pub_soft/rdkit
3
0
Fork 0
mirror of https://github.com/rdkit/rdkit.git synced 2026-06-04 21:54:27 +08:00
Code Issues Packages Projects Releases Wiki Activity
Files
master
rdkit/Code/GraphMol/SynthonSpaceSearch/substructure_search_catch_tests.cpp
David Cosgrove 8ef091f306 Github9007 (#9022)
2025-12-29 21:08:10 +01:00

949 lines
30 KiB
C++
Raw Permalink Blame History

//
// Copyright (C) David Cosgrove 2024.
//
// @@ All Rights Reserved @@
// This file is part of the RDKit.
// The contents are covered by the terms of the BSD license
// which is included in the file license.txt, found at the root
// of the RDKit source tree.
#include <algorithm>
#include <chrono>
#include <cstdio>
#include <filesystem>
#include <fstream>
#include <GraphMol/Fingerprints/MorganGenerator.h>
#include <GraphMol/FileParsers/MolSupplier.h>
#include <GraphMol/GeneralizedSubstruct/XQMol.h>
#include <GraphMol/GenericGroups/GenericGroups.h>
#include <GraphMol/SubstructLibrary/SubstructLibrary.h>
#include <GraphMol/SynthonSpaceSearch/SearchResults.h>
#include <GraphMol/SynthonSpaceSearch/Synthon.h>
#include <GraphMol/SynthonSpaceSearch/SynthonSet.h>
#include <GraphMol/SynthonSpaceSearch/SynthonSpace.h>
#include <GraphMol/SynthonSpaceSearch/SynthonSpaceSearch_details.h>
#include <GraphMol/SmilesParse/SmilesParse.h>
#include <GraphMol/SmilesParse/SmartsWrite.h>
#include <GraphMol/SmilesParse/SmilesWrite.h>
#include <catch2/catch_all.hpp>
using namespace RDKit;
using namespace RDKit::SynthonSpaceSearch;
using namespace RDKit::SynthonSpaceSearch::details;
const char *rdbase = getenv("RDBASE");
std::unique_ptr<SubstructLibrary> loadSubstructLibrary(
const std::string &smiFile) {
std::unique_ptr<SubstructLibrary> subsLib(new SubstructLibrary());
v2::FileParsers::SmilesMolSupplierParams params;
params.titleLine = false;
v2::FileParsers::SmilesMolSupplier suppl(smiFile, params);
while (!suppl.atEnd()) {
subsLib->addMol(*suppl.next());
}
return subsLib;
}
std::map<std::string, std::string> loadLibrary(const std::string inFilename) {
v2::FileParsers::SmilesMolSupplierParams params;
params.titleLine = false;
v2::FileParsers::SmilesMolSupplier suppl(inFilename, params);
std::map<std::string, std::string> smiles;
while (!suppl.atEnd()) {
auto mol = suppl.next();
if (mol) {
smiles.insert(
std::make_pair(mol->getProp<std::string>(common_properties::_Name),
std::string(MolToSmiles(*mol))));
}
}
return smiles;
};
TEST_CASE("Test splits 1") {
const std::vector<std::string> smiles{"c1ccccc1CN1CCN(CC1)C(-O)c1ncc(F)cc1",
"CC(C)OCc1nnc(N2CC(C)CC2)n1C1CCCC1",
"c1ccccc1Oc1cccc2[nH]ccc12"};
std::vector<std::vector<size_t>> expCounts{
{1, 47, 1020, 0}, {1, 37, 562, 0}, {1, 29, 397, 0}};
for (size_t i = 0; i < smiles.size(); ++i) {
auto mol = v2::SmilesParse::MolFromSmiles(smiles[i]);
REQUIRE(mol);
bool timedOut = false;
auto fragments = splitMolecule(*mol, 3, 100000, nullptr, 1, timedOut);
CHECK(fragments.size() ==
std::accumulate(expCounts[i].begin(), expCounts[i].end(), size_t(0)));
// The first fragment set should just be the molecule itself. There
// shouldn't be any 4 fragment sets, but check.
for (size_t j = 0; j < 4; ++j) {
const auto numFragSets = std::accumulate(
fragments.begin(), fragments.end(), static_cast<size_t>(0),
[&](size_t prevRes,
const std::vector<std::unique_ptr<ROMol>> &frags) {
if (frags.size() == j + 1) {
return prevRes + 1;
}
return prevRes;
});
CHECK(numFragSets == expCounts[i][j]);
}
}
}
TEST_CASE("Enumerate") {
REQUIRE(rdbase);
std::string fName(rdbase);
// Making sure it works when the query has fewer bonds than maxBondSplits.
std::string libName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/triazole_space.txt";
SynthonSpace synthonspace;
bool cancelled = false;
synthonspace.readTextFile(libName, cancelled);
auto testName = std::tmpnam(nullptr);
BOOST_LOG(rdInfoLog) << "Enumerating to " << testName << std::endl;
synthonspace.writeEnumeratedFile(testName);
std::string enumLibName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/triazole_space_enum.smi";
auto newSmiles = loadLibrary(testName);
auto oldSmiles = loadLibrary(enumLibName);
REQUIRE(newSmiles.size() == oldSmiles.size());
for (const auto &[name, smiles] : oldSmiles) {
REQUIRE(oldSmiles.find(name) != oldSmiles.end());
REQUIRE(newSmiles.at(name) == oldSmiles.at(name));
}
std::remove(testName);
}
TEST_CASE("S Amide 1") {
REQUIRE(rdbase);
std::string fName(rdbase);
std::string libName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/amide_space.txt";
std::string enumLibName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/amide_space_enum.smi";
auto queryMol = "c1ccccc1C(=O)N1CCCC1"_smiles;
SynthonSpace synthonspace;
bool cancelled = false;
synthonspace.readTextFile(libName, cancelled);
SubstructMatchParameters matchParams;
SynthonSpaceSearchParams params;
auto results =
synthonspace.substructureSearch(*queryMol, matchParams, params);
CHECK(results.getHitMolecules().size() == 2);
std::set<std::string> resSmi;
for (const auto &r : results.getHitMolecules()) {
resSmi.insert(MolToSmiles(*r));
}
auto subsLib = loadSubstructLibrary(enumLibName);
auto query = "c1ccccc1C(=O)N1CCCC1"_smarts;
auto enumRes = subsLib->getMatches(*query);
std::set<std::string> enumSmi;
for (auto i : enumRes) {
enumSmi.insert(MolToSmiles(*subsLib->getMol(i)));
}
CHECK(resSmi == enumSmi);
resSmi.clear();
SearchResultCallback cb =
[&resSmi](const std::vector<std::unique_ptr<ROMol>> &r) {
for (auto &elem : r) {
resSmi.insert(MolToSmiles(*elem));
}
return false;
};
synthonspace.substructureSearch(*queryMol, cb, matchParams, params);
CHECK(resSmi == enumSmi);
}
TEST_CASE("Search Callback returns true") {
REQUIRE(rdbase);
std::string fName(rdbase);
std::string libName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/amide_space.txt";
std::string enumLibName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/amide_space_enum.smi";
auto queryMol = "c1ccccc1"_smiles;
SynthonSpace synthonspace;
bool cancelled = false;
synthonspace.readTextFile(libName, cancelled);
SubstructMatchParameters matchParams;
SynthonSpaceSearchParams params;
// set chunk size small so that we get multiple chunks back
params.toTryChunkSize = 2;
std::set<std::string> cbSmi;
bool retval = false;
SearchResultCallback cb =
[&cbSmi, &retval](const std::vector<std::unique_ptr<ROMol>> &r) {
for (auto &elem : r) {
CHECK(r.size() == 2);
cbSmi.insert(MolToSmiles(*elem));
}
return retval;
};
synthonspace.substructureSearch(*queryMol, cb, matchParams, params);
CHECK(cbSmi.size() == 6);
cbSmi.clear();
// return true from callback unconditionally, we receive only one chunk
retval = true;
synthonspace.substructureSearch(*queryMol, cb, matchParams, params);
CHECK(cbSmi.size() == 2);
}
TEST_CASE("S Urea 1") {
REQUIRE(rdbase);
std::string fName(rdbase);
std::string libName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/urea_space.txt";
SynthonSpace synthonspace;
bool cancelled = false;
synthonspace.readTextFile(libName, cancelled);
auto queryMol = "O=C(Nc1c(CNC=O)cc[s]1)c1nccnc1"_smiles;
auto results = synthonspace.substructureSearch(*queryMol);
CHECK(results.getHitMolecules().size() == 2);
}
TEST_CASE("S Simple query 1") {
REQUIRE(rdbase);
std::string fName(rdbase);
SynthonSpace synthonspace;
std::string libName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/idorsia_toy_space_a.spc";
synthonspace.readDBFile(libName);
{
// should give 220 hits for urea-3
auto queryMol = "c1ccccc1C(=O)N1CCCC1"_smiles;
auto results = synthonspace.substructureSearch(*queryMol);
CHECK(results.getHitMolecules().size() == 220);
CHECK(results.getMaxNumResults() == 220);
}
{
auto queryMol = "O=C(Nc1c(CNC=O)cc[s]1)c1nccnc1"_smiles;
auto results = synthonspace.substructureSearch(*queryMol);
CHECK(results.getHitMolecules().size() == 20);
}
{
// Test for multiple threads.
auto queryMol = "c1ccccc1C(=O)N1CCCC1"_smiles;
SynthonSpaceSearchParams params;
params.numThreads = -1;
SubstructMatchParameters matchParams;
auto results =
synthonspace.substructureSearch(*queryMol, matchParams, params);
CHECK(results.getHitMolecules().size() == 220);
CHECK(results.getMaxNumResults() == 220);
}
}
TEST_CASE("S Triazole") {
REQUIRE(rdbase);
std::string fName(rdbase);
std::string libName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/triazole_space.txt";
std::string enumLibName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/triazole_space_enum.smi";
SynthonSpace synthonspace;
bool cancelled = false;
synthonspace.readTextFile(libName, cancelled);
auto queryMol = "OCc1ncnn1"_smarts;
REQUIRE(queryMol);
auto results = synthonspace.substructureSearch(*queryMol);
CHECK(results.getHitMolecules().size() == 8);
std::set<std::string> resSmi;
for (const auto &r : results.getHitMolecules()) {
resSmi.insert(MolToSmiles(*r));
}
auto subsLib = loadSubstructLibrary(enumLibName);
auto enumRes = subsLib->getMatches(*queryMol);
std::set<std::string> enumSmi;
for (auto i : enumRes) {
enumSmi.insert(MolToSmiles(*subsLib->getMol(i)));
}
CHECK(resSmi == enumSmi);
}
TEST_CASE("S Quinoline") {
REQUIRE(rdbase);
std::string fName(rdbase);
std::string libName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/doebner_miller_space.txt";
std::string enumLibName =
fName +
"/Code/GraphMol/SynthonSpaceSearch/data/doebner_miller_space_enum.smi";
SynthonSpace synthonspace;
bool cancelled = false;
synthonspace.readTextFile(libName, cancelled);
{
auto queryMol = "c1ccccn1"_smiles;
auto results = synthonspace.substructureSearch(*queryMol);
CHECK(results.getHitMolecules().size() == 12);
std::set<std::string> resSmi;
for (const auto &r : results.getHitMolecules()) {
resSmi.insert(MolToSmiles(*r));
}
auto subsLib = loadSubstructLibrary(enumLibName);
auto enumRes = subsLib->getMatches(*queryMol);
std::set<std::string> enumSmi;
for (auto i : enumRes) {
enumSmi.insert(MolToSmiles(*subsLib->getMol(i)));
}
CHECK(resSmi == enumSmi);
}
}
TEST_CASE("S Substructure in 1 reagent") {
// Making sure it works when the query is a complete substructure of 1
// of the synthons in the library, so the whole library is a hit.
REQUIRE(rdbase);
std::string fName(rdbase);
std::string libName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/triazole_space.txt";
SynthonSpace synthonspace;
bool cancelled = false;
synthonspace.readTextFile(libName, cancelled);
{
auto queryMol = "N1CCCC1"_smiles;
auto results = synthonspace.substructureSearch(*queryMol);
CHECK(results.getHitMolecules().size() == 8);
}
{
auto queryMol = "N1CCC(C(F)(F)F)C1"_smiles;
auto results = synthonspace.substructureSearch(*queryMol);
CHECK(results.getHitMolecules().size() == 4);
}
{
auto queryMol = "C1CCCCC1"_smiles;
auto results = synthonspace.substructureSearch(*queryMol);
CHECK(results.getHitMolecules().empty());
}
}
TEST_CASE("Connector Regions") {
SECTION("Single tests") {
auto m1 = "[1*]CN(C[2*])Cc1ccccc1"_smiles;
REQUIRE(m1);
CHECK(MolToSmiles(*buildConnRegion(*m1)) == "[1*]CN(C)C[1*]");
auto m2 = "[1*]CN(C[2*])Cc1ccc(CN(C[3*])C[1*])cc1"_smiles;
REQUIRE(m2);
CHECK(MolToSmiles(*buildConnRegion(*m2)) ==
"[1*]CN(C)C[1*].[1*]CN(C)C[1*]");
auto m3 = "[2*]C"_smiles;
REQUIRE(m3);
CHECK(MolToSmiles(*buildConnRegion(*m3)) == "[1*]C");
auto m4 = "[1*]c1cnccc1"_smiles;
REQUIRE(m4);
CHECK(MolToSmiles(*buildConnRegion(*m4)) == "[1*]c(cc)cn");
}
SECTION("Built from file") {
REQUIRE(rdbase);
std::string fName(rdbase);
std::string libName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/urea_3.txt";
SynthonSpace synthonspace;
bool cancelled = false;
synthonspace.readTextFile(libName, cancelled);
const auto &rnames = synthonspace.getReactionNames();
const auto rs = synthonspace.getReaction(rnames.front());
CHECK(rs->getConnectorRegions().size() == 32);
}
}
TEST_CASE("DB Writer") {
REQUIRE(rdbase);
std::string fName(rdbase);
std::string libName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/doebner_miller_space.txt";
SynthonSpace synthonspace;
bool cancelled = false;
synthonspace.readTextFile(libName, cancelled);
CHECK(synthonspace.getNumReactions() == 1);
std::unique_ptr<FingerprintGenerator<std::uint64_t>> fpGen(
MorganFingerprint::getMorganGenerator<std::uint64_t>(2));
synthonspace.buildSynthonFingerprints(*fpGen);
auto spaceName = std::tmpnam(nullptr);
synthonspace.writeDBFile(spaceName);
SynthonSpace newsynthonspace;
newsynthonspace.readDBFile(spaceName);
std::shared_ptr<SynthonSet> irxn;
CHECK_NOTHROW(irxn = newsynthonspace.getReaction("doebner-miller-quinoline"));
const auto &orxn = synthonspace.getReaction("doebner-miller-quinoline");
CHECK(irxn->getId() == orxn->getId());
CHECK(irxn->getConnectorRegions().size() ==
orxn->getConnectorRegions().size());
CHECK(irxn->getConnRegFPs().size() == orxn->getConnRegFPs().size());
for (size_t i = 0; i < irxn->getConnRegFPs().size(); ++i) {
CHECK(*irxn->getConnRegFPs()[i] == *orxn->getConnRegFPs()[i]);
}
CHECK(irxn->getConnectors() == orxn->getConnectors());
CHECK(irxn->getSynthons().size() == orxn->getSynthons().size());
for (size_t i = 0; i < irxn->getSynthons().size(); ++i) {
CHECK(irxn->getSynthons()[i].size() == orxn->getSynthons()[i].size());
for (size_t j = 0; j < irxn->getSynthons().size(); ++j) {
CHECK(irxn->getSynthons()[i][j].first == orxn->getSynthons()[i][j].first);
CHECK(*irxn->getSynthons()[i][j].second->getFP() ==
*orxn->getSynthons()[i][j].second->getFP());
}
}
std::remove(spaceName);
// Check it behaves gracefully with a missing file
CHECK_THROWS(synthonspace.readDBFile(spaceName));
}
TEST_CASE("S Small query") {
REQUIRE(rdbase);
std::string fName(rdbase);
// Making sure it works when the query has fewer bonds than the maximum
// number of synthons.
std::string libName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/triazole_space.txt";
SynthonSpace synthonspace;
bool cancelled = false;
synthonspace.readTextFile(libName, cancelled);
auto queryMol = "C=CC"_smiles;
auto results = synthonspace.substructureSearch(*queryMol);
// The number of results is immaterial, it just matters that the search
// finished.
CHECK(results.getHitMolecules().empty());
}
TEST_CASE("S Map numbers in connectors") {
// Map numbers might occur in the connectors, e.g. [1*:1] as well
// as [1*]. This checks that that is the case.
REQUIRE(rdbase);
std::string fName(rdbase);
std::string libName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/map_numbers.txt";
SynthonSpace synthonspace;
bool cancelled = false;
synthonspace.readTextFile(libName, cancelled);
auto queryMol = "c1ccccc1C(=O)N1CCCC1"_smarts;
REQUIRE(queryMol);
auto results = synthonspace.substructureSearch(*queryMol);
// These were missing before map numbers were accommodated.
std::set<std::string> missNames{
"67468;30577;29389;a7", "67468;249279;29389;a7", "67468;24773;29389;a7",
"67468;29593;29389;a7", "67468;308698;29389;a7", "67468;56491;29389;a7",
"67468;265474;29389;a7", "67468;15535;29389;a7", "67468;44908;29389;a7",
"67468;59597;29389;a7", "67468;45686;29389;a7"};
std::set<std::string> hitNames;
for (const auto &hm : results.getHitMolecules()) {
hitNames.insert(hm->getProp<std::string>(common_properties::_Name));
}
CHECK(results.getHitMolecules().size() == 11);
CHECK(hitNames == missNames);
}
TEST_CASE("Greg Space Failure") {
// This failed at one point due to the aliphatic synthon, aromatic
// product issue.
REQUIRE(rdbase);
std::string fName(rdbase);
std::string libName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/gregs_space_fail.txt";
SynthonSpace synthonspace;
bool cancelled = false;
synthonspace.readTextFile(libName, cancelled);
auto queryMol =
"Cc1nn(C)c(C)c1-c1nc(Cn2cc(CNC(C)C(=O)NC3CCCC3)nn2)no1"_smarts;
REQUIRE(queryMol);
SubstructMatchParameters matchParams;
SynthonSpaceSearchParams params;
auto results =
synthonspace.substructureSearch(*queryMol, matchParams, params);
CHECK(results.getHitMolecules().size() == 1);
}
TEST_CASE("DOS File") {
REQUIRE(rdbase);
std::string fName(rdbase);
std::string libName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/amide_space_dos.txt";
SynthonSpace synthonspace;
bool cancelled = false;
synthonspace.readTextFile(libName, cancelled);
CHECK(synthonspace.getNumProducts() == 12);
}
TEST_CASE("Synthon Error") {
REQUIRE(rdbase);
std::string fName(rdbase);
{
std::string libName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/amide_space_error.txt";
SynthonSpace synthonspace;
bool cancelled = false;
CHECK_THROWS(synthonspace.readTextFile(libName, cancelled));
}
{
std::string libName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/synthon_error.txt";
SynthonSpace synthonspace;
bool cancelled = false;
CHECK_THROWS(synthonspace.readTextFile(libName, cancelled));
}
}
TEST_CASE("Amino Acid") {
// The issue here was that the SMARTS pattern should match just one synthon
// in the "library" but doesn't because the connector is on the nitrogen
// of the amino acid which says !$(N-[!#6;!#1]) i.e. the nitrogen can
// only be attached to a carbon or hydrogen, and in the synthon it's
// attached to a dummy atom.
REQUIRE(rdbase);
std::string fName(rdbase);
std::string libName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/amino_acid.txt";
SynthonSpace synthonspace;
bool cancelled = false;
synthonspace.readTextFile(libName, cancelled);
auto queryMol =
"[$(C-[C;!$(C=[!#6])]-[N;!H0;!$(N-[!#6;!#1]);!$(N-C=[O,N,S])])](=O)([O;H,-])"_smarts;
REQUIRE(queryMol);
SubstructMatchParameters matchParams;
SynthonSpaceSearchParams params;
auto results =
synthonspace.substructureSearch(*queryMol, matchParams, params);
CHECK(results.getHitMolecules().size() == 1);
}
TEST_CASE("Extended Query") {
REQUIRE(rdbase);
std::string fName(rdbase);
std::string libName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/extended_query.csv";
SynthonSpace synthonspace;
bool cancelled = false;
synthonspace.readTextFile(libName, cancelled);
{
auto queryMol =
v2::SmilesParse::MolFromSmarts("[#6]-*.c1nc2cccnc2n1 |m:1:3.10|");
REQUIRE(queryMol);
auto xrq = GeneralizedSubstruct::createExtendedQueryMol(*queryMol);
#ifdef RDK_USE_BOOST_SERIALIZATION
auto results = synthonspace.substructureSearch(xrq);
CHECK(results.getHitMolecules().size() == 12);
#else
CHECK_THROWS_AS(synthonspace.substructureSearch(xrq), Invar::Invariant);
#endif
MolOps::AdjustQueryParameters aqps;
aqps.adjustHeavyDegree = true;
aqps.adjustHeavyDegreeFlags =
MolOps::AdjustQueryWhichFlags::ADJUST_IGNORECHAINS;
auto xrq1 = GeneralizedSubstruct::createExtendedQueryMol(*queryMol, true,
true, true, aqps);
#ifdef RDK_USE_BOOST_SERIALIZATION
auto results1 = synthonspace.substructureSearch(xrq1);
CHECK(results1.getHitMolecules().size() == 5);
#else
CHECK_THROWS_AS(synthonspace.substructureSearch(xrq1), Invar::Invariant);
#endif
}
{
auto queryMol = R"CTAB(
Mrv2401 02062512582D
0 0 0 0 0 999 V3000
M V30 BEGIN CTAB
M V30 COUNTS 12 13 1 0 0
M V30 BEGIN ATOM
M V30 1 C -2.4167 7.8733 0 0
M V30 2 C -3.7503 7.1033 0 0
M V30 3 C -3.7503 5.5632 0 0
M V30 4 N -2.4167 4.7932 0 0
M V30 5 C -1.083 5.5632 0 0
M V30 6 C -1.083 7.1033 0 0
M V30 7 C 0.3973 7.5278 0 0
M V30 8 N 0.3104 5.0376 0 0
M V30 9 C 1.2585 6.251 0 0
M V30 10 C 2.7975 6.1973 0 0
M V30 11 N 3.6136 7.5032 0 0
M V30 12 * -2.4167 9.4133 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 6
M V30 8 1 5 8
M V30 9 1 8 9
M V30 10 2 7 9
M V30 11 1 9 10
M V30 12 1 10 11
M V30 13 1 1 12
M V30 END BOND
M V30 LINKNODE 1 3 2 10 9 10 11
M V30 BEGIN SGROUP
M V30 1 SUP 0 ATOMS=(1 12) SAP=(3 12 1 1) XBONDS=(1 13) LABEL=ARY ESTATE=E
M V30 END SGROUP
M V30 END CTAB
M END)CTAB"_ctab;
REQUIRE(queryMol);
GenericGroups::setGenericQueriesFromProperties(*queryMol);
auto xrq = GeneralizedSubstruct::createExtendedQueryMol(*queryMol);
#ifdef RDK_USE_BOOST_SERIALIZATION
auto results = synthonspace.substructureSearch(xrq);
CHECK(results.getHitMolecules().size() == 2);
#else
CHECK_THROWS_AS(synthonspace.substructureSearch(xrq), Invar::Invariant);
#endif
}
{
auto queryMol = R"CTAB(qry
Mrv2305 09052314502D
0 0 0 0 0 999 V3000
M V30 BEGIN CTAB
M V30 COUNTS 13 13 0 0 0
M V30 BEGIN ATOM
M V30 1 N -4.75 1.9567 0 0
M V30 2 C -6.0837 1.1867 0 0
M V30 3 C -6.0837 -0.3534 0 0
M V30 4 C -4.75 -1.1234 0 0
M V30 5 C -3.4163 -0.3534 0 0
M V30 6 C -3.4163 1.1867 0 0
M V30 7 N -1.9692 1.7134 0 0
M V30 8 N -1.8822 -0.7768 0 0
M V30 9 C -1.0211 0.4999 0 0
M V30 10 C 0.5179 0.5536 0 0
M V30 11 N 1.2409 1.9133 0 0
M V30 12 * -5.6391 -0.0967 0 0
M V30 13 C -5.6391 -2.4067 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 8 9
M V30 8 1 7 6
M V30 9 1 5 8
M V30 10 2 7 9
M V30 11 1 9 10
M V30 12 1 10 11
M V30 13 1 12 13 ENDPTS=(3 4 3 2) ATTACH=ANY
M V30 END BOND
M V30 LINKNODE 1 2 2 10 9 10 11
M V30 END CTAB
M END)CTAB"_ctab;
REQUIRE(queryMol);
GenericGroups::setGenericQueriesFromProperties(*queryMol);
auto xrq = GeneralizedSubstruct::createExtendedQueryMol(*queryMol);
#ifdef RDK_USE_BOOST_SERIALIZATION
auto results = synthonspace.substructureSearch(xrq);
CHECK(results.getHitMolecules().size() == 12);
#else
CHECK_THROWS_AS(synthonspace.substructureSearch(xrq), Invar::Invariant);
#endif
}
{
// Check maxHits is working correctly.
auto queryMol = v2::SmilesParse::MolFromSmarts(
"[#6]-1-[#6]-c2ccccc2-[#7]-1 |LN:1:1.2|");
REQUIRE(queryMol);
auto xrq = GeneralizedSubstruct::createExtendedQueryMol(*queryMol);
#ifdef RDK_USE_BOOST_SERIALIZATION
auto results = synthonspace.substructureSearch(xrq);
CHECK(results.getHitMolecules().size() == 8);
#else
CHECK_THROWS_AS(synthonspace.substructureSearch(xrq), Invar::Invariant);
#endif
SynthonSpaceSearch::SynthonSpaceSearchParams params;
params.maxHits = 5;
SubstructMatchParameters mparams;
#ifdef RDK_USE_BOOST_SERIALIZATION
auto results1 = synthonspace.substructureSearch(xrq, mparams, params);
CHECK(results1.getHitMolecules().size() == 5);
#else
CHECK_THROWS_AS(synthonspace.substructureSearch(xrq, mparams, params),
Invar::Invariant);
#endif
}
{
// Generic query check.
auto queryMol = R"CTAB(
Mrv2401 02062512582D
0 0 0 0 0 999 V3000
M V30 BEGIN CTAB
M V30 COUNTS 12 13 1 0 0
M V30 BEGIN ATOM
M V30 1 C -2.4167 7.8733 0 0
M V30 2 C -3.7503 7.1033 0 0
M V30 3 C -3.7503 5.5632 0 0
M V30 4 N -2.4167 4.7932 0 0
M V30 5 C -1.083 5.5632 0 0
M V30 6 C -1.083 7.1033 0 0
M V30 7 N 0.3973 7.5278 0 0
M V30 8 N 0.3104 5.0376 0 0
M V30 9 C 1.2585 6.251 0 0
M V30 10 C 2.7975 6.1973 0 0
M V30 11 N 3.6136 7.5032 0 0
M V30 12 * -2.4167 9.4133 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 6
M V30 8 1 5 8
M V30 9 1 8 9
M V30 10 2 7 9
M V30 11 1 9 10
M V30 12 1 10 11
M V30 13 1 1 12
M V30 END BOND
M V30 LINKNODE 1 3 2 10 9 10 11
M V30 BEGIN SGROUP
M V30 1 SUP 0 ATOMS=(1 12) SAP=(3 12 1 1) XBONDS=(1 13) LABEL=ARY ESTATE=E
M V30 END SGROUP
M V30 END CTAB
M END)CTAB"_ctab;
REQUIRE(queryMol);
GenericGroups::setGenericQueriesFromProperties(*queryMol);
auto xrq = GeneralizedSubstruct::createExtendedQueryMol(*queryMol);
SubstructMatchParameters mparams;
mparams.useGenericMatchers = true;
#ifdef RDK_USE_BOOST_SERIALIZATION
auto results1 = synthonspace.substructureSearch(xrq, mparams);
CHECK(results1.getHitMolecules().size() == 2);
#else
CHECK_THROWS_AS(synthonspace.substructureSearch(xrq, mparams),
Invar::Invariant);
#endif
}
}
TEST_CASE("Fails simple test (Github 8502)") {
SynthonSpace space;
std::istringstream iss(R"(SMILES synton_id synton# reaction_id
F[1*] 277310376-742385846 0 fake-chiral
Cl[1*] 287123986-010598048 0 fake-chiral
OC(N)([1*])[2*] 584456271-623025187 1 fake-chiral
OC(Br)([1*])[2*] 584456271-623025187 1 fake-chiral
F[2*] 277310376-742385dd 2 fake-chiral
)");
bool cancelled = false;
space.readStream(iss, cancelled);
auto mol1 = "C"_smiles;
REQUIRE(mol1);
auto res1 = space.substructureSearch(*mol1);
CHECK(res1.getHitMolecules().size() == 2);
auto mol2 = "CF"_smiles;
REQUIRE(mol2);
auto res2 = space.substructureSearch(*mol2);
CHECK(res2.getHitMolecules().size() == 2);
}
TEST_CASE("Chiral substructure search") {
SynthonSpace space;
std::istringstream iss(R"(SMILES synton_id synton# reaction_id
F[1*] 277310376-742385846 0 fake-chiral
Cl[1*] 287123986-010598048 0 fake-chiral
O[C@H](F)C(N)([1*])[2*] 584456271-623025187 1 fake-chiral
O[C@H](F)C(Br)([1*])[2*] 584456271-623025187 1 fake-chiral
F[2*] 277310376-742385dd 2 fake-chiral
)");
bool cancelled = false;
space.readStream(iss, cancelled);
auto qmol = "N-C-C"_smarts;
REQUIRE(qmol);
auto res1 = space.substructureSearch(*qmol);
CHECK(res1.getHitMolecules().size() == 2);
SubstructMatchParameters mparams;
SynthonSpaceSearchParams sparams;
sparams.minHitChiralAtoms = 2;
auto res2 = space.substructureSearch(*qmol, mparams, sparams);
REQUIRE(res2.getHitMolecules().size() == 1);
CHECK(MolToSmiles(*res2.getHitMolecules().front()) == "NC(F)(Cl)[C@H](O)F");
sparams.minHitChiralAtoms = 0;
sparams.maxHitChiralAtoms = 1;
auto res3 = space.substructureSearch(*qmol, mparams, sparams);
REQUIRE(res3.getHitMolecules().size() == 1);
CHECK(MolToSmiles(*res3.getHitMolecules().front()) == "NC(F)(F)[C@H](O)F");
sparams.maxHitChiralAtoms = 0;
auto res4 = space.substructureSearch(*qmol, mparams, sparams);
CHECK(res4.getHitMolecules().size() == 0);
}
TEST_CASE("Bad Chiral Atom Count") {
SynthonSpace space;
std::istringstream iss(
R"(SMILES synton_id synton# reaction_id release
C[U] 200011483129 1 4a 2024-09
c1c/c2n3/c1=C\C1=N/C(=C\c4c(C)c5c(n4[Mg]3)/C(=C3\N=C(\C=2)[C@@H](C)[C@@H]3C)[C@@H](C)C5=[U])C=C1 bad 2 4a 2024-09
)");
bool cancelled = false;
CHECK_NOTHROW(space.readStream(iss, cancelled));
}
TEST_CASE("Enhanced Stereochemistry - Github 8650") {
SynthonSpace space;
std::istringstream iss(
"SMILES\tsynton_id\tsynton#\treaction_id\trelease\nC[C@H]1CC[C@H](CC1)F |&1:1,4|\tABCDEFGHIJKL1234567890\t1\tx_1abc\t2024-02\n");
bool cancelled = false;
CHECK_NOTHROW(space.readStream(iss, cancelled));
// Bonus bug - it returned a valid reaction even if it had a different name.
CHECK_THROWS(space.getReaction("rhubarb"));
auto rxn = space.getReaction("x_1abc");
auto synthons = rxn->getSynthons();
REQUIRE(synthons.size() == 1);
REQUIRE(synthons[0].size() == 1);
CHECK(synthons[0][0].second->getSmiles() == "C[C@H]1CC[C@H](CC1)F |&1:1,4|");
}
TEST_CASE("Github 9009") {
{
// Single bond to "extra" aromatic C
SynthonSpace space;
std::istringstream iss(
R"(SMILES synton_id synton# reaction_id release
O=c1ccncn1[1*] 192 1 r2 1
[1*]c1ccccc1 227 2 r2 1
)");
bool cancelled = false;
space.readStream(iss, cancelled);
auto q1 = "O=c1n([c])cncc1"_smarts;
auto res1 = space.substructureSearch(*q1);
CHECK(res1.getHitMolecules().size() == 1);
auto q2 = "O=c1n([a])cncc1"_smarts;
auto res2 = space.substructureSearch(*q2);
CHECK(res2.getHitMolecules().size() == 1);
}
{
// Check that aromatic bond works
SynthonSpace space;
std::istringstream iss(
R"(SMILES synton_id synton# reaction_id release
[1*]C=CC=C[2*] 192 1 r2 1
O=C1NC=NC([2*])=C1[1*] 227 2 r2 1
)");
bool cancelled = false;
space.readStream(iss, cancelled);
auto q3 = "O=c1ncncc1c"_smarts;
auto res3 = space.substructureSearch(*q3);
CHECK(res3.getHitMolecules().size() == 1);
}
}
TEST_CASE("Github 9007") {
auto q1 = "O=c1ncnc([a])c1[a]"_smarts;
REQUIRE(q1);
auto q2 = "O=c1ncnc([c])c1[c]"_smarts;
REQUIRE(q2);
{
// Basic test. In the original bug, q1 gave hits, q2 didn't. q1 gave
// them for the wrong reason, though.
SynthonSpace space;
std::istringstream iss(
R"(SMILES synton_id synton# reaction_id release
[1*]c1nc[nH]c(=O)c1[2*] 1 1 r1 1
[1*]ccc(c[2*])[N+](=O)[O-] 10 2 r1 1
[2*]ncc(c[1*])[N+](=O)[O-] 11 2 r1 1
)");
bool cancelled = false;
space.readStream(iss, cancelled);
auto res1 = space.substructureSearch(*q1);
CHECK(res1.getHitMolecules().size() == 2);
auto res2 = space.substructureSearch(*q2);
CHECK(res2.getHitMolecules().size() == 1);
// Simpler case of just 1 dangling subsituent
auto q6 = "O=c1ncncc1c"_smarts;
REQUIRE(q6);
auto res6 = space.substructureSearch(*q6);
CHECK(res6.getHitMolecules().size() == 1);
auto q7 = "O=c1ncncc1a"_smarts;
REQUIRE(q7);
auto res7 = space.substructureSearch(*q7);
CHECK(res7.getHitMolecules().size() == 2);
}
{
// More complex case - 1 ring creation, extra substituent
SynthonSpace space;
std::istringstream iss(
R"(SMILES synton_id synton# reaction_id release
[1*]C1:C([2*])C(=O)N([3*])C=N1 192 1 r2 1
[1*]cc(C)cc([2*])Br 227 2 r2 1
[3*]c1c(Cl)ncnc1Cl 384 3 r2 1
)");
bool cancelled = false;
space.readStream(iss, cancelled);
auto res1 = space.substructureSearch(*q1);
CHECK(res1.getHitMolecules().size() == 1);
auto res2 = space.substructureSearch(*q2);
CHECK(res2.getHitMolecules().size() == 1);
auto q3 = "O=c1n(c)cnc(c)c1c"_smarts;
auto res3 = space.substructureSearch(*q3);
CHECK(res3.getHitMolecules().size() == 1);
}
{
// 2 ring creations.
SynthonSpace space;
std::istringstream iss(
R"(SMILES synton_id synton# reaction_id release
[1*]C1:C([2*])C(=O)N([3*])C([4*])=N1 1 1 r1 1
[1*]ccc(c[2*])[N+](=O)[O-] 10 2 r1 1
[3*]CCCC[4*] 100 3 r1 1
)");
bool cancelled = false;
space.readStream(iss, cancelled);
auto q4 = "O=c1n(C)c(C)nc(c)c(c)1"_smarts;
REQUIRE(q4);
auto res4 = space.substructureSearch(*q4);
CHECK(res4.getHitMolecules().size() == 1);
auto q5 = "O=c1n([A])c([A])nc([a])c([a])1"_smarts;
REQUIRE(q5);
auto res5 = space.substructureSearch(*q5);
CHECK(res5.getHitMolecules().size() == 1);
}
}
Reference in New Issue View Git Blame Copy Permalink