// // Copyright (C) 2021 Greg Landrum and other RDKit contributors // @@ All Rights Reserved @@ // This file is part of the RDKit. // The contents are covered by the terms of the BSD license // which is included in the file license.txt, found at the root // of the RDKit source tree. // #include #include "catch.hpp" #include #include #include #include #include #include #include #include #include "Embedder.h" #include "BoundsMatrixBuilder.h" #include using namespace RDKit; TEST_CASE("Torsions not found in fused macrocycles", "[macrocycles]") { RDLog::InitLogs(); SECTION("reported") { // this is 6VY8 from the PDB auto mol1 = "CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H](CCCC[NH3+])NC(=O)[C@H]([C@@H](C)O)NC(O)[C@@H]2CN3NNC[C@H]3C[C@H](NC1=O)C(O)N[C@@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CCCNC(N)=[NH2+])C(=O)N2"_smiles; REQUIRE(mol1); MolOps::addHs(*mol1); ForceFields::CrystalFF::CrystalFFDetails details; bool useExpTorsions = true; bool useSmallRingTorsions = false; bool useMacrocycleTorsions = true; bool useBasicKnowledge = true; unsigned int version = 2; bool verbose = true; std::stringstream sstrm; rdInfoLog->SetTee(sstrm); ForceFields::CrystalFF::getExperimentalTorsions( *mol1, details, useExpTorsions, useSmallRingTorsions, useMacrocycleTorsions, useBasicKnowledge, version, verbose); rdInfoLog->ClearTee(); auto txt = sstrm.str(); CHECK(txt.find("{9-}") != std::string::npos); } SECTION("edges") { std::vector> tests{ {"O=C1CNC(=O)C2CCC(N1)NC(=O)CNC2=O", true, 15}, // 9-9 {"O=C1NC2CCC(C(=O)N1)C(=O)NCC(=O)N2", true, 4}, // 9-8 {"O=C1NC2CCC(C(=O)N1)C(=O)NC(=O)N2", false, 0}, // 8-8 {"O=C1CC(=O)NC2NC(=O)CC(=O)NC(N1)NC(=O)CC(=O)N2", true, 18}}; // 12-12-12 for (const auto &tpl : tests) { std::unique_ptr m{SmilesToMol(std::get<0>(tpl))}; REQUIRE(m); MolOps::addHs(*m); ForceFields::CrystalFF::CrystalFFDetails details; bool useExpTorsions = true; bool useSmallRingTorsions = false; bool useMacrocycleTorsions = true; bool useBasicKnowledge = true; unsigned int version = 2; bool verbose = true; std::stringstream sstrm; rdInfoLog->SetTee(sstrm); std::cerr << "-----------" << std::endl; ForceFields::CrystalFF::getExperimentalTorsions( *m, details, useExpTorsions, useSmallRingTorsions, useMacrocycleTorsions, useBasicKnowledge, version, verbose); rdInfoLog->ClearTee(); auto txt = sstrm.str(); if (std::get<1>(tpl)) { CHECK(txt.find("{9-}") != std::string::npos); } else { CHECK(txt.find("{9-}") == std::string::npos); } CHECK(details.expTorsionAngles.size() == std::get<2>(tpl)); } } } namespace { void compareConfs(const ROMol *m, const ROMol *expected, int molConfId = -1, int expectedConfId = -1) { PRECONDITION(m, "bad pointer"); PRECONDITION(expected, "bad pointer"); TEST_ASSERT(m->getNumAtoms() == expected->getNumAtoms()); const Conformer &conf1 = m->getConformer(molConfId); const Conformer &conf2 = expected->getConformer(expectedConfId); for (unsigned int i = 0; i < m->getNumAtoms(); i++) { TEST_ASSERT(m->getAtomWithIdx(i)->getAtomicNum() == expected->getAtomWithIdx(i)->getAtomicNum()); RDGeom::Point3D pt1i = conf1.getAtomPos(i); RDGeom::Point3D pt2i = conf2.getAtomPos(i); TEST_ASSERT((pt1i - pt2i).length() < 0.05); } } } // namespace TEST_CASE("update parameters from JSON") { std::string rdbase = getenv("RDBASE"); SECTION("DG") { std::string fname = rdbase + "/Code/GraphMol/DistGeomHelpers/test_data/simple_torsion.dg.mol"; std::unique_ptr ref{MolFileToMol(fname, true, false)}; REQUIRE(ref); std::unique_ptr mol{SmilesToMol("OCCC")}; REQUIRE(mol); MolOps::addHs(*mol); CHECK(ref->getNumAtoms() == mol->getNumAtoms()); DGeomHelpers::EmbedParameters params; std::string json = R"JSON({"randomSeed":42})JSON"; DGeomHelpers::updateEmbedParametersFromJSON(params, json); CHECK(DGeomHelpers::EmbedMolecule(*mol, params) == 0); compareConfs(ref.get(), mol.get()); } SECTION("ETKDG") { std::string fname = rdbase + "/Code/GraphMol/DistGeomHelpers/test_data/simple_torsion.etkdg.mol"; std::unique_ptr ref{MolFileToMol(fname, true, false)}; REQUIRE(ref); std::unique_ptr mol{SmilesToMol("OCCC")}; REQUIRE(mol); MolOps::addHs(*mol); CHECK(ref->getNumAtoms() == mol->getNumAtoms()); DGeomHelpers::EmbedParameters params; std::string json = R"JSON({"randomSeed":42, "useExpTorsionAnglePrefs":true, "useBasicKnowledge":true})JSON"; DGeomHelpers::updateEmbedParametersFromJSON(params, json); CHECK(DGeomHelpers::EmbedMolecule(*mol, params) == 0); compareConfs(ref.get(), mol.get()); } SECTION("ETKDGv2") { std::string fname = rdbase + "/Code/GraphMol/DistGeomHelpers/test_data/torsion.etkdg.v2.mol"; std::unique_ptr ref{MolFileToMol(fname, true, false)}; REQUIRE(ref); std::unique_ptr mol{SmilesToMol("n1cccc(C)c1ON")}; REQUIRE(mol); MolOps::addHs(*mol); CHECK(ref->getNumAtoms() == mol->getNumAtoms()); DGeomHelpers::EmbedParameters params; std::string json = R"JSON({"randomSeed":42, "useExpTorsionAnglePrefs":true, "useBasicKnowledge":true, "ETversion":2})JSON"; DGeomHelpers::updateEmbedParametersFromJSON(params, json); CHECK(DGeomHelpers::EmbedMolecule(*mol, params) == 0); compareConfs(ref.get(), mol.get()); } SECTION("setting atommap") { std::unique_ptr mol{SmilesToMol("OCCC")}; REQUIRE(mol); MolOps::addHs(*mol); { DGeomHelpers::EmbedParameters params; std::string json = R"JSON({"randomSeed":42, "coordMap":{"0":[0,0,0],"1":[0,0,1.5],"2":[0,1.5,1.5]}})JSON"; DGeomHelpers::updateEmbedParametersFromJSON(params, json); CHECK(DGeomHelpers::EmbedMolecule(*mol, params) == 0); delete params.coordMap; auto conf = mol->getConformer(); auto v1 = conf.getAtomPos(0) - conf.getAtomPos(1); auto v2 = conf.getAtomPos(2) - conf.getAtomPos(1); CHECK(v1.angleTo(v2) == Approx(M_PI / 2).margin(0.15)); } } } TEST_CASE( "github #4346: Specified cis/trans stereo being ignored during " "conformation generation in macrocycles") { SECTION("basics 1") { auto m1 = "C1C/C=C/CCCCCCCC1"_smiles; REQUIRE(m1); CHECK(m1->getBondBetweenAtoms(2, 3)->getStereo() == Bond::BondStereo::STEREOE); MolOps::addHs(*m1); DGeomHelpers::EmbedParameters params = DGeomHelpers::KDG; params.randomSeed = 0xf00d; CHECK(DGeomHelpers::EmbedMolecule(*m1, params) != -1); MolOps::assignStereochemistryFrom3D(*m1); CHECK(m1->getBondBetweenAtoms(2, 3)->getStereo() == Bond::BondStereo::STEREOE); } SECTION("basics 2") { auto m1 = "C1C/C=C\\CCCCCCCC1"_smiles; REQUIRE(m1); CHECK(m1->getBondBetweenAtoms(2, 3)->getStereo() == Bond::BondStereo::STEREOZ); MolOps::addHs(*m1); DGeomHelpers::EmbedParameters params = DGeomHelpers::KDG; params.randomSeed = 0xf00d; CHECK(DGeomHelpers::EmbedMolecule(*m1, params) != -1); MolOps::assignStereochemistryFrom3D(*m1); CHECK(m1->getBondBetweenAtoms(2, 3)->getStereo() == Bond::BondStereo::STEREOZ); } } TEST_CASE("nontetrahedral stereo", "[nontetrahedral]") { SECTION("bounds matrix basics") { { auto m = "Cl[Pt@SP1]([35Cl])([36Cl])[37Cl]"_smiles; REQUIRE(m); CHECK(Chirality::getChiralAcrossAtom(m->getAtomWithIdx(1), m->getAtomWithIdx(0)) ->getIdx() == 3); CHECK(Chirality::getChiralAcrossAtom(m->getAtomWithIdx(1), m->getAtomWithIdx(2)) ->getIdx() == 4); CHECK_THAT( Chirality::getIdealAngleBetweenLigands( m->getAtomWithIdx(1), m->getAtomWithIdx(0), m->getAtomWithIdx(3)), Catch::Matchers::WithinAbs(180, 0.001)); CHECK_THAT( Chirality::getIdealAngleBetweenLigands( m->getAtomWithIdx(1), m->getAtomWithIdx(0), m->getAtomWithIdx(2)), Catch::Matchers::WithinAbs(90, 0.001)); DistGeom::BoundsMatPtr bm{new DistGeom::BoundsMatrix(m->getNumAtoms())}; DGeomHelpers::initBoundsMat(bm, 0.0, 1000.0); DGeomHelpers::setTopolBounds(*m, bm); // std::cerr << *bm << std::endl; CHECK(bm->getLowerBound(0, 3) - bm->getLowerBound(0, 2) > 1.0); CHECK(bm->getUpperBound(0, 3) - bm->getUpperBound(0, 2) > 1.0); } { auto m = "Cl[Pt@SP1]([35Cl])[36Cl]"_smiles; REQUIRE(m); CHECK(Chirality::getChiralAcrossAtom(m->getAtomWithIdx(1), m->getAtomWithIdx(0)) ->getIdx() == 3); CHECK(!Chirality::getChiralAcrossAtom(m->getAtomWithIdx(1), m->getAtomWithIdx(2))); CHECK_THAT( Chirality::getIdealAngleBetweenLigands( m->getAtomWithIdx(1), m->getAtomWithIdx(0), m->getAtomWithIdx(3)), Catch::Matchers::WithinAbs(180, 0.001)); CHECK_THAT( Chirality::getIdealAngleBetweenLigands( m->getAtomWithIdx(1), m->getAtomWithIdx(0), m->getAtomWithIdx(2)), Catch::Matchers::WithinAbs(90, 0.001)); DistGeom::BoundsMatPtr bm{new DistGeom::BoundsMatrix(m->getNumAtoms())}; DGeomHelpers::initBoundsMat(bm, 0.0, 1000.0); DGeomHelpers::setTopolBounds(*m, bm); // std::cerr << *bm << std::endl; CHECK(bm->getLowerBound(0, 3) - bm->getLowerBound(0, 2) > 1.0); CHECK(bm->getUpperBound(0, 3) - bm->getUpperBound(0, 2) > 1.0); } { // note that things aren't quite as nice here since we don't actually have // TBP UFF parameters auto m = "Cl[Pt@TB1]([35Cl])([36Cl])([37Cl])[38Cl]"_smiles; REQUIRE(m); CHECK(Chirality::getChiralAcrossAtom(m->getAtomWithIdx(1), m->getAtomWithIdx(0)) ->getIdx() == 5); CHECK(!Chirality::getChiralAcrossAtom(m->getAtomWithIdx(1), m->getAtomWithIdx(2))); CHECK_THAT( Chirality::getIdealAngleBetweenLigands( m->getAtomWithIdx(1), m->getAtomWithIdx(0), m->getAtomWithIdx(5)), Catch::Matchers::WithinAbs(180, 0.001)); CHECK_THAT( Chirality::getIdealAngleBetweenLigands( m->getAtomWithIdx(1), m->getAtomWithIdx(0), m->getAtomWithIdx(2)), Catch::Matchers::WithinAbs(90, 0.001)); CHECK_THAT( Chirality::getIdealAngleBetweenLigands( m->getAtomWithIdx(1), m->getAtomWithIdx(3), m->getAtomWithIdx(2)), Catch::Matchers::WithinAbs(120, 0.001)); DistGeom::BoundsMatPtr bm{new DistGeom::BoundsMatrix(m->getNumAtoms())}; DGeomHelpers::initBoundsMat(bm, 0.0, 1000.0); DGeomHelpers::setTopolBounds(*m, bm); CHECK(bm->getLowerBound(0, 5) - bm->getLowerBound(0, 2) > 0.5); CHECK(bm->getUpperBound(0, 5) - bm->getUpperBound(0, 2) > 0.5); CHECK(bm->getLowerBound(0, 5) - bm->getLowerBound(2, 3) > 0.5); CHECK(bm->getUpperBound(0, 5) - bm->getUpperBound(2, 3) > 0.5); CHECK(bm->getLowerBound(2, 3) - bm->getLowerBound(0, 2) > 0.5); CHECK(bm->getUpperBound(2, 3) - bm->getUpperBound(0, 2) > 0.5); } { auto m = "Cl[Th@OH1]([35Cl])([36Cl])([37Cl])([38Cl])[39Cl]"_smiles; REQUIRE(m); CHECK(Chirality::getChiralAcrossAtom(m->getAtomWithIdx(1), m->getAtomWithIdx(0)) ->getIdx() == 6); CHECK(Chirality::getChiralAcrossAtom(m->getAtomWithIdx(1), m->getAtomWithIdx(2)) ->getIdx() == 4); CHECK(Chirality::getChiralAcrossAtom(m->getAtomWithIdx(1), m->getAtomWithIdx(3)) ->getIdx() == 5); CHECK_THAT( Chirality::getIdealAngleBetweenLigands( m->getAtomWithIdx(1), m->getAtomWithIdx(0), m->getAtomWithIdx(6)), Catch::Matchers::WithinAbs(180, 0.001)); CHECK_THAT( Chirality::getIdealAngleBetweenLigands( m->getAtomWithIdx(1), m->getAtomWithIdx(0), m->getAtomWithIdx(2)), Catch::Matchers::WithinAbs(90, 0.001)); CHECK_THAT( Chirality::getIdealAngleBetweenLigands( m->getAtomWithIdx(1), m->getAtomWithIdx(4), m->getAtomWithIdx(2)), Catch::Matchers::WithinAbs(180, 0.001)); CHECK_THAT( Chirality::getIdealAngleBetweenLigands( m->getAtomWithIdx(1), m->getAtomWithIdx(3), m->getAtomWithIdx(2)), Catch::Matchers::WithinAbs(90, 0.001)); DistGeom::BoundsMatPtr bm{new DistGeom::BoundsMatrix(m->getNumAtoms())}; DGeomHelpers::initBoundsMat(bm, 0.0, 1000.0); DGeomHelpers::setTopolBounds(*m, bm); CHECK(bm->getLowerBound(0, 6) - bm->getLowerBound(0, 2) > 0.5); CHECK(bm->getUpperBound(0, 6) - bm->getUpperBound(0, 3) > 0.5); CHECK(bm->getLowerBound(0, 6) - bm->getLowerBound(2, 3) > 0.5); CHECK(bm->getUpperBound(0, 6) - bm->getUpperBound(2, 4) < 0.01); CHECK(bm->getLowerBound(2, 4) - bm->getLowerBound(2, 3) > 0.5); } } #if 1 SECTION("Embedding") { { auto m = "Cl[Pt@SP1](<-N)(<-N)[Cl]"_smiles; REQUIRE(m); m->setProp("_Name", "cis platin"); MolOps::addHs(*m); CHECK(DGeomHelpers::EmbedMolecule(*m) == 0); auto mb = MolToV3KMolBlock(*m); // std::cerr << mb << std::endl; std::unique_ptr m2(MolBlockToMol(mb)); MolOps::assignStereochemistryFrom3D(*m2); CHECK(m2->getAtomWithIdx(1)->getChiralTag() == Atom::ChiralType::CHI_SQUAREPLANAR); unsigned int perm = 100; CHECK(m2->getAtomWithIdx(1)->getPropIfPresent( common_properties::_chiralPermutation, perm)); CHECK(perm == 1); } { auto m = "Cl[Pt@SP3](<-N)(<-N)[Cl]"_smiles; REQUIRE(m); m->setProp("_Name", "trans platin"); MolOps::addHs(*m); CHECK(DGeomHelpers::EmbedMolecule(*m) == 0); auto mb = MolToV3KMolBlock(*m); // std::cerr << mb << std::endl; std::unique_ptr m2(MolBlockToMol(mb)); MolOps::assignStereochemistryFrom3D(*m2); CHECK(m2->getAtomWithIdx(1)->getChiralTag() == Atom::ChiralType::CHI_SQUAREPLANAR); unsigned int perm = 100; CHECK(m2->getAtomWithIdx(1)->getPropIfPresent( common_properties::_chiralPermutation, perm)); CHECK(perm == 3); } } #endif } TEST_CASE("problems with bounds matrix smoothing and aromatic sulfur") { SECTION("basics") { auto core = R"CTAB(test structure - renumbered RDKit 3D 7 7 0 0 0 0 0 0 0 0999 V2000 48.6842 -14.8137 0.1450 C 0 0 0 0 0 0 0 0 0 0 0 0 48.0829 -13.5569 0.6868 C 0 0 0 0 0 0 0 0 0 0 0 0 48.0162 -12.0909 -0.1327 S 0 0 0 0 0 0 0 0 0 0 0 0 47.1565 -11.3203 1.0899 C 0 0 0 0 0 0 0 0 0 0 0 0 46.9350 -12.2470 2.1088 C 0 0 0 0 0 0 0 0 0 0 0 0 46.1942 -11.9293 3.3432 C 0 0 0 0 0 0 0 0 0 0 0 0 47.4440 -13.4879 1.8745 N 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 7 2 0 2 3 1 0 7 5 1 0 5 4 2 0 5 6 1 0 4 3 1 0 M END)CTAB"_ctab; REQUIRE(core); auto thiaz = "Cc1scc(C)n1"_smiles; REQUIRE(thiaz); MolOps::addHs(*thiaz); DGeomHelpers::EmbedParameters ps = DGeomHelpers::ETKDGv3; const auto conf = core->getConformer(); std::map cmap; for (unsigned i = 0; i < core->getNumAtoms(); ++i) { cmap[i] = conf.getAtomPos(i); } ps.coordMap = &cmap; ps.randomSeed = 0xf00d; auto cid = DGeomHelpers::EmbedMolecule(*thiaz, ps); CHECK(cid >= 0); } SECTION("bulk") { // run a bunch of molecules with S-containing aromatic heterocycles std::vector smileses = { "[O-][S+](c1ccccn1)c1cncs1", "Cn1cccc1C(=O)Nc1nccs1", "Cc1csc(=N)n1-c1ccc(Cl)cc1", "Nc1ncc([S+]([O-])c2ncccn2)s1", "CCCN1CCC=C(c2csc(N)n2)C1", "CNc1ncc([S+]([O-])c2ccccn2)s1", "Cn1nnnc1SCc1nc2ccccc2s1", "CCCC(C(=O)Nc1nccs1)c1ccccc1", "Cc1ccc(NC(=O)c2sc(Cl)nc2C)c(C)c1", "CCc1nc(-c2ccc(Cl)cc2)sc1C(=O)OC", "Cc1nc(CNS(=O)(=O)c2ccc(Cl)cc2)cs1", "Cc1ccc2sc(C)[n+](CCC(C)S(=O)(=O)[O-])c2c1", "Nc1nc2c(s1)-c1ccccc1Sc1ccccc1-2", "COc1ccccc1OCC(=O)Nc1nc(C)c(C)s1", "COc1ccc(NC(=O)Nc2sc(=S)n(C)c2C)cc1", "C=CCNc1nc(-c2c[nH]c3c(CC)cccc23)cs1", }; auto patt = "[s]1*c[!#6]c1"_smarts; REQUIRE(patt); for (const auto &smi : smileses) { INFO(smi); std::unique_ptr mol{SmilesToMol(smi)}; REQUIRE(mol); MolOps::addHs(*mol); DGeomHelpers::EmbedParameters ps = DGeomHelpers::ETKDGv3; ps.randomSeed = 0xf00d; auto cid = DGeomHelpers::EmbedMolecule(*mol, ps); REQUIRE(cid >= 0); UFF::UFFOptimizeMolecule(*mol); auto match = SubstructMatch(*mol, *patt); REQUIRE(match.size() >= 1); const auto conf = mol->getConformer(); std::map cmap; for (auto &mi : match[0]) { cmap[mi.second] = conf.getAtomPos(mi.second); } ps.coordMap = &cmap; auto cid2 = DGeomHelpers::EmbedMolecule(*mol, ps); CHECK(cid2 >= 0); } } SECTION("phosphorous") { std::vector smileses = { "CCOC(=O)c1pc(P(Cl)Cl)c2n1[C@@H](C)C(=O)Nc1ccc(C)cc1-2", "N(c1c(O)ccc2c(P(Cl)Cl)pc(C(=O)O)n12)[N+](=O)[O-]", }; auto patt = "[p]1*c[!#6]c1"_smarts; REQUIRE(patt); for (const auto &smi : smileses) { INFO(smi); std::unique_ptr mol{SmilesToMol(smi)}; REQUIRE(mol); MolOps::addHs(*mol); DGeomHelpers::EmbedParameters ps = DGeomHelpers::ETKDGv3; ps.randomSeed = 0xf00d; auto cid = DGeomHelpers::EmbedMolecule(*mol, ps); REQUIRE(cid >= 0); UFF::UFFOptimizeMolecule(*mol); auto match = SubstructMatch(*mol, *patt); REQUIRE(match.size() >= 1); const auto conf = mol->getConformer(); std::map cmap; for (auto &mi : match[0]) { cmap[mi.second] = conf.getAtomPos(mi.second); } ps.coordMap = &cmap; auto cid2 = DGeomHelpers::EmbedMolecule(*mol, ps); CHECK(cid2 >= 0); } } } TEST_CASE("double bond stereo not honored in conformer generator") { SECTION("mol 1 basics") { // this test used to fail // from the platinum set auto m = "O=C1OCC/C=C/CC/C=C/C(=N/OCC(=O)N2CCCCC2)Cc2cc(O)cc(O)c21"_smiles; REQUIRE(m); RWMol cp(*m); MolOps::addHs(cp); DGeomHelpers::EmbedParameters ps = DGeomHelpers::ETKDGv3; ps.randomSeed = 0xf00d + 81; auto cid = DGeomHelpers::EmbedMolecule(cp, ps); REQUIRE(cid >= 0); MolOps::assignStereochemistryFrom3D(cp); // std::cerr << MolToMolBlock(cp) << std::endl; for (const auto bnd : cp.bonds()) { if (bnd->getBondType() == Bond::BondType::DOUBLE) { INFO(bnd->getIdx()); CHECK(bnd->getStereo() == m->getBondWithIdx(bnd->getIdx())->getStereo()); } } } SECTION("mol 1 multiple loops") { // from the platinum set auto m = "O=C1OCC/C=C/CC/C=C/C(=N/OCC(=O)N2CCCCC2)Cc2cc(O)cc(O)c21"_smiles; REQUIRE(m); RWMol cp(*m); MolOps::addHs(cp); DGeomHelpers::EmbedParameters ps = DGeomHelpers::ETKDGv3; for (unsigned int iter = 0; iter < 10; ++iter) { RWMol lcp(cp); ps.randomSeed = 0xf00d + iter; auto cid = DGeomHelpers::EmbedMolecule(lcp, ps); REQUIRE(cid >= 0); MolOps::assignStereochemistryFrom3D(lcp); // std::cerr << MolToMolBlock(cp) << std::endl; for (const auto bnd : lcp.bonds()) { if (bnd->getBondType() == Bond::BondType::DOUBLE) { INFO(iter); CHECK(bnd->getStereo() == m->getBondWithIdx(bnd->getIdx())->getStereo()); } } } } SECTION("github #5913") { auto m = "[H]/C(F)=C([H])\\C([H])=C(/[H])Br"_smiles; REQUIRE(m); RWMol cp(*m); MolOps::addHs(cp); DGeomHelpers::EmbedParameters ps = DGeomHelpers::ETKDGv3; for (unsigned int iter = 0; iter < 50; ++iter) { RWMol lcp(cp); ps.randomSeed = 0 + iter; auto cid = DGeomHelpers::EmbedMolecule(lcp, ps); REQUIRE(cid >= 0); MolOps::assignStereochemistryFrom3D(lcp); // std::cerr << MolToMolBlock(cp) << std::endl; for (const auto bnd : lcp.bonds()) { if (bnd->getBondType() == Bond::BondType::DOUBLE) { INFO(iter); CHECK(bnd->getStereo() == m->getBondWithIdx(bnd->getIdx())->getStereo()); } } } } SECTION("github #5283") { auto oVal = Chirality::getUseLegacyStereoPerception(); Chirality::setUseLegacyStereoPerception(false); auto m = "Cc3nn(CC(=O)N2CCN(c1ccccc1)CC2)c(C)c3/N=N\\c6ccc(CNC(=O)CCC(=O)Nc4cccc5C(=O)NCc45)cc6"_smiles; REQUIRE(m); RWMol cp(*m); MolOps::addHs(cp); DGeomHelpers::EmbedParameters ps = DGeomHelpers::ETKDGv3; ps.enforceChirality = false; for (unsigned int iter = 0; iter < 10; ++iter) { INFO(iter); RWMol lcp(cp); ps.randomSeed = 140 + iter; auto cid = DGeomHelpers::EmbedMolecule(lcp, ps); REQUIRE(cid >= 0); MolOps::assignStereochemistryFrom3D(lcp, cid, true); auto bnd = lcp.getBondBetweenAtoms(22, 23); REQUIRE(bnd); REQUIRE(bnd->getBondType() == Bond::BondType::DOUBLE); CHECK(bnd->getStereo() == m->getBondWithIdx(bnd->getIdx())->getStereo()); } Chirality::setUseLegacyStereoPerception(oVal); } } TEST_CASE("tracking failure causes"){SECTION("basics"){ auto mol = "C=CC1=C(N)Oc2cc1c(-c1cc(C(C)O)cc(=O)cc1C1NCC(=O)N1)c(OC)c2OC"_smiles; REQUIRE(mol); MolOps::addHs(*mol); DGeomHelpers::EmbedParameters ps = DGeomHelpers::ETKDGv3; ps.randomSeed = 0xf00d; ps.trackFailures = true; ps.maxIterations = 50; ps.randomSeed = 42; auto cid = DGeomHelpers::EmbedMolecule(*mol, ps); CHECK(cid < 0); CHECK(ps.failures[DGeomHelpers::EmbedFailureCauses::INITIAL_COORDS] > 5); CHECK(ps.failures[DGeomHelpers::EmbedFailureCauses::ETK_MINIMIZATION] > 10); auto fail_cp = ps.failures; // make sure we reset the counts each time cid = DGeomHelpers::EmbedMolecule(*mol, ps); CHECK(ps.failures == fail_cp); } SECTION("chirality") { auto mol = R"CTAB( Ketcher 1102315302D 1 1.00000 0.00000 0 10 11 0 0 1 0 0 0 0 0999 V2000 10.1340 -11.0250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.1340 -12.0250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 11.0000 -12.5250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 11.8660 -12.0250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 11.8660 -11.0250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 11.0000 -10.5250 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 11.0000 -11.5250 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 11.2588 -12.4909 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2680 -10.5250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 12.7629 -12.4673 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1 6 1 0 0 0 1 2 1 0 0 0 2 3 1 0 0 0 3 4 1 0 0 0 4 5 1 0 0 0 5 6 1 0 0 0 1 7 1 0 0 0 7 8 1 0 0 0 8 4 1 0 0 0 1 9 1 1 0 0 4 10 1 1 0 0 M END )CTAB"_ctab; REQUIRE(mol); MolOps::addHs(*mol); DGeomHelpers::EmbedParameters ps = DGeomHelpers::ETKDGv3; ps.randomSeed = 0xf00d; ps.trackFailures = true; ps.maxIterations = 50; auto cid = DGeomHelpers::EmbedMolecule(*mol, ps); CHECK(cid < 0); CHECK(ps.failures[DGeomHelpers::EmbedFailureCauses::INITIAL_COORDS] > 5); CHECK(ps.failures[DGeomHelpers::EmbedFailureCauses::FINAL_CHIRAL_BOUNDS] > 5); } #ifdef RDK_TEST_MULTITHREADED SECTION("multithreaded") { auto mol = "C=CC1=C(N)Oc2cc1c(-c1cc(C(C)O)cc(=O)cc1C1NCC(=O)N1)c(OC)c2OC"_smiles; REQUIRE(mol); MolOps::addHs(*mol); DGeomHelpers::EmbedParameters ps = DGeomHelpers::ETKDGv3; ps.randomSeed = 0xf00d; ps.trackFailures = true; ps.maxIterations = 10; ps.randomSeed = 42; auto cids = DGeomHelpers::EmbedMultipleConfs(*mol, 20, ps); DGeomHelpers::EmbedParameters ps2 = ps; ps2.numThreads = 4; auto cids2 = DGeomHelpers::EmbedMultipleConfs(*mol, 20, ps2); CHECK(cids2 == cids); CHECK(ps.failures == ps2.failures); } #endif } TEST_CASE("Github #5883: confgen failing for chiral N in a three ring") { SECTION("basics1") { auto mol = "N1[C@H-]C1"_smiles; REQUIRE(mol); MolOps::addHs(*mol); mol->getAtomWithIdx(1)->setChiralTag(Atom::ChiralType::CHI_TETRAHEDRAL_CCW); DGeomHelpers::EmbedParameters ps = DGeomHelpers::ETKDGv3; ps.randomSeed = 42; ps.maxIterations = 1; auto cid = DGeomHelpers::EmbedMolecule(*mol, ps); CHECK(cid >= 0); } SECTION("basics2") { auto mol = "N1[N@H]C1"_smiles; REQUIRE(mol); MolOps::addHs(*mol); mol->getAtomWithIdx(1)->setChiralTag(Atom::ChiralType::CHI_TETRAHEDRAL_CCW); DGeomHelpers::EmbedParameters ps = DGeomHelpers::ETKDGv3; ps.randomSeed = 42; ps.maxIterations = 1; auto cid = DGeomHelpers::EmbedMolecule(*mol, ps); CHECK(cid >= 0); } SECTION("no ring") { auto mol = "N[C@H-]C"_smiles; REQUIRE(mol); MolOps::addHs(*mol); mol->getAtomWithIdx(1)->setChiralTag(Atom::ChiralType::CHI_TETRAHEDRAL_CCW); DGeomHelpers::EmbedParameters ps = DGeomHelpers::ETKDGv3; ps.randomSeed = 42; ps.maxIterations = 1; auto cid = DGeomHelpers::EmbedMolecule(*mol, ps); CHECK(cid >= 0); } } TEST_CASE("Github #6365: cannot generate conformers for PF6- or SF6") { SECTION("basics") { std::vector smileses = {"S(F)(F)(F)(F)(F)F", "[P-](F)(F)(F)(F)(F)F"}; for (const auto &smi : smileses) { std::unique_ptr mol{SmilesToMol(smi)}; REQUIRE(mol); DGeomHelpers::EmbedParameters ps = DGeomHelpers::ETKDGv3; ps.randomSeed = 42; ps.useRandomCoords = true; auto cid = DGeomHelpers::EmbedMolecule(*mol, ps); CHECK(cid >= 0); } } } TEST_CASE("Sequential random seeds") { SECTION("basics") { auto mol = "CCCCCCCCCCCC"_smiles; REQUIRE(mol); MolOps::addHs(*mol); RWMol mol2(*mol); DGeomHelpers::EmbedParameters ps = DGeomHelpers::ETKDGv3; ps.enableSequentialRandomSeeds = true; ps.useRandomCoords = true; ps.randomSeed = 0xf00d; auto cids = DGeomHelpers::EmbedMultipleConfs(*mol, 10, ps); CHECK(cids.size() == 10); ps.randomSeed = 0xf00d + 5; auto cids2 = DGeomHelpers::EmbedMultipleConfs(mol2, 5, ps); CHECK(cids2.size() == 5); compareConfs(mol.get(), &mol2, 5, 0); } }