto result = decomposition.processAndScore();
TEST_ASSERT(result.success);
TEST_ASSERT(result.score != -1.0);
}
}
void testGeminalRGroups() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "test core with geminal R-groups" << std::endl;
std::string core_ctab = R"CTAB(
RDKit 2D
8 8 0 0 0 0 0 0 0 0999 V2000
-0.6026 1.2267 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.3171 0.8142 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.3171 -0.0108 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.6026 -0.4232 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.1118 -0.0108 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.1118 0.8142 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.0714 1.7839 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0
-0.0506 1.8398 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0
2 3 1 0 0 0 0
3 4 1 0 0 0 0
4 5 1 0 0 0 0
5 6 1 0 0 0 0
1 2 1 0 0 0 0
1 6 1 0 0 0 0
1 7 1 0 0 0 0
1 8 1 0 0 0 0
M RGP 2 7 5 8 6
M END
)CTAB";
ROMOL_SPTR core(MolBlockToMol(core_ctab));
const std::vector<const char *> smilesData{"C1CCCCC12CC2", "C1CCCCC1(C)C",
"C1CCCCC1(Cl)Br"};
// the test should yield the same results irrespective of the permutations
// across the two parameters
for (auto matchAtRGroup = 0; matchAtRGroup < 2; ++matchAtRGroup) {
for (auto mdlRGroupLabels = 0; mdlRGroupLabels < 2; ++mdlRGroupLabels) {
RGroupDecompositionParameters params;
if (matchAtRGroup) {
params.labels = MDLRGroupLabels;
}
if (mdlRGroupLabels) {
params.labels = MDLRGroupLabels;
}
RGroupDecomposition decomp(*core, params);
for (const auto &smi : smilesData) {
ROMol *mol = SmilesToMol(smi);
TEST_ASSERT(decomp.add(*mol) != -1);
delete mol;
}
TEST_ASSERT(decomp.process());
auto rows = decomp.getRGroupsAsRows();
const std::vector<const char *> res{
"Core:C1CCC([*:5])([*:6])CC1 R5:C(C[*:6])[*:5] R6:C(C[*:6])[*:5]",
"Core:C1CCC([*:5])([*:6])CC1 R5:C[*:5] R6:C[*:6]",
"Core:C1CCC([*:5])([*:6])CC1 R5:Br[*:5] R6:Cl[*:6]"};
TEST_ASSERT(rows.size() == res.size());
size_t i = 0;
for (RGroupRows::const_iterator it = rows.begin(); it != rows.end();
++it) {
CHECK_RGROUP(it, res.at(i++));
}
}
}
}
void testMatchOnAnyAtom() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "Test core with matching at any atom" << std::endl;
std::string core_ctab = R"CTAB(
Mrv2008 01192109352D
12 12 0 0 0 0 999 V2000
3.7389 -3.2028 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
4.5640 -3.2028 0.0000 A 0 0 0 0 0 0 0 0 0 0 0 0
4.9764 -2.4884 0.0000 A 0 0 0 0 0 0 0 0 0 0 0 0
4.5640 -1.7739 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
3.7389 -1.7739 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
3.3265 -2.4884 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
2.5015 -2.4884 0.0000 A 0 0 0 0 0 0 0 0 0 0 0 0
3.3265 -3.9172 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0
5.8014 -2.4884 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0
2.0890 -1.7739 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
2.5015 -1.0595 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
1.2640 -1.7739 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0
5 6 8 0 0 0 0
4 5 8 0 0 0 0
3 4 8 0 0 0 0
2 3 8 0 0 0 0
1 2 8 0 0 0 0
1 6 8 0 0 0 0
6 7 1 0 0 0 0
1 8 1 0 0 0 0
3 9 1 0 0 0 0
7 10 1 0 0 0 0
10 11 2 0 0 0 0
10 12 1 0 0 0 0
M RGP 3 8 2 9 3 12 1
M END
)CTAB";
ROMOL_SPTR core(MolBlockToMol(core_ctab));
const std::vector<const char *> smilesData{""};
RGroupDecompositionParameters params;
params.onlyMatchAtRGroups = false;
RGroupDecomposition decomp(*core, params);
auto mol = "O=C(NC1CCN(c2ncccc2[N+](=O)[O-])CC1)c1cc(Cl)c(Cl)[nH]1"_smiles;
int res = decomp.add(*mol);
TEST_ASSERT(res == 0);
decomp.process();
auto rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1)
RGroupRows::const_iterator it = rows.begin();
std::string expected(
"Core:O=C(NC1CCN([*:3])CC1)[*:1] R1:Clc1cc([*:1])[nH]c1Cl "
"R3:O=[N+]([O-])c1cccnc1[*:3]");
CHECK_RGROUP(it, expected);
params.onlyMatchAtRGroups = true;
RGroupDecomposition decomp2(*core, params);
res = decomp2.add(*mol);
TEST_ASSERT(res == 0);
decomp2.process();
rows = decomp2.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1)
it = rows.begin();
CHECK_RGROUP(it, expected);
}
void testNoAlignmentAndSymmetry() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "test NoAlignment with symmetric groups" << std::endl;
const std::vector<ROMOL_SPTR> cores{"c([*:1])1c([*:2])c([*:3])ccc1"_smiles,
"c([*:3])1c([*:2])c([*:1])cnc1"_smiles};
const std::vector<const char *> smilesData{"c1(CO)c(F)c(CN)ccc1",
"c1(CO)c(Cl)c(CN)cnc1"};
RGroupDecompositionParameters params;
params.onlyMatchAtRGroups = true;
params.removeHydrogensPostMatch = true;
params.alignment = NoAlignment;
RGroupDecomposition decomp(cores, params);
size_t i = 0;
for (const auto &smi : smilesData) {
ROMOL_SPTR mol(static_cast<ROMol *>(SmilesToMol(smi)));
TEST_ASSERT(decomp.add(*mol) == static_cast<int>(i++));
}
TEST_ASSERT(decomp.process());
auto rows = decomp.getRGroupsAsRows();
const std::vector<const char *> res{
"Core:c1cc([*:1])c([*:2])c([*:3])c1 R1:NC[*:1] R2:F[*:2] R3:OC[*:3]",
"Core:c1ncc([*:3])c([*:2])c1[*:1] R1:NC[*:1] R2:Cl[*:2] R3:OC[*:3]"};
TEST_ASSERT(rows.size() == res.size());
i = 0;
for (RGroupRows::const_iterator it = rows.begin(); it != rows.end(); ++it) {
CHECK_RGROUP(it, res.at(i++));
}
}
void testSingleAtomBridge() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "test single atom bridge between 2 user r groups"
<< std::endl;
auto core = "C1([*:1])C([*:2])CC1"_smiles;
RGroupDecompositionParameters params;
RGroupDecomposition decomp(*core, params);
auto mol = "C1CC2NC12"_smiles;
params.onlyMatchAtRGroups = true;
auto res = decomp.add(*mol);
TEST_ASSERT(res == 0);
TEST_ASSERT(decomp.process());
auto rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1)
const std::string expected(
"Core:C1CC([*:2])C1[*:1] R1:N([*:1])[*:2]"
" R2:N([*:1])[*:2]");
RGroupRows::const_iterator it = rows.begin();
CHECK_RGROUP(it, expected);
core = "C1([*:1])CCC1"_smiles;
RGroupDecomposition decomp3(*core, params);
res = decomp3.add(*mol);
TEST_ASSERT(res == -1);
params.onlyMatchAtRGroups = false;
RGroupDecomposition decomp2(*core, params);
res = decomp2.add(*mol);
TEST_ASSERT(res == 0);
TEST_ASSERT(decomp2.process());
rows = decomp2.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1)
it = rows.begin();
CHECK_RGROUP(it, expected);
params.onlyMatchAtRGroups = true;
params.allowNonTerminalRGroups = true;
core = "C1([*:1])[*:2]CC1"_smiles;
RGroupDecomposition decomp4(*core, params);
res = decomp4.add(*mol);
TEST_ASSERT(res == 0);
TEST_ASSERT(rows.size() == 1)
it = rows.begin();
CHECK_RGROUP(it, expected);
// Now that issue 4505 (Cores with query atoms may fail to R-group-decompose
// molecules) is resolved this will match with no substitution for R3
core = "C1([*:1])C([*:2])*([*:3])C1"_smiles;
params.onlyMatchAtRGroups = true;
RGroupDecomposition decomp5(*core, params);
mol = "C1OC2NC12"_smiles;
res = decomp5.add(*mol);
TEST_ASSERT(res == 0);
TEST_ASSERT(rows.size() == 1)
it = rows.begin();
CHECK_RGROUP(it, expected);
}
void testAddedRGroupsHaveCoords() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "test added R groups have non-zero coords"
<< std::endl;
auto core = R"CTAB(
RDKit 2D
13 14 0 0 0 0 0 0 0 0999 V2000
-3.9955 2.1866 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-4.7099 1.7741 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-4.7099 0.9490 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.9955 0.5365 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.2810 0.9490 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.2810 1.7741 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-5.4244 2.1866 0.0000 R1 0 0 0 0 0 0 0 0 0 0 0 0
-3.9956 -0.2884 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.2811 -0.7009 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.1948 -1.5214 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.3878 -1.6929 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.9753 -0.9785 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-2.5274 -0.3654 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1 2 2 0 0 0 0
2 3 1 0 0 0 0
3 4 2 0 0 0 0
4 5 1 0 0 0 0
5 6 2 0 0 0 0
6 1 1 0 0 0 0
4 8 1 0 0 0 0
8 9 1 0 0 0 0
10 11 1 0 0 0 0
9 10 1 0 0 0 0
9 13 1 0 0 0 0
11 12 1 0 0 0 0
12 13 1 0 0 0 0
2 7 1 0 0 0 0
M RGP 1 7 1
M END
)CTAB"_ctab;
TEST_ASSERT(core);
auto mol = "COc1ccc(CC2CCNC2)cc1NC(C)=O"_smiles;
RGroupDecompositionParameters params;
RGroupDecomposition decomp(*core, params);
TEST_ASSERT(decomp.add(*mol) == 0);
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
for (const auto &row : rows) {
auto it = row.find("Core");
TEST_ASSERT(it != row.end());
const auto &rgdCore = it->second;
TEST_ASSERT(rgdCore->getNumConformers() == 1);
size_t r2Num = 0;
for (const auto atom : rgdCore->atoms()) {
// test that R2 has non-zero coords and a sensible bond length
// to its neighboring atom
if (atom->getAtomicNum() == 0 && atom->getAtomMapNum() == 2) {
++r2Num;
auto &r2Coord = rgdCore->getConformer().getAtomPos(atom->getIdx());
TEST_ASSERT(fabs(r2Coord.x) > 1e-4);
TEST_ASSERT(fabs(r2Coord.y) > 1e-4);
for (const auto &nbri :
boost::make_iterator_range(rgdCore->getAtomNeighbors(atom))) {
const auto nbr = (*rgdCore)[nbri];
const auto bond =
rgdCore->getBondBetweenAtoms(nbr->getIdx(), atom->getIdx());
TEST_ASSERT(bond);
auto &nbrCoord = rgdCore->getConformer().getAtomPos(nbr->getIdx());
auto bondLen = (nbrCoord - r2Coord).length();
TEST_ASSERT(fabs(bondLen - 1.0) < 0.1);
}
TEST_ASSERT(atom->getDegree() == 1);
}
}
TEST_ASSERT(r2Num == 1);
}
}
void testUserMatchTypes() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "Test user rgroup label specification and matching"
<< std::endl;
struct TestMatchType {
static void test(RWMol &core, RWMol &mol,
RGroupDecompositionParameters &parameters,
std::string &expected) {
RGroupDecomposition decomp(core, parameters);
auto res = decomp.add(mol);
TEST_ASSERT(res == 0);
TEST_ASSERT(decomp.process());
auto rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1)
RGroupRows::const_iterator it = rows.begin();
CHECK_RGROUP(it, expected);
}
};
std::vector<RGroupScore> matchtype{Match, FingerprintVariance};
for (auto match : matchtype) {
auto mol = "C1CCCCC1(N)(O)"_smiles;
auto core = "C1CCCCC1[*:1]"_smiles;
core = "C1CCCCC1[*:1]"_smarts;
RGroupDecompositionParameters params;
params.onlyMatchAtRGroups = true;
params.scoreMethod = match;
RGroupDecomposition decomp(*core, params);
int res = decomp.add(*mol);
TEST_ASSERT(res == -1);
params.onlyMatchAtRGroups = false;
std::string expected("Core:C1CCC([*:1])([*:2])CC1 R1:O[*:1] R2:N[*:2]");
TestMatchType::test(*core, *mol, params, expected);
core = "C1CCCCC1([*:1])([*:2])"_smiles;
TestMatchType::test(*core, *mol, params, expected);
core = "C1CCCC[*:2]1[*:1]"_smiles;
params.allowNonTerminalRGroups = true;
TestMatchType::test(*core, *mol, params, expected);
}
}
void testUnlabelledRGroupsOnAromaticNitrogen() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "Test unlabelled R groups on aromatic nitrogens"
<< std::endl;
auto core = "c1ccc(-c2cccc3[nH]ncc23)nc1"_smiles;
auto mol1 = "c1ccc(-c2cccc3n(C)ncc23)nc1"_smiles;
auto mol2 = "c1ccc(-c2cccc3[nH]ncc23)[n+](CC)c1"_smiles;
RGroupDecompositionParameters params;
RGroupDecomposition decomp(*core, params);
TEST_ASSERT(decomp.add(*mol1) == 0);
TEST_ASSERT(decomp.add(*mol2) == 1);
TEST_ASSERT(decomp.process());
auto rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 2);
size_t i = 0;
std::vector<std::string> expected{
"Core:c1ccc(-c2cccc3c2cnn3[*:2])nc1 R2:C[*:2]",
"Core:c1cc[n+]([*:1])c(-c2cccc3c2cnn3[*:2])c1 R1:CC[*:1] R2:[H][*:2]",
};
for (RGroupRows::const_iterator it = rows.begin(); it != rows.end(); ++it) {
CHECK_RGROUP(it, expected.at(i++));
}
}
void testAddHsDoesNotFail() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "Test that AddHs does not fail" << std::endl;
auto core = "[1*]c1ccc([2*])cn1"_smiles;
auto mol = "Fc1ccc([2*])cn1"_smiles;
RGroupDecompositionParameters params;
RGroupDecomposition decomp(*core, params);
TEST_ASSERT(decomp.add(*mol) == 0);
}
void testNoTempLabels() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "Test that temp labels are removed from results"
<< std::endl;
auto core = "[1*]c1ccccc1"_smiles;
auto mol = "Cc1ccccc1"_smiles;
RGroupDecompositionParameters params;
RGroupDecomposition decomp(*core, params);
TEST_ASSERT(decomp.add(*mol) == 0);
TEST_ASSERT(decomp.process());
auto rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1);
const auto &res = rows.front();
for (const auto &pair : res) {
for (const auto a : pair.second->atoms()) {
for (const auto &propName : a->getPropList()) {
TEST_ASSERT(propName.find("label") == std::string::npos);
}
}
}
}
void testNoSideChains() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "Test the no side chain return code" << std::endl;
auto core = "[H]C([H])([H])[H]"_smarts;
auto mol = "C"_smiles;
RGroupDecompositionParameters params;
RGroupDecomposition decomp(*core, params);
TEST_ASSERT(decomp.add(*mol) == -2);
}
void testDoNotAddUnnecessaryRLabels() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "Test that R labels are not added if not necessary"
<< std::endl;
{
auto m1 = "c1c(F)cccn1"_smiles;
auto m2 = "c1c(Cl)c(C)ccn1"_smiles;
auto m3 = "c1c(O)cccn1"_smiles;
auto m4 = "c1cc(C)c(F)cn1"_smiles;
auto core = "c1c([*:1])c([*:2])ccn1"_smiles;
// the test runs twice, with and without symmetrization
// results should be the same as do not depend on permutations
for (unsigned int i = 0; i < 2; ++i) {
RGroupDecompositionParameters ps;
if (i) {
ps.matchingStrategy = RDKit::NoSymmetrization;
}
RGroupDecomposition decomp(*core, ps);
TEST_ASSERT(decomp.add(*m1) == 0);
TEST_ASSERT(decomp.add(*m2) == 1);
TEST_ASSERT(decomp.add(*m3) == 2);
TEST_ASSERT(decomp.add(*m4) == 3);
decomp.process();
std::stringstream ss;
auto groups = decomp.getRGroupsAsColumns();
std::set<std::string> r_labels;
for (auto &column : groups) {
r_labels.insert(column.first);
ss << "Rgroup===" << column.first << std::endl;
for (auto &rgroup : column.second) {
ss << MolToSmiles(*rgroup) << std::endl;
}
}
// We only want two groups added
TEST_ASSERT(r_labels == std::set<std::string>({"Core", "R1", "R2"}));
TEST_ASSERT(groups.size() == 3);
TEST_ASSERT(ss.str() == R"RES(Rgroup===Core
c1cc([*:2])c([*:1])cn1
c1cc([*:2])c([*:1])cn1
c1cc([*:2])c([*:1])cn1
c1cc([*:2])c([*:1])cn1
Rgroup===R1
F[*:1]
Cl[*:1]
O[*:1]
F[*:1]
Rgroup===R2
[H][*:2]
C[*:2]
[H][*:2]
C[*:2]
)RES");
}
}
{
auto cores = std::vector<ROMOL_SPTR>{"[*:1]c1ccccc1"_smiles,
"[*:1]c1c([*:2])ccc(F)c1"_smiles};
auto m1 = "Cc1c(Cl)ccc(F)c1"_smiles;
auto m2 = "Cc1c(Br)cccc1"_smiles;
size_t i;
RGroupRows rows;
RGroupDecomposition decomp(cores);
TEST_ASSERT(decomp.add(*m1) == 0);
decomp.process();
rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1);
std::vector<std::string> expected1{
"Core:Fc1ccc([*:2])c([*:1])c1 R1:C[*:1] R2:Cl[*:2]"};
i = 0;
for (RGroupRows::const_iterator it = rows.begin(); it != rows.end(); ++it) {
CHECK_RGROUP(it, expected1.at(i++));
}
TEST_ASSERT(decomp.add(*m2) == 1);
decomp.process();
rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 2);
std::vector<std::string> expected2{
"Core:Fc1ccc([*:2])c([*:1])c1 R1:C[*:1] R2:Cl[*:2]",
"Core:c1ccc([*:3])c([*:1])c1 R1:C[*:1] R3:Br[*:3]"};
i = 0;
for (RGroupRows::const_iterator it = rows.begin(); it != rows.end(); ++it) {
CHECK_RGROUP(it, expected2.at(i++));
}
}
{
auto cores = std::vector<ROMOL_SPTR>{"[*:1]c1c([*:2])ccc(F)c1"_smiles,
"[*:1]c1ccccc1"_smiles,
"[*:1]c1c([*:2])cccc1"_smiles};
auto mols = std::vector<ROMOL_SPTR>{
"Cc1c(Cl)ccc(F)c1"_smiles, "Cc1c(Cl)ccc(N)c1"_smiles,
"Cc1ccccc1"_smiles, "Cc1c(Br)cccc1"_smiles, "Cc1cc(F)ccc1"_smiles};
RGroupRows rows;
RGroupDecomposition decomp(cores);
int n = 0;
for (const auto &m : mols) {
TEST_ASSERT(decomp.add(*m) == n++);
}
decomp.process();
rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 5);
std::vector<std::string> expected{
"Core:Fc1ccc([*:2])c([*:1])c1 R1:C[*:1] R2:Cl[*:2]",
"Core:c1cc([*:2])c([*:1])cc1[*:3] R1:C[*:1] R2:Cl[*:2] R3:N[*:3]",
"Core:c1cc([*:1])cc([*:3])c1 R1:C[*:1] R3:[H][*:3]",
"Core:c1cc([*:2])c([*:1])cc1[*:3] R1:C[*:1] R2:Br[*:2] R3:[H][*:3]",
"Core:Fc1ccc([*:2])c([*:1])c1 R1:C[*:1] R2:[H][*:2]"};
size_t i = 0;
for (RGroupRows::const_iterator it = rows.begin(); it != rows.end(); ++it) {
CHECK_RGROUP(it, expected.at(i++));
}
}
}
void testCoreWithAlsRecords() {
auto core = R"CTAB(
Mrv2008 11112113312D
6 6 6 0 0 0 999 V2000
-13.7277 2.6107 0.0000 L 0 0 0 0 0 0 0 0 0 0 0 0
-14.4421 2.1982 0.0000 L 0 0 0 0 0 0 0 0 0 0 0 0
-14.4421 1.3732 0.0000 L 0 0 0 0 0 0 0 0 0 0 0 0
-13.7277 0.9607 0.0000 L 0 0 0 0 0 0 0 0 0 0 0 0
-13.0132 1.3732 0.0000 L 0 0 0 0 0 0 0 0 0 0 0 0
-13.0132 2.1982 0.0000 L 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0 0 0 0
2 3 2 0 0 0 0
3 4 1 0 0 0 0
4 5 2 0 0 0 0
5 6 1 0 0 0 0
1 6 2 0 0 0 0
1 F 2 6 7
2 F 2 6 7
3 F 2 6 7
4 F 2 6 7
5 F 2 6 7
6 F 2 6 7
M ALS 1 2 F C N
M ALS 2 2 F C N
M ALS 3 2 F C N
M ALS 4 2 F C N
M ALS 5 2 F C N
M ALS 6 2 F C N
M END
)CTAB"_ctab;
TEST_ASSERT(core);
std::string sma = MolToSmarts(*core);
TEST_ASSERT(sma == "[#6,#7]1:[#6,#7]:[#6,#7]:[#6,#7]:[#6,#7]:[#6,#7]:1");
auto structure = "ClC1=CN=C(C=C1)N1CCCC1"_smiles;
RGroupDecomposition decomp(*core);
TEST_ASSERT(decomp.add(*structure) == 0);
decomp.process();
auto rows = decomp.getRGroupsAsRows();
auto core_out = rows[0]["Core"];
auto core_mol_block = MolToMolBlock(*rows[0]["Core"]);
auto pos = core_mol_block.find("ALS");
TEST_ASSERT(pos == std::string::npos);
std::string expected(
"Core:c1cc([*:2])ncc1[*:1] R1:Cl[*:1] R2:C1CCN([*:2])C1");
RGroupRows::const_iterator it = rows.begin();
CHECK_RGROUP(it, expected);
}
void testAlignOutputCoreToMolecule() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "Test that output core is aligned to input molecule"
<< std::endl;
struct Helper {
static RDGeom::Point3D findPointForAtomNumber(const ROMol &mol,
int atomNumber) {
for (const auto atom : mol.atoms()) {
if (atom->getAtomicNum() == atomNumber) {
return mol.getConformer().getAtomPos(atom->getIdx());
}
}
throw std::runtime_error("Can't find atom in molecule");
}
};
auto core = R"CTAB(
Mrv2008 11162112382D
15 16 0 0 0 0 999 V2000
-13.4365 2.6419 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-13.0116 1.9347 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-12.1867 1.9491 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-11.7867 2.6706 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-12.2116 3.3778 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-13.0365 3.3634 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-10.9618 2.6850 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-10.5619 3.4066 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-9.7370 3.4210 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-10.5369 1.9779 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
-9.3121 4.1282 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-9.3370 2.6994 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-8.5121 2.6850 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-8.0873 3.3922 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-8.4872 4.1138 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1 2 2 0 0 0 0
3 4 2 0 0 0 0
5 6 2 0 0 0 0
4 5 1 0 0 0 0
2 3 1 0 0 0 0
1 6 1 0 0 0 0
4 7 1 0 0 0 0
7 8 1 0 0 0 0
8 9 1 0 0 0 0
7 10 2 0 0 0 0
12 13 1 0 0 0 0
13 14 2 0 0 0 0
14 15 1 0 0 0 0
11 15 2 0 0 0 0
11 9 1 0 0 0 0
9 12 2 0 0 0 0
M END
)CTAB"_ctab;
auto mol = R"CTAB(
-OEChem-03051316302D
19 21 0 0 0 0 0 0 0999 V2000
-1.7593 5.0073 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.6211 4.4999 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.6183 3.4999 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.7450 3.0022 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.8744 3.5045 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.8860 4.5096 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.7423 2.0022 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.6070 1.4999 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
-0.8750 1.5045 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-0.8723 0.5045 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.0000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.0013 -1.0057 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.8697 -1.5068 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.7364 -1.0079 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.7377 -0.0022 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.6056 0.5056 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.4735 -0.0022 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.4735 -1.0079 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.6056 -1.5057 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1 6 2 0 0 0 0
1 2 1 0 0 0 0
2 3 2 0 0 0 0
3 4 1 0 0 0 0
4 5 2 0 0 0 0
5 6 1 0 0 0 0
4 7 1 0 0 0 0
7 8 2 0 0 0 0
7 9 1 0 0 0 0
9 10 1 0 0 0 0
10 15 2 0 0 0 0
10 11 1 0 0 0 0
11 12 2 0 0 0 0
12 13 1 0 0 0 0
13 14 2 0 0 0 0
14 19 1 0 0 0 0
14 15 1 0 0 0 0
15 16 1 0 0 0 0
16 17 2 0 0 0 0
17 18 1 0 0 0 0
18 19 2 0 0 0 0
M END
)CTAB"_ctab;
RGroupRows rows;
RGroupDecomposition decomp(*core);
TEST_ASSERT(decomp.add(*mol) == 0);
decomp.process();
rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1)
auto coreOut = rows[0]["Core"];
for (int atomNumber = 7; atomNumber <= 8; atomNumber++) {
const auto &coreInPoint = Helper::findPointForAtomNumber(*core, atomNumber);
const auto &molInPoint = Helper::findPointForAtomNumber(*mol, atomNumber);
const auto &coreOutPoint =
Helper::findPointForAtomNumber(*coreOut, atomNumber);
TEST_ASSERT(fabs(coreInPoint.x - molInPoint.x) > 0.25);
TEST_ASSERT(fabs(coreOutPoint.x - molInPoint.x) < 1e-10);
TEST_ASSERT(fabs(coreInPoint.y - molInPoint.y) > 0.25);
TEST_ASSERT(fabs(coreOutPoint.y - molInPoint.y) < 1e-10);
}
}
void testWildcardInInput() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog)
<< "Test that dummy atom in input molecule is handled correctly"
<< std::endl;
auto core = R"CTAB(
Mrv2008 12012115162D
6 6 6 0 0 0 999 V2000
-21.0938 -16.9652 0.0000 L 0 0 0 0 0 0 0 0 0 0 0 0
-21.8082 -17.3777 0.0000 L 0 0 0 0 0 0 0 0 0 0 0 0
-21.8082 -18.2027 0.0000 L 0 0 0 0 0 0 0 0 0 0 0 0
-21.0938 -18.6152 0.0000 L 0 0 0 0 0 0 0 0 0 0 0 0
-20.3793 -18.2027 0.0000 L 0 0 0 0 0 0 0 0 0 0 0 0
-20.3793 -17.3777 0.0000 L 0 0 0 0 0 0 0 0 0 0 0 0
1 2 6 0 0 0 0
2 3 7 0 0 0 0
3 4 6 0 0 0 0
4 5 7 0 0 0 0
5 6 6 0 0 0 0
1 6 7 0 0 0 0
1 F 2 6 7
2 F 2 6 7
3 F 2 6 7
4 F 2 6 7
5 F 2 6 7
6 F 2 6 7
M ALS 1 2 F C N
M ALS 2 2 F C N
M ALS 3 2 F C N
M ALS 4 2 F C N
M ALS 5 2 F C N
M ALS 6 2 F C N
M END
)CTAB"_ctab;
auto structure = "CC1CCN(C1)C1=CC(O*)=C(Cl)C=C1C#N"_smiles;
RGroupDecomposition decomp(*core);
TEST_ASSERT(decomp.add(*structure) == 0);
decomp.process();
auto rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1)
RGroupRows::const_iterator it = rows.begin();
std::string expected(
"Core:c1c([*:2])c([*:1])cc([*:4])c1[*:3] R1:Cl[*:1] R2:*O[*:2] "
"R3:CC1CCN([*:3])C1 R4:N#C[*:4]");
CHECK_RGROUP(it, expected);
structure = "CC1CCN(C1)C1=CC([*:2])=C(Cl)C=C1C#N"_smiles;
RGroupDecomposition decomp2(*core);
TEST_ASSERT(decomp2.add(*structure) == 0);
decomp2.process();
rows = decomp2.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1)
it = rows.begin();
expected =
"Core:c1c([*:2])c([*:1])cc([*:4])c1[*:3] R1:Cl[*:1] R2:*[*:2] "
"R3:CC1CCN([*:3])C1 R4:N#C[*:4]";
CHECK_RGROUP(it, expected);
}
void testDoNotChooseUnrelatedCores() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "Test that later cores with more R-groups\n"
<< "are only chosen if superstructures of earlier\n"
<< "cores" << std::endl;
{
// 1st test, two unrelated cores:
// 1) 5 terms, 1 R-group
// 2) 6 terms, 3 R-groups
// dataset molecule can fit core 1 adding 1 non-user defined R label,
// and core 2 with no addition of R labels
ROMOL_SPTR core5Terms1RGroup = "[*:1]C1COCN1"_smiles;
ROMOL_SPTR core6Terms3RGroups = "[*:1]c1ccc([*:2])c([*:3])c1"_smiles;
std::vector<ROMOL_SPTR> cores{core5Terms1RGroup, core6Terms3RGroups};
auto m = "Cc1cc(ccc1F)C1NC(CO1)c1cccs1"_smiles;
// repeat the test twice, with cores in opposite orders
// in both cases core ordering should be honored and the first
// core (either 5-term of 6-term) should be chosen, even when adding
// R labels is required, as the 2 cores are not structurally related
for (unsigned int i = 0; i < 2; ++i) {
std::vector<ROMOL_SPTR> orderedCores{cores[i], cores[1 - i]};
RGroupDecomposition decomp(orderedCores);
TEST_ASSERT(decomp.add(*m) == 0);
TEST_ASSERT(decomp.process());
auto cols = decomp.getRGroupsAsColumns();
const auto &core = cols["Core"];
TEST_ASSERT(core.size() == 1);
TEST_ASSERT(
core.front()->getRingInfo()->atomRings().front().size() ==
orderedCores.front()->getRingInfo()->atomRings().front().size());
}
}
{
// 2nd test: two related cores:
// 1) 5 terms, 2 R-groups
// 2) 5 terms, 3 R-groups
// dataset molecule 1 has 1 substituent, fits both cores
// dataset molecule 2 has 2 substituents, fits both cores
// dataset molecule 3 has 3 substituents, fits core 2 with no need to add
// R labels
ROMOL_SPTR core5Terms2RGroups = "[*:1]C1COC([*:2])N1"_smiles;
ROMOL_SPTR core5Terms3RGroups = "[*:1]C1C([*:2])OC([*:3])N1"_smiles;
std::vector<ROMOL_SPTR> cores{core5Terms2RGroups, core5Terms3RGroups};
std::vector<ROMOL_SPTR> mols{"CC1NCCO1"_smiles, "CC1NC(F)CO1"_smiles,
"CC1NC(F)C(Cl)O1"_smiles};
// repeat the test twice, with cores in opposite orders
// Molecules (1) and (2) should always pick the first core
// in the order provided, though both cores could fit
// Molecule (3) should always pick the more specific core 2
for (unsigned int i = 0; i < 2; ++i) {
std::vector<ROMOL_SPTR> orderedCores{cores[i], cores[1 - i]};
RGroupDecomposition decomp(orderedCores);
int j = 0;
for (const auto &m : mols) {
TEST_ASSERT(decomp.add(*m) == j++);
}
TEST_ASSERT(decomp.process());
auto cols = decomp.getRGroupsAsColumns();
const auto &core = cols["Core"];
TEST_ASSERT(core.size() == 3);
TEST_ASSERT(MolToSmiles(*core.at(0)) ==
MolToSmiles(*orderedCores.front()));
TEST_ASSERT(MolToSmiles(*core.at(1)) ==
MolToSmiles(*orderedCores.front()));
TEST_ASSERT(MolToSmiles(*core.at(2)) == MolToSmiles(*core5Terms3RGroups));
}
}
}
void atomDegreePreconditionBug() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog)
<< "Test that we don't get a bad atom degree precondition violation when "
"the input structure has dummy atoms"
<< std::endl;
auto structure = R"CTAB(
RDKit 2D
12 12 0 0 0 0 0 0 0 0999 V2000
3.0000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1.5000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.5000 0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-0.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.7500 1.2990 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-1.5000 -2.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.0000 -2.5981 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
-0.7500 -3.8971 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
-1.5000 -5.1962 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.5000 2.5981 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0
2 3 2 0
3 4 1 0
4 5 2 0
5 6 1 0
6 7 2 0
4 8 1 0
8 9 2 0
8 10 1 0
10 11 1 0
7 2 1 0
6 12 1 0
M RGP 1 12 3
M END
)CTAB"_ctab;
auto core = "[#6]1:[#7]:[#6]:[#6]:[#6]:[#7]:1"_smarts;
RGroupDecomposition decomp(*core);
TEST_ASSERT(decomp.add(*structure) == 0);
decomp.process();
auto rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1)
RGroupRows::const_iterator it = rows.begin();
std::string expected(
"Core:c1c([*:1])nc([*:3])nc1[*:2] R1:COC(=O)[*:1] R2:C[*:2] R3:*[*:3]");
// Check R3 atom labelling
auto r3 = rows[0]["R3"];
TEST_ASSERT(r3->getNumAtoms() == 2)
TEST_ASSERT(r3->getAtomWithIdx(0)->hasProp(common_properties::dummyLabel));
TEST_ASSERT(r3->getAtomWithIdx(1)->hasProp(common_properties::dummyLabel));
TEST_ASSERT(r3->getAtomWithIdx(0)->getProp<std::string>(
common_properties::dummyLabel) == "*");
TEST_ASSERT(r3->getAtomWithIdx(1)->getProp<std::string>(
common_properties::dummyLabel) == "R3");
CHECK_RGROUP(it, expected);
}
void testGithub5222() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "Test that Github5222 is fixed" << std::endl;
auto core = R"CTAB(
ChemDraw04112214222D
6 6 3 0 0 0 0 0 0 0999 V2000
-0.7145 0.4125 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.7145 -0.4125 0.0000 L 0 0 0 0 0 0 0 0 0 0 0 0
0.0000 -0.8250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.7145 -0.4125 0.0000 L 0 0 0 0 0 0 0 0 0 0 0 0
0.7145 0.4125 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.0000 0.8250 0.0000 L 0 0 0 0 0 0 0 0 0 0 0 0
1 2 2 0
2 3 1 0
3 4 2 0
4 5 1 0
5 6 2 0
6 1 1 0
2 F 2 6 7
4 F 2 6 7
6 F 2 6 7
M ALS 2 2 F C N
M ALS 4 2 F C N
M ALS 6 2 F C N
M END
)CTAB"_ctab;
std::vector<std::string> smiArray(10, "COc1ccccc1");
smiArray.push_back("COc1ccncn1");
RGroupDecompositionParameters params;
params.matchingStrategy = GreedyChunks;
RGroupDecomposition decomp(*core, params);
for (const auto &smiles : smiArray) {
ROMol *mol = SmilesToMol(smiles);
int res = decomp.add(*mol);
TEST_ASSERT(res >= 0);
delete mol;
}
decomp.process();
std::cerr << "Best mapping" << std::endl;
RGroupRows rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 11);
for (const auto &row : rows) {
TEST_ASSERT(row.size() == 2);
TEST_ASSERT(row.count("Core") == 1);
TEST_ASSERT(row.count("R1") == 1);
auto mol = row.at("R1");
auto groupSmiles = MolToSmiles(*mol);
TEST_ASSERT(groupSmiles == "CO[*:1]");
}
}
void testGithub5569() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "Test that Github5269 is fixed" << std::endl;
auto core = R"CTAB(
ChemDraw09152209202D
6 6 0 0 0 0 0 0 0 0999 V2000
0.0001 0.8250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.7144 0.4125 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.7144 -0.4125 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.0001 -0.8250 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
0.7144 -0.4125 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.7144 0.4125 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0
2 3 1 0
3 4 1 0
4 5 1 0
5 6 1 0
6 1 1 0
M END
)CTAB"_ctab;
auto test = R"CTAB(
RDKit 2D
20 21 0 0 0 0 0 0 0 0999 V2000
-2.6437 1.7625 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.3582 1.3500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.3582 0.5250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.6438 0.1125 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-1.9293 0.5250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.9293 1.3500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.2148 1.7625 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.5003 1.3500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.2141 1.7625 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.9286 1.3500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.3692 2.3459 0.0000 F 0 0 0 0 0 0 0 0 0 0 0 0
0.7975 2.3459 0.0000 F 0 0 0 0 0 0 0 0 0 0 0 0
-2.6438 -0.7125 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.3582 -1.1250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.3582 -1.9500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.6438 -2.3625 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.9293 -1.9500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.9293 -1.1250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.2271 -2.9459 0.0000 F 0 0 0 0 0 0 0 0 0 0 0 0
-2.0604 -2.9459 0.0000 F 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0
2 3 1 0
3 4 1 0
4 5 1 0
5 6 1 0
6 1 1 0
6 7 1 0
7 8 1 0
8 9 1 0
9 10 1 0
9 11 1 0
9 12 1 0
4 13 1 0
13 14 1 0
14 15 1 0
15 16 1 0
16 17 1 0
17 18 1 0
18 13 1 0
16 19 1 0
16 20 1 0
M END
)CTAB"_ctab;
RGroupDecompositionParameters params;
params.matchingStrategy = GreedyChunks;
RGroupDecomposition decomp(*core, params);
decomp.add(*test);
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1)
auto r2 = rows[0]["R2"];
auto match = std::find_if(r2->atoms().begin(), r2->atoms().end(),
[](Atom *a) { return a->getAtomicNum() == 0; });
auto dummy = *match;
int neighborIndex = *r2->getAtomNeighbors(dummy).first;
auto conf = r2->getConformer();
auto p1 = conf.getAtomPos(dummy->getIdx());
auto p2 = conf.getAtomPos(neighborIndex);
auto length = (p1 - p2).length();
TEST_ASSERT(fabs(length - 1.0) < 0.25);
}
void testMultipleGroupsToUnlabelledCoreAtomGithub5573() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "Test that Github5573 is fixed" << std::endl;
auto core = R"CTAB(
Mrv2008 09172211422D
8 8 0 0 0 0 999 V2000
-7.2098 -3.1928 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-7.9243 -3.6053 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-7.9243 -4.4304 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-7.2098 -4.8429 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-6.4954 -4.4304 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-6.4954 -3.6053 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-5.7809 -4.8429 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
-5.0664 -4.4304 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0 0 0 0
2 3 1 0 0 0 0
3 4 1 0 0 0 0
4 5 1 0 0 0 0
5 6 1 0 0 0 0
1 6 1 0 0 0 0
5 7 1 0 0 0 0
7 8 1 0 0 0 0
M END
)CTAB"_ctab;
auto test = R"CTAB(
Mrv2008 09172211422D
10 10 0 0 0 0 999 V2000
-2.6437 1.7625 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.3582 1.3500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.3582 0.5250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.6438 0.1125 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-1.9293 0.5250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.9293 1.3500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-4.1730 1.4791 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.5085 2.1612 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.2148 0.1125 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
-0.5004 0.5250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0 0 0 0
2 3 1 0 0 0 0
3 4 1 0 0 0 0
4 5 1 0 0 0 0
5 6 1 0 0 0 0
6 1 1 0 0 0 0
2 7 1 0 0 0 0
2 8 1 0 0 0 0
5 9 1 0 0 0 0
9 10 1 0 0 0 0
M END
)CTAB"_ctab;
RGroupDecompositionParameters params;
params.matchingStrategy = GreedyChunks;
params.allowMultipleRGroupsOnUnlabelled = true;
RGroupDecomposition decomp(*core, params);
auto result = decomp.add(*test);
TEST_ASSERT(result == 0);
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1)
auto row = rows[0];
std::string expected("Core:COC1CCC([*:1])([*:2])CN1 R1:C[*:1] R2:C[*:2]");
RGroupRows::const_iterator it = rows.begin();
CHECK_RGROUP(it, expected);
}
void testGithub4505() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "Test GitHub 4505 is fixed" << std::endl;
{
// this is the first example from issue 4505- I have changed it so that the
// molecule is not an exact match to the core (if no sidechains are found
// the decomposition fails)
auto core = "[n]1([*:1])cc([*:2])ccc1"_smarts;
auto mol = "n1cc(OC)ccc1"_smiles;
RGroupDecompositionParameters params;
params.removeAllHydrogenRGroups = false;
RGroupDecomposition decomp(*core, params);
auto result = decomp.add(*mol);
TEST_ASSERT(result == 0)
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1)
auto row = rows[0];
std::string expected("Core:c1cncc([*:2])c1 R2:CO[*:2]");
RGroupRows::const_iterator it = rows.begin();
CHECK_RGROUP(it, expected);
}
{
// This is the second example from issue 5505. The core is not listed in
// the example code so this is my guess
auto core = "[#6]([*:1])([*:2])~1~[#6]~[#6]~[#6]~[#6]~[#6]~1"_smarts;
auto mol = "C=1(C)CCCCC1"_smiles;
RGroupDecompositionParameters params;
params.removeAllHydrogenRGroups = false;
RGroupDecomposition decomp(*core, params);
auto result = decomp.add(*mol);
TEST_ASSERT(result == 0)
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1)
auto row = rows[0];
std::string expected("Core:C1=C([*:1])CCCC1 R1:C[*:1]");
RGroupRows::const_iterator it = rows.begin();
CHECK_RGROUP(it, expected);
}
}
void testMultipleGroupsToUnlabelledCoreAtom() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "Test unlabeled core atom issues" << std::endl;
{
// Sulfonamide example
auto core = "[#6]-1-[#6]-[#6]-[#6]-[#7]-[#16]-1"_smarts;
auto mol = "O=S1(=O)CCCCN1"_smiles;
RGroupDecompositionParameters params;
params.allowMultipleRGroupsOnUnlabelled = true;
RGroupDecomposition decomp(*core, params);
auto result = decomp.add(*mol);
TEST_ASSERT(result == 0)
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1)
auto row = rows[0];
std::string expected("Core:C1CCS(=[*:1])(=[*:2])NC1 R1:O=[*:1] R2:O=[*:2]");
RGroupRows::const_iterator it = rows.begin();
CHECK_RGROUP(it, expected);
}
{
// Smiles/smarts version of github 5573
auto core = "[#6]-[#8]-[#6]-1-[#6]-[#6]-[#6]-[#6]-[#7]-1"_smarts;
auto mol = "COC1CCC(C)(C)CN1"_smiles;
RGroupDecompositionParameters params;
params.allowMultipleRGroupsOnUnlabelled = true;
RGroupDecomposition decomp(*core, params);
auto result = decomp.add(*mol);
TEST_ASSERT(result == 0)
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1)
auto row = rows[0];
std::string expected("Core:COC1CCC([*:1])([*:2])CN1 R1:C[*:1] R2:C[*:2]");
RGroupRows::const_iterator it = rows.begin();
CHECK_RGROUP(it, expected);
}
{
// Check that sidechains cluster properly
auto core = "[#6]-[#8]-[#6]-1-[#6]-[#6]-[#6]-[#6]-[#7]-1"_smarts;
std::vector<std::string> smilesVec{
"COC1CCC(C)(C)CN1", "COC1CCC(CC)(C)CN1", "COC1CCC(C)(COC)CN1",
"COC1CCC(C)(OC)CN1", "COC1CCC(CCC)(C)CN1"};
RGroupDecompositionParameters params;
params.allowMultipleRGroupsOnUnlabelled = true;
params.matchingStrategy = Exhaustive;
params.scoreMethod = FingerprintVariance;
RGroupDecomposition decomp(*core, params);
for (auto smiles : smilesVec) {
auto mol = SmilesToMol(smiles);
auto result = decomp.add(*mol);
TEST_ASSERT(result > -1);
delete mol;
}
decomp.process();
auto rows = decomp.getRGroupsAsRows();
std::vector<std::string> expected{
"Core:COC1CCC([*:1])([*:2])CN1 R1:C[*:1] R2:C[*:2]",
"Core:COC1CCC([*:1])([*:2])CN1 R1:CC[*:1] R2:C[*:2]",
"Core:COC1CCC([*:1])([*:2])CN1 R1:COC[*:1] R2:C[*:2]",
"Core:COC1CCC([*:1])([*:2])CN1 R1:CO[*:1] R2:C[*:2]",
"Core:COC1CCC([*:1])([*:2])CN1 R1:CCC[*:1] R2:C[*:2]"};
TEST_ASSERT(rows.size() == expected.size());
int i = 0;
for (auto row = rows.cbegin(); row != rows.cend(); ++row, ++i) {
CHECK_RGROUP(row, expected[i]);
}
}
{
// Check core with terminal wildcard - dummy atom labels allowed
auto core = "[*]-[#8]-[#6]-1-[#6]-[#6]-[#6]-[#6]-[#7]-1"_smarts;
auto mol = "COC1CCC(C)(C)CN1"_smiles;
RGroupDecompositionParameters params;
params.allowMultipleRGroupsOnUnlabelled = true;
params.labels = DummyAtomLabels;
RGroupDecomposition decomp(*core, params);
auto result = decomp.add(*mol);
TEST_ASSERT(result == 0)
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1)
auto row = rows[0];
std::string expected(
"Core:C1CC([*:2])([*:3])CNC1O[*:1] R1:C[*:1] R2:C[*:2] R3:C[*:3]");
RGroupRows::const_iterator it = rows.begin();
CHECK_RGROUP(it, expected);
// Check core with terminal wildcard - dummy atom labels not allowed
params.labels = IsotopeLabels;
RGroupDecomposition decomp2(*core, params);
result = decomp2.add(*mol);
TEST_ASSERT(result == 0)
decomp2.process();
rows = decomp2.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1)
row = rows[0];
std::string expected2("Core:COC1CCC([*:1])([*:2])CN1 R1:C[*:1] R2:C[*:2]");
it = rows.begin();
CHECK_RGROUP(it, expected2);
}
{
// Check core with wildcard in ring
auto core = "[#6]-[#8]-[#6]-1-[#7]-[#6]-[#6]-[#6]-[*]-1"_smarts;
std::vector<std::string> smilesVec{"COC1CCC(C)(C)CN1", "COC1NCC(C)(C)CO1",
"COC1NCC(C)(C)CN1"};
RGroupDecompositionParameters params;
params.allowMultipleRGroupsOnUnlabelled = true;
params.matchingStrategy = Exhaustive;
params.scoreMethod = FingerprintVariance;
RGroupDecomposition decomp(*core, params);
for (auto smiles : smilesVec) {
auto mol = SmilesToMol(smiles);
auto result = decomp.add(*mol);
TEST_ASSERT(result > -1);
delete mol;
}
decomp.process();
auto rows = decomp.getRGroupsAsRows();
std::vector<std::string> expected{
"Core:COC1CCC([*:1])([*:2])CN1 R1:C[*:1] R2:C[*:2]",
"Core:COC1NCC([*:1])([*:2])CO1 R1:C[*:1] R2:C[*:2]",
"Core:COC1NCC([*:1])([*:2])CN1 R1:C[*:1] R2:C[*:2]"};
TEST_ASSERT(rows.size() == expected.size());
int i = 0;
for (auto row = rows.cbegin(); row != rows.cend(); ++row, ++i) {
CHECK_RGROUP(row, expected[i]);
}
}
}
void testGithub5613() {
{
// Original issue from 5613
auto core = "[*:1]C(=O)NC1CCN([*:3])C1"_smarts;
auto mol =
"Cc1c(c(c([nH]1)C(=O)N[C@H]2CCN(C2)c3cc(nc(n3)Cl)C(=O)O)Cl)Cl"_smiles;
RGroupDecompositionParameters params;
params.allowMultipleRGroupsOnUnlabelled = false;
RGroupDecomposition decomp(*core, params);
auto result = decomp.add(*mol);
TEST_ASSERT(result == 0)
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1)
auto row = rows[0];
std::string expected(
"Core:O=C(N[C@H]1CCN([*:3])C1)[*:1] "
"R1:Cc1[nH]c([*:1])c(Cl)c1Cl "
"R3:O=C(O)c1cc([*:3])nc(Cl)n1");
RGroupRows::const_iterator it = rows.begin();
CHECK_RGROUP(it, expected);
}
{
auto core = "[1*]C(=O)*C1~C~C~*([3*])~*~C~1[2*]"_smarts;
auto mol =
"CO[C@H]1CN(c2nc(-c3cnc(OCCN4CCN(C)CC4)cn3)c(C(=O)O)s2)CC[C@H]1NC(=O)c1[nH]c(C)c(Cl)c1Cl"_smiles;
RGroupDecompositionParameters params;
params.allowMultipleRGroupsOnUnlabelled = false;
RGroupDecomposition decomp(*core, params);
auto result = decomp.add(*mol);
TEST_ASSERT(result == 0)
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1)
auto row = rows[0];
std::string expected(
"Core:O=C(N[C@@H]1CCN([*:3])C[C@@H]1[*:2])[*:1] "
"R1:Cc1[nH]c([*:1])c(Cl)c1Cl R2:CO[*:2] "
"R3:CN1CCN(CCOc2cnc(-c3nc([*:3])sc3C(=O)O)cn2)CC1");
RGroupRows::const_iterator it = rows.begin();
CHECK_RGROUP(it, expected);
}
{
auto core = "C(=O)*C1~C~C~*~*~C~1"_smarts;
auto mol =
"CO[C@H]1CN(c2nc(-c3cnc(OCCN4CCN(C)CC4)cn3)c(C(=O)O)s2)CC[C@H]1NC(=O)c1[nH]c(C)c(Cl)c1Cl"_smiles;
RGroupDecompositionParameters params;
params.allowMultipleRGroupsOnUnlabelled = true;
RGroupDecomposition decomp(*core, params);
auto result = decomp.add(*mol);
TEST_ASSERT(result == 0)
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1)
auto row = rows[0];
std::string expected(
"Core:O=C(N[C@@H]1CCN([*:1])C[C@@H]1[*:2])[*:3] "
"R1:CN1CCN(CCOc2cnc(-c3nc([*:1])sc3C(=O)O)cn2)CC1 "
"R2:CO[*:2] R3:Cc1[nH]c([*:3])c(Cl)c1Cl");
RGroupRows::const_iterator it = rows.begin();
CHECK_RGROUP(it, expected);
}
}
void testGitHub5631() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog)
<< "Test that Github563 (proper placement of core R groups) is fixed"
<< std::endl;
auto core = R"CTAB(
RDKit 2D
12 12 0 0 0 0 0 0 0 0999 V2000
-3.4154 3.2137 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.5903 3.2137 0.0000 A 0 0 0 0 0 0 0 0 0 0 0 0
-2.1778 3.9282 0.0000 A 0 0 0 0 0 0 0 0 0 0 0 0
-2.5903 4.6427 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.4154 4.6427 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.8278 3.9282 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-4.6528 3.9282 0.0000 A 0 0 0 0 0 0 0 0 0 0 0 0
-3.8278 2.4993 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0
-1.3528 3.9282 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0
-5.0654 4.6427 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-4.6528 5.3572 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
-5.8904 4.6427 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0
5 6 8 0
4 5 8 0
3 4 8 0
2 3 8 0
1 2 8 0
1 6 8 0
6 7 1 0
1 8 1 0
3 9 1 0
7 10 1 0
10 11 2 0
10 12 1 0
M ISO 3 8 2 9 3 12 1
M RGP 3 8 2 9 3 12 1
M END
)CTAB"_ctab;
auto mol1 = R"CTAB(
-OEChem-02051811442D
25 27 0 0 0 0 0 0 0999 V2000
-0.8675 0.4975 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.0000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.8675 0.4975 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.8675 1.5027 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.0000 2.0104 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-0.8675 1.5027 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1.7350 2.0001 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
2.6070 1.5001 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
3.4790 2.0002 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
3.4790 3.0002 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
2.6159 3.5053 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1.7439 3.0052 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
4.3465 3.4976 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
4.3495 4.4976 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
3.4849 5.0002 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
5.2170 4.9951 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
6.1281 4.5828 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
6.8007 5.3248 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
6.3049 6.1952 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
5.3214 5.9901 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
6.7160 7.1067 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0
7.7947 5.2157 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0
1.7328 -0.0038 0.0000 N 0 3 0 0 0 0 0 0 0 0 0 0
1.7313 -1.0038 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
2.5995 0.4950 0.0000 O 0 5 0 0 0 0 0 0 0 0 0 0
1 6 2 0 0 0 0
1 2 1 0 0 0 0
2 3 2 0 0 0 0
3 4 1 0 0 0 0
4 5 2 0 0 0 0
5 6 1 0 0 0 0
4 7 1 0 0 0 0
7 12 1 0 0 0 0
7 8 1 0 0 0 0
8 9 1 0 0 0 0
9 10 1 0 0 0 0
10 11 1 0 0 0 0
11 12 1 0 0 0 0
10 13 1 0 0 0 0
13 14 1 0 0 0 0
14 15 2 0 0 0 0
14 16 1 0 0 0 0
16 20 1 0 0 0 0
16 17 2 0 0 0 0
17 18 1 0 0 0 0
18 19 2 0 0 0 0
19 20 1 0 0 0 0
19 21 1 0 0 0 0
18 22 1 0 0 0 0
3 23 1 0 0 0 0
23 24 2 0 0 0 0
23 25 1 0 0 0 0
M CHG 2 23 1 25 -1
M END
$$$$
)CTAB"_ctab;
auto mol2 = R"CTAB(
-OEChem-02051811442D
45 49 0 1 0 0 0 0 0999 V2000
-2.9472 -3.8597 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.8765 -2.8622 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.6440 -2.2211 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.2684 -1.2927 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.2691 -1.3606 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.0260 -2.3354 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-1.6270 -0.5940 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.9700 0.3454 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
-0.6420 -0.7667 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
0.0000 0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0
1.1236 -1.3417 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0
-0.8675 0.4975 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.8675 1.5027 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.0000 2.0104 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0
0.8675 1.5027 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.8675 0.4975 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0
1.2077 -0.4429 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0
1.8525 0.6702 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
2.1954 1.6096 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.0000 3.0104 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.8098 3.5999 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-0.5017 4.5529 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.4983 4.5516 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.8122 3.6017 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0
1.0846 5.3617 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
2.0793 5.2591 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
0.6762 6.2745 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
-1.0895 5.3618 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.0889 5.2537 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.6768 6.0627 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-2.2755 6.9786 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.2762 7.0868 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.6781 6.2789 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-2.8669 7.7850 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
-3.8610 7.6760 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-4.4524 8.4824 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-5.4465 8.3734 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-6.0457 9.1803 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-7.0449 9.0708 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-7.4449 8.1542 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-6.8558 7.3461 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-5.8566 7.4557 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-8.4389 8.0452 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.7990 -0.4450 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0
-4.6141 -2.4639 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0 0 0 0
2 6 1 0 0 0 0
2 3 2 0 0 0 0
3 4 1 0 0 0 0
4 5 2 0 0 0 0
5 6 1 0 0 0 0
5 7 1 0 0 0 0
7 8 2 0 0 0 0
7 9 1 0 0 0 0
9 10 1 0 0 0 0
10 11 1 1 0 0 0
10 16 1 0 0 0 0
10 12 1 0 0 0 0
12 13 1 0 0 0 0
13 14 1 0 0 0 0
14 15 1 0 0 0 0
15 16 1 0 0 0 0
16 17 1 1 0 0 0
16 18 1 0 0 0 0
18 19 1 0 0 0 0
14 20 1 0 0 0 0
20 24 1 0 0 0 0
20 21 2 0 0 0 0
21 22 1 0 0 0 0
22 23 2 0 0 0 0
23 24 1 0 0 0 0
23 25 1 0 0 0 0
25 26 2 0 0 0 0
25 27 1 0 0 0 0
22 28 1 0 0 0 0
28 33 2 0 0 0 0
28 29 1 0 0 0 0
29 30 2 0 0 0 0
30 31 1 0 0 0 0
31 32 2 0 0 0 0
32 33 1 0 0 0 0
31 34 1 0 0 0 0
34 35 1 0 0 0 0
35 36 1 0 0 0 0
36 37 1 0 0 0 0
37 42 1 0 0 0 0
37 38 1 0 0 0 0
38 39 1 0 0 0 0
39 40 1 0 0 0 0
40 41 1 0 0 0 0
41 42 1 0 0 0 0
40 43 1 0 0 0 0
4 44 1 0 0 0 0
3 45 1 0 0 0 0
M END
)CTAB"_ctab;
RGroupDecompositionParameters params;
params.matchingStrategy = GreedyChunks;
params.allowMultipleRGroupsOnUnlabelled = false;
params.onlyMatchAtRGroups = true;
RGroupDecomposition decomp(*core, params);
auto result = decomp.add(*mol1);
TEST_ASSERT(result == 0);
result = decomp.add(*mol2);
TEST_ASSERT(result == 1);
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 2) {
auto coreRgd = rows[0]["Core"];
auto match = std::find_if(
coreRgd->atoms().begin(), coreRgd->atoms().end(), [](Atom *a) {
return a->getAtomicNum() == 0 && a->getAtomMapNum() == 2;
});
TEST_ASSERT(match != coreRgd->atoms().end());
auto dummy = *match;
auto neighbor = *coreRgd->atomNeighbors(dummy).begin();
auto &conf = coreRgd->getConformer();
auto &dummyPoint = conf.getAtomPos(dummy->getIdx());
auto &neighborPoint = conf.getAtomPos(neighbor->getIdx());
auto length = (dummyPoint - neighborPoint).length();
TEST_ASSERT(fabs(length - 1.0) < 0.005);
// R2 dummy should be directly above neighbor
TEST_ASSERT(fabs(dummyPoint.x - neighborPoint.x) < 0.05);
}
{
auto coreRgd = rows[1]["Core"];
auto match = std::find_if(
coreRgd->atoms().begin(), coreRgd->atoms().end(), [](const Atom *a) {
return a->getAtomicNum() == 0 && a->getAtomMapNum() == 2;
});
TEST_ASSERT(match != coreRgd->atoms().end());
auto dummy = *match;
auto &conf = coreRgd->getConformer();
auto &dummyPoint = conf.getAtomPos(dummy->getIdx());
// R2 dummy should be over input chiral oxygen, which is first oxygen of
// degree 2 in input mol block
auto &inputPoint = mol2->getConformer(0).getAtomPos(15);
TEST_ASSERT(fabs(dummyPoint.x - inputPoint.x) < 0.05);
TEST_ASSERT(fabs(dummyPoint.y - inputPoint.y) < 0.05);
}
}
void testRGroupCoordinatesAddedToCore() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog)
<< "Test that coordinates for R groups are properly added to core when the core has coordinates and the target does not"
<< std::endl;
auto core = R"CTAB(ACS Document 1996
ChemDraw05202112262D
17 17 0 0 0 0 0 0 0 0999 V2000
1.9511 0.6607 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
1.2362 1.0726 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0
0.5214 1.4844 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
0.8244 0.3577 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1.2375 -0.3563 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.8256 -1.0712 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.0006 -1.0719 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.4113 -1.7868 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
-0.4125 -0.3578 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.0006 0.3570 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.2375 -0.3585 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.0625 -0.3592 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
1.6481 1.7875 0.0000 R1 0 0 0 0 0 0 0 0 0 0 0 0
1.2387 -1.7853 0.0000 R2 0 0 0 0 0 0 0 0 0 0 0 0
-1.2363 -1.7875 0.0000 R3 0 0 0 0 0 0 0 0 0 0 0 0
-0.4137 1.0711 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0
2.0625 -0.3556 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0
1 2 2 0
2 3 2 0
2 4 1 0
4 10 1 0
4 5 2 0
5 6 1 0
6 7 2 0
7 8 1 0
7 9 1 0
9 10 2 0
9 11 1 0
11 12 3 0
2 13 1 0
6 14 1 0
8 15 1 0
10 16 1 0
5 17 1 0
M END
)CTAB"_ctab;
auto mol =
"Brc1cc(Br)c(Oc2ccc(cc2C#N)S(=O)(=O)Nc3ncc(Br)s3)c(c1)c4ccccc4"_smiles;
RGroupDecompositionParameters params;
params.matchingStrategy = GreedyChunks;
params.allowMultipleRGroupsOnUnlabelled = false;
params.onlyMatchAtRGroups = false;
RGroupDecomposition decomp(*core, params);
auto result = decomp.add(*mol);
TEST_ASSERT(result == 0);
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
auto coreRgd = rows[0]["Core"];
auto numberGroups = 0;
for (const auto atom : coreRgd->atoms()) {
if (int rGroupNum = atom->getAtomMapNum(); rGroupNum > 0) {
auto coreAtoms = core->atoms();
auto originalAtom = std::find_if(
coreAtoms.begin(), coreAtoms.end(), [rGroupNum](const auto &a) {
return static_cast<int>(a->getIsotope()) == rGroupNum;
});
TEST_ASSERT(originalAtom != coreAtoms.end());
const auto &originalPoint =
core->getConformer(0).getAtomPos((*originalAtom)->getIdx());
const auto &outputPoint =
coreRgd->getConformer(0).getAtomPos(atom->getIdx());
TEST_ASSERT(originalPoint.x == outputPoint.x);
TEST_ASSERT(originalPoint.y == outputPoint.y);
TEST_ASSERT(originalPoint.z == outputPoint.z);
numberGroups++;
}
}
TEST_ASSERT(numberGroups == 2);
}
void testStereoGroupsPreserved() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog)
<< "Test that stereo group information is copied from input structure to core and R groups"
<< std::endl;
auto core = R"CTAB(
ChemDraw02132309392D
0 0 0 0 0 0 V3000
M V30 BEGIN CTAB
M V30 COUNTS 10 10 0 0 1
M V30 BEGIN ATOM
M V30 1 C -1.071690 1.031297 0.000000 0
M V30 2 C -1.071690 0.206260 0.000000 0
M V30 3 C -0.357230 -0.206259 0.000000 0
M V30 4 C 0.357230 0.206260 0.000000 0
M V30 5 C 0.357230 1.031297 0.000000 0
M V30 6 C -0.357230 1.443816 0.000000 0
M V30 7 C -0.357230 -1.031297 0.000000 0
M V30 8 N 0.357230 -1.443816 0.000000 0
M V30 9 R1 -1.071690 -1.443816 0.000000 0
M V30 10 Cl 1.071690 1.443816 0.000000 0
M V30 END ATOM
M V30 BEGIN BOND
M V30 1 2 1 2
M V30 2 1 2 3
M V30 3 2 3 4
M V30 4 1 4 5
M V30 5 2 5 6
M V30 6 1 6 1
M V30 7 1 3 7
M V30 8 1 7 8 CFG=1
M V30 9 1 7 9
M V30 10 1 5 10
M V30 END BOND
M V30 END CTAB
M END
)CTAB"_ctab;
auto mol1 = R"CTAB(
ChemDraw02032311272D
0 0 0 0 0 0 V3000
M V30 BEGIN CTAB
M V30 COUNTS 16 17 0 0 1
M V30 BEGIN ATOM
M V30 1 C 0.348623 1.031250 0.000000 0
M V30 2 C 0.348623 0.206250 0.000000 0
M V30 3 C 1.063094 -0.206250 0.000000 0
M V30 4 C 1.777565 0.206250 0.000000 0
M V30 5 C 1.777565 1.031250 0.000000 0
M V30 6 C 1.063094 1.443750 0.000000 0
M V30 7 C 1.063094 -1.031250 0.000000 0
M V30 8 N 1.777565 -1.443750 0.000000 0
M V30 9 C 0.348623 -1.443750 0.000000 0
M V30 10 C -0.365848 -1.031250 0.000000 0
M V30 11 C -0.452084 -0.210769 0.000000 0
M V30 12 C -1.259056 -0.039242 0.000000 0
M V30 13 C -1.671556 -0.753713 0.000000 0
M V30 14 C -1.119523 -1.366808 0.000000 0
M V30 15 O -2.492036 -0.839949 0.000000 0
M V30 16 Cl 2.492036 1.443750 0.000000 0
M V30 END ATOM
M V30 BEGIN BOND
M V30 1 2 1 2
M V30 2 1 2 3
M V30 3 2 3 4
M V30 4 1 4 5
M V30 5 2 5 6
M V30 6 1 6 1
M V30 7 1 3 7
M V30 8 1 7 8 CFG=1
M V30 9 1 7 9
M V30 10 1 9 10
M V30 11 1 10 11
M V30 12 1 11 12
M V30 13 1 12 13
M V30 14 1 13 14
M V30 15 1 14 10
M V30 16 1 13 15 CFG=3
M V30 17 1 5 16
M V30 END BOND
M V30 BEGIN COLLECTION
M V30 MDLV30/STEABS ATOMS=(2 7 13)
M V30 END COLLECTION
M V30 END CTAB
M END
)CTAB"_ctab;
auto mol2 = R"CTAB(
ChemDraw02032311382D
0 0 0 0 0 0 V3000
M V30 BEGIN CTAB
M V30 COUNTS 18 19 0 0 0
M V30 BEGIN ATOM
M V30 1 C 0.348623 1.388485 0.000000 0
M V30 2 C 0.348623 0.563485 0.000000 0
M V30 3 C 1.063094 0.150985 0.000000 0
M V30 4 C 1.777565 0.563485 0.000000 0
M V30 5 C 1.777565 1.388485 0.000000 0
M V30 6 C 1.063094 1.800985 0.000000 0
M V30 7 C 1.063094 -0.674015 0.000000 0
M V30 8 N 1.777565 -1.086515 0.000000 0
M V30 9 C 0.348623 -1.086515 0.000000 0
M V30 10 C -0.365848 -0.674015 0.000000 0
M V30 11 C -0.452084 0.146466 0.000000 0
M V30 12 C -1.259056 0.317993 0.000000 0
M V30 13 C -1.671556 -0.396478 0.000000 0
M V30 14 C -1.119523 -1.009572 0.000000 0
M V30 15 O -2.492036 -0.482714 0.000000 0
M V30 16 Cl 2.492036 1.800986 0.000000 0
M V30 17 O -0.063877 -1.800986 0.000000 0
M V30 18 C 0.761123 -1.800986 0.000000 0
M V30 END ATOM
M V30 BEGIN BOND
M V30 1 2 1 2
M V30 2 1 2 3
M V30 3 2 3 4
M V30 4 1 4 5
M V30 5 2 5 6
M V30 6 1 6 1
M V30 7 1 3 7
M V30 8 1 7 8 CFG=1
M V30 9 1 7 9
M V30 10 1 9 10
M V30 11 1 10 11
M V30 12 1 11 12
M V30 13 1 12 13
M V30 14 1 13 14
M V30 15 1 14 10
M V30 16 1 13 15 CFG=3
M V30 17 1 5 16
M V30 18 1 9 17 CFG=1
M V30 19 1 9 18 CFG=3
M V30 END BOND
M V30 BEGIN COLLECTION
M V30 MDLV30/STEABS ATOMS=(2 7 9)
M V30 MDLV30/STEREL1 ATOMS=(1 13)
M V30 END COLLECTION
M V30 END CTAB
M END
)CTAB"_ctab;
RGroupDecompositionParameters params;
params.matchingStrategy = GreedyChunks;
params.allowMultipleRGroupsOnUnlabelled = true;
params.onlyMatchAtRGroups = false;
RGroupDecomposition decomp(*core, params);
auto result = decomp.add(*mol1);
TEST_ASSERT(result == 0);
result = decomp.add(*mol2);
TEST_ASSERT(result == 1);
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 2);
TEST_ASSERT(rows[0].size() == 2);
TEST_ASSERT(rows[1].size() == 2);
auto core1 = rows[0]["Core"];
TEST_ASSERT(core1->getStereoGroups().size() == 1);
TEST_ASSERT(core1->getStereoGroups()[0].getGroupType() ==
StereoGroupType::STEREO_ABSOLUTE);
auto r1 = rows[0]["R1"];
TEST_ASSERT(r1->getStereoGroups().size() == 1);
TEST_ASSERT(r1->getStereoGroups()[0].getGroupType() ==
StereoGroupType::STEREO_ABSOLUTE);
auto core2 = rows[1]["Core"];
TEST_ASSERT(core2->getStereoGroups().size() == 1);
TEST_ASSERT(core2->getStereoGroups()[0].getGroupType() ==
StereoGroupType::STEREO_ABSOLUTE);
auto r2 = rows[1]["R1"];
TEST_ASSERT(r2->getStereoGroups().size() == 2);
TEST_ASSERT(r2->getStereoGroups()[0].getGroupType() ==
StereoGroupType::STEREO_ABSOLUTE);
TEST_ASSERT(r2->getStereoGroups()[1].getGroupType() ==
StereoGroupType::STEREO_OR);
}
void testEnumeratedCore() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "Test that enumerated cores behave properly"
<< std::endl;
auto core = R"CTAB(
Mrv2008 08242317002D
0 0 0 0 0 999 V3000
M V30 BEGIN CTAB
M V30 COUNTS 10 8 0 0 0
M V30 BEGIN ATOM
M V30 1 C -4.4167 11.04 0 0
M V30 2 C -5.7503 10.27 0 0
M V30 3 C -5.7503 8.6883 0 0
M V30 4 C -4.4167 7.9183 0 0
M V30 5 C -3.083 8.6883 0 0
M V30 6 C -3.083 10.2283 0 0
M V30 7 * -5.0835 10.655 0 0
M V30 8 F -5.0835 12.965 0 0
M V30 9 * -3.083 9.4583 0 0
M V30 10 Cl -1.928 11.4589 0 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 2 4 5
M V30 5 1 5 6
M V30 6 2 1 6
M V30 7 1 7 8 ENDPTS=(2 1 2) ATTACH=ANY
M V30 8 1 9 10 ENDPTS=(2 5 6) ATTACH=ANY
M V30 END BOND
M V30 END CTAB
M END
)CTAB"_ctab;
auto mol1 = "CC1=CC=C(F)C(Cl)=C1"_smiles;
auto mol2 = "CCC1=C(F)C=CC(Cl)=C1"_smiles;
RGroupDecompositionParameters params;
params.matchingStrategy = GreedyChunks;
params.allowMultipleRGroupsOnUnlabelled = true;
params.onlyMatchAtRGroups = false;
params.doEnumeration = true;
const char *expected[] = {"Core:Fc1ccc([*:2])cc1Cl R2:C[*:2]",
"Core:Fc1ccc(Cl)cc1[*:1] R1:CC[*:1]"};
RGroupDecomposition decomp(*core, params);
const auto add11 = decomp.add(*mol1);
TEST_ASSERT(add11 == 0);
const auto add12 = decomp.add(*mol2);
TEST_ASSERT(add12 == 1);
decomp.process();
auto rows = decomp.getRGroupsAsRows();
int i = 0;
for (RGroupRows::const_iterator it = rows.begin(); it != rows.end();
++it, ++i) {
TEST_ASSERT(i < 2);
CHECK_RGROUP(it, expected[i]);
}
}
void testTautomerCore() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "Test that cores handled as tautomers behave properly"
<< std::endl;
const auto core1 = "Oc1ccccn1"_smiles;
const auto core2 = "O=C1NC=CC=C1"_smiles;
const auto mol1 = "Cc1cnc(O)cc1Cl"_smiles;
const auto mol2 = "CC1=CNC(=O)C=C1F"_smiles;
RGroupDecompositionParameters params;
params.matchingStrategy = GreedyChunks;
params.allowMultipleRGroupsOnUnlabelled = true;
params.onlyMatchAtRGroups = false;
params.doTautomers = true;
const char *expected1[] = {
"Core:Oc1cc([*:2])c([*:1])cn1 R1:C[*:1] R2:Cl[*:2]",
"Core:O=c1cc([*:2])c([*:1])c[nH]1 R1:C[*:1] R2:F[*:2]"};
const char *expected2[] = {
"Core:Oc1cc([*:1])c([*:2])cn1 R1:Cl[*:1] R2:C[*:2]",
"Core:O=c1cc([*:1])c([*:2])c[nH]1 R1:F[*:1] R2:C[*:2]"};
RGroupDecomposition decomp1(*core1, params);
const auto add11 = decomp1.add(*mol1);
TEST_ASSERT(add11 == 0);
const auto add12 = decomp1.add(*mol2);
TEST_ASSERT(add12 == 1);
decomp1.process();
auto rows = decomp1.getRGroupsAsRows();
int i = 0;
for (RGroupRows::const_iterator it = rows.begin(); it != rows.end();
++it, ++i) {
TEST_ASSERT(i < 2);
CHECK_RGROUP(it, expected1[i]);
}
RGroupDecomposition decomp2(*core2, params);
const auto add21 = decomp2.add(*mol1);
TEST_ASSERT(add21 == 0);
const auto add22 = decomp2.add(*mol2);
TEST_ASSERT(add22 == 1);
decomp2.process();
rows = decomp2.getRGroupsAsRows();
i = 0;
for (RGroupRows::const_iterator it = rows.begin(); it != rows.end();
++it, ++i) {
TEST_ASSERT(i < 2);
CHECK_RGROUP(it, expected2[i]);
}
auto core3 = R"CTAB(
Mrv2008 08072313382D
9 9 0 0 0 0 999 V2000
5.9823 5.0875 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
5.9823 4.2625 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
5.2679 3.8500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
4.5534 4.2625 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
4.5534 5.0875 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
5.2679 5.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
5.2679 6.3250 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
6.6968 3.8500 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0
5.2679 3.0250 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0
1 2 2 0 0 0 0
2 3 1 0 0 0 0
3 4 2 0 0 0 0
4 5 1 0 0 0 0
5 6 1 0 0 0 0
6 7 2 0 0 0 0
1 6 1 0 0 0 0
2 8 1 0 0 0 0
3 9 1 0 0 0 0
M RGP 2 8 1 9 2
M END
)CTAB"_ctab;
auto smiles = MolToSmiles(*core3);
RGroupDecomposition decomp3(*core3, params);
const auto add31 = decomp3.add(*mol1);
TEST_ASSERT(add31 == 0);
const auto add32 = decomp3.add(*mol2);
TEST_ASSERT(add32 == 1);
decomp3.process();
rows = decomp3.getRGroupsAsRows();
i = 0;
for (RGroupRows::const_iterator it = rows.begin(); it != rows.end();
++it, ++i) {
TEST_ASSERT(i < 2);
CHECK_RGROUP(it, expected2[i]);
}
}
void testStereoBondBug() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog)
<< "Test that stereo bonds adjacent to the core or attachment atoms are handled correctly"
<< std::endl;
const auto core = R"CTAB(ACS Document 1996
ChemDraw10242316092D
6 6 0 0 0 0 0 0 0 0999 V2000
-0.7145 0.4125 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.7145 -0.4125 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.0000 -0.8250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.7145 -0.4125 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.7145 0.4125 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.0000 0.8250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1 2 2 0
2 3 1 0
3 4 2 0
4 5 1 0
5 6 2 0
6 1 1 0
M END
)CTAB"_ctab;
const auto mol = "C/C=C/C1=CC=CC=C1"_smiles;
RGroupDecompositionParameters params;
params.matchingStrategy = GreedyChunks;
params.allowMultipleRGroupsOnUnlabelled = true;
params.onlyMatchAtRGroups = false;
params.doEnumeration = false;
RGroupDecomposition decomp(*core, params);
const auto add1 = decomp.add(*mol);
TEST_ASSERT(add1 == 0);
decomp.process();
auto rows = decomp.getRGroupsAsRows();
auto r1 = rows[0]["R1"];
// Check to see that Stereo bond is present and defined
bool foundStereo = false;
for (const auto bond : r1->bonds()) {
if (bond->getStereo() > Bond::STEREOANY) {
TEST_ASSERT(!foundStereo);
foundStereo = true;
TEST_ASSERT(bond->getStereoAtoms().size() == 2);
}
}
TEST_ASSERT(foundStereo);
const auto core2 = R"CTAB(
ChemDraw10242316432D
7 7 0 0 0 0 0 0 0 0999 V2000
-1.0717 0.4125 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.0717 -0.4125 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.3572 -0.8250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.3572 -0.4125 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.3572 0.4125 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.3572 0.8250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1.0717 0.8250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1 2 2 0 0
2 3 1 0 0
3 4 2 0 0
4 5 1 0 0
5 6 2 0 0
6 1 1 0 0
5 7 1 0 0
M END
)CTAB"_ctab;
RGroupDecomposition decomp2(*core2, params);
const auto add2 = decomp2.add(*mol);
TEST_ASSERT(add2 == 0);
decomp2.process();
rows = decomp2.getRGroupsAsRows();
r1 = rows[0]["R1"];
// Check to see that Stereo bond is not present
foundStereo = false;
for (const auto bond : r1->bonds()) {
if (bond->getStereo() > Bond::STEREOANY) {
foundStereo = true;
}
}
TEST_ASSERT(!foundStereo);
const auto core3 = R"CTAB(
ChemDraw10252316142D
7 7 0 0 0 0 0 0 0 0999 V2000
-0.7145 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.7145 -0.8250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.0000 -1.2375 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.7145 -0.8250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.7145 0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
0.0000 0.4125 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.0000 1.2375 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1 2 2 0 0
2 3 1 0 0
3 4 1 0 0
4 5 2 0 0
5 6 1 0 0
6 1 1 0 0
6 7 2 0 0
M END
)CTAB"_ctab;
const auto mol3 = "C/C=C1N=CCC=C/1"_smiles;
RGroupDecomposition decomp3(*core3, params);
const auto add3 = decomp3.add(*mol3);
TEST_ASSERT(add3 == 0);
decomp3.process();
rows = decomp3.getRGroupsAsRows();
const auto c1 = rows[0]["Core"];
// Check to see that Stereo bond is not present
foundStereo = false;
for (const auto bond : c1->bonds()) {
if (bond->getStereo() > Bond::STEREOANY) {
TEST_ASSERT(!foundStereo);
foundStereo = true;
TEST_ASSERT(bond->getStereoAtoms().size() == 2);
}
}
TEST_ASSERT(foundStereo);
}
void testNotEnumeratedCore() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog)
<< "Test that enumerated setting for non enumerated cores behaves properly"
<< std::endl;
const auto core = "C1CCCCC1"_smarts;
const auto mol = "C1CCCCC1C"_smiles;
RGroupDecompositionParameters params;
params.matchingStrategy = GreedyChunks;
params.allowMultipleRGroupsOnUnlabelled = true;
params.onlyMatchAtRGroups = false;
params.doEnumeration = true;
params.doTautomers = false;
const char *expected = "Core:C1CCC([*:1])CC1 R1:C[*:1]";
RGroupDecomposition decomp(*core, params);
const auto add11 = decomp.add(*mol);
TEST_ASSERT(add11 == 0);
decomp.process();
auto rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1);
RGroupRows::const_iterator it = rows.begin();
CHECK_RGROUP(it, expected);
}
void testRgroupDecompZipping() {
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog)
<< "Test we can reconstruct rgroup decomps that break rings" << std::endl;
const auto core = "N1OCC1"_smiles;
const auto mol = "C1CC2ONC12"_smiles;
RGroupDecompositionParameters params;
params.matchingStrategy = GreedyChunks;
params.allowMultipleRGroupsOnUnlabelled = true;
params.onlyMatchAtRGroups = false;
params.doEnumeration = true;
params.doTautomers = false;
RGroupDecomposition decomp(*core, params);
const auto add11 = decomp.add(*mol);
TEST_ASSERT(add11 == 0);
decomp.process();
RGroupRows rows = decomp.getRGroupsAsRows();
TEST_ASSERT(rows.size() == 1);
RGroupRows::const_iterator it = rows.begin();
std::vector<ROMOL_SPTR> mols;
for (auto rgroups = it->begin(); rgroups != it->end(); ++rgroups) {
mols.push_back(rgroups->second);
}
auto res = molzip(mols);
TEST_ASSERT(MolToSmiles(*res) == "C1CC2ONC12")
for (RGroupRow &rgroup : rows) {
res = molzip(rgroup);
TEST_ASSERT(MolToSmiles(*res) == "C1CC2ONC12")
}
}
int main() {
RDLog::InitLogs();
boost::logging::disable_logs("rdApp.debug");
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
BOOST_LOG(rdInfoLog) << "Testing R-Group Decomposition \n";
#if 1
testSymmetryMatching(FingerprintVariance);
testSymmetryMatching();
testRGroupOnlyMatching();
testRingMatching();
testRingMatching3();
testMultiCore();
testGithub1550();
testRemoveHs();
testMatchOnlyAtRgroupHs();
testRingMatching2();
testGitHubIssue1705();
testGithub2332();
testSDFGRoupMultiCoreNoneShouldMatch();
testRowColumnAlignmentProblem();
testSymmetryIssues();
testMultipleCoreRelabellingIssues();
testGaSymmetryMatching(FingerprintVariance);
testGaSymmetryMatching(Match);
testGaBatch();
testUnprocessedMapping();
testSingleAtomBridge();
#endif
testSymmetryPerformance();
testScorePermutations();
testMultiCorePreLabelled();
testCoreWithRGroupAdjQuery();
testGeminalRGroups();
testMatchOnAnyAtom();
testNoAlignmentAndSymmetry();
testAddedRGroupsHaveCoords();
testUserMatchTypes();
testUnlabelledRGroupsOnAromaticNitrogen();
testAddHsDoesNotFail();
testNoTempLabels();
testNoSideChains();
testDoNotAddUnnecessaryRLabels();
testCoreWithAlsRecords();
testAlignOutputCoreToMolecule();
testWildcardInInput();
testDoNotChooseUnrelatedCores();
atomDegreePreconditionBug();
testGithub5222();
testGithub5569();
testGithub4505();
testMultipleGroupsToUnlabelledCoreAtomGithub5573();
testMultipleGroupsToUnlabelledCoreAtom();
testGitHub5631();
testGithub5613();
testRGroupCoordinatesAddedToCore();
testStereoGroupsPreserved();
testTautomerCore();
testEnumeratedCore();
testStereoBondBug();
testNotEnumeratedCore();
testRgroupDecompZipping();
BOOST_LOG(rdInfoLog)
<< "********************************************************\n";
return 0;
}
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