// $Id$ // // Copyright (C) 2004-2012 Greg Landrum and Rational Discovery LLC // // @@ 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 #include #include #include #include "MolDescriptors.h" #include "Crippen.h" #include #include #include #include #include #include typedef boost::tokenizer > tokenizer; #include #include #include #include #include namespace RDKit { namespace Descriptors { extern const std::string defaultParamData; void getCrippenAtomContribs(const ROMol &mol, std::vector &logpContribs, std::vector &mrContribs, bool force, std::vector *atomTypes, std::vector *atomTypeLabels) { PRECONDITION(logpContribs.size() == mol.getNumAtoms() && mrContribs.size() == mol.getNumAtoms(), "bad result vector size"); PRECONDITION((!atomTypes || atomTypes->size() == mol.getNumAtoms()), "bad atomTypes vector"); PRECONDITION((!atomTypeLabels || atomTypeLabels->size() == mol.getNumAtoms()), "bad atomTypeLabels vector"); if (!force && mol.hasProp(common_properties::_crippenLogPContribs)) { std::vector tmpVect1, tmpVect2; mol.getProp(common_properties::_crippenLogPContribs, tmpVect1); mol.getProp(common_properties::_crippenMRContribs, tmpVect2); if (tmpVect1.size() == mol.getNumAtoms() && tmpVect2.size() == mol.getNumAtoms()) { logpContribs = tmpVect1; mrContribs = tmpVect2; return; } } boost::dynamic_bitset<> atomNeeded(mol.getNumAtoms()); atomNeeded.set(); const CrippenParamCollection *params = CrippenParamCollection::getParams(); for (const auto ¶m : *params) { std::vector matches; SubstructMatch(mol, *(param.dp_pattern.get()), matches, false, true); for (std::vector::const_iterator matchIt = matches.begin(); matchIt != matches.end(); ++matchIt) { int idx = (*matchIt)[0].second; if (atomNeeded[idx]) { atomNeeded[idx] = 0; logpContribs[idx] = param.logp; mrContribs[idx] = param.mr; if (atomTypes) (*atomTypes)[idx] = param.idx; if (atomTypeLabels) (*atomTypeLabels)[idx] = param.label; } } // no need to keep matching stuff if we already found all the atoms: if (atomNeeded.none()) break; } mol.setProp(common_properties::_crippenLogPContribs, logpContribs, true); mol.setProp(common_properties::_crippenMRContribs, mrContribs, true); } void calcCrippenDescriptors(const ROMol &mol, double &logp, double &mr, bool includeHs, bool force) { if (!force && mol.hasProp(common_properties::_crippenLogP)) { mol.getProp(common_properties::_crippenLogP, logp); mol.getProp(common_properties::_crippenMR, mr); return; } // this isn't as bad as it looks, we aren't actually going // to harm the molecule in any way! ROMol *workMol = const_cast(&mol); if (includeHs) { workMol = MolOps::addHs(mol, false, false); } std::vector logpContribs(workMol->getNumAtoms()); std::vector mrContribs(workMol->getNumAtoms()); getCrippenAtomContribs(*workMol, logpContribs, mrContribs, force); logp = 0.0; for (std::vector::const_iterator iter = logpContribs.begin(); iter != logpContribs.end(); ++iter) { logp += *iter; } mr = 0.0; for (std::vector::const_iterator iter = mrContribs.begin(); iter != mrContribs.end(); ++iter) { mr += *iter; } if (includeHs) { delete workMol; } mol.setProp(common_properties::_crippenLogP, logp, true); mol.setProp(common_properties::_crippenMR, mr, true); }; double calcClogP(const ROMol &mol) { double clogp,mr; calcCrippenDescriptors(mol, clogp, mr); return clogp; } double calcMR(const ROMol &mol) { double clogp,mr; calcCrippenDescriptors(mol, clogp, mr); return mr; } typedef boost::flyweight< boost::flyweights::key_value, boost::flyweights::no_tracking> param_flyweight; const CrippenParamCollection *CrippenParamCollection::getParams( const std::string ¶mData) { const CrippenParamCollection *res = &(param_flyweight(paramData).get()); return res; } CrippenParamCollection::CrippenParamCollection(const std::string ¶mData) { std::string params; boost::char_separator tabSep("\t", "", boost::keep_empty_tokens); if (paramData == "") params = defaultParamData; else params = paramData; std::istringstream inStream(params); std::string inLine = RDKit::getLine(inStream); unsigned int idx = 0; while (!inStream.eof()) { if (inLine[0] != '#') { CrippenParams paramObj; paramObj.idx = idx++; tokenizer tokens(inLine, tabSep); tokenizer::iterator token = tokens.begin(); paramObj.label = *token; ++token; paramObj.smarts = *token; ++token; if (*token != "") { paramObj.logp = boost::lexical_cast(*token); } else { paramObj.logp = 0.0; } ++token; if (*token != "") { try { paramObj.mr = boost::lexical_cast(*token); } catch (boost::bad_lexical_cast &) { paramObj.mr = 0.0; } } else { paramObj.mr = 0.0; } paramObj.dp_pattern = boost::shared_ptr(SmartsToMol(paramObj.smarts)); d_params.push_back(paramObj); } inLine = RDKit::getLine(inStream); } } CrippenParams::~CrippenParams() { dp_pattern.reset(); } const std::string defaultParamData = "#ID SMARTS logP MR Notes/Questions\n" "C1 [CH4] 0.1441 2.503 \n" "C1 [CH3]C 0.1441 2.503 \n" "C1 [CH2](C)C 0.1441 2.503 \n" "C2 [CH](C)(C)C 0 2.433 \n" "C2 [C](C)(C)(C)C 0 2.433 \n" "C3 [CH3][N,O,P,S,F,Cl,Br,I] -0.2035 2.753 \n" "C3 [CH2X4]([N,O,P,S,F,Cl,Br,I])[A;!#1] -0.2035 2.753 \n" "C4 [CH1X4]([N,O,P,S,F,Cl,Br,I])([A;!#1])[A;!#1] -0.2051 2.731 \n" "C4 [CH0X4]([N,O,P,S,F,Cl,Br,I])([A;!#1])([A;!#1])[A;!#1] -0.2051 " "2.731 \n" "C5 [C]=[!C;A;!#1] -0.2783 5.007 \n" "C6 [CH2]=C 0.1551 3.513 \n" "C6 [CH1](=C)[A;!#1] 0.1551 3.513 \n" "C6 [CH0](=C)([A;!#1])[A;!#1] 0.1551 3.513 \n" "C6 [C](=C)=C 0.1551 3.513 \n" "C7 [CX2]#[A;!#1] 0.0017 3.888 \n" "C8 [CH3]c 0.08452 2.464 \n" "C9 [CH3]a -0.1444 2.412 \n" "C10 [CH2X4]a -0.0516 2.488 \n" "C11 [CHX4]a 0.1193 2.582 \n" "C12 [CH0X4]a -0.0967 2.576 \n" "C13 [cH0]-[A;!C;!N;!O;!S;!F;!Cl;!Br;!I;!#1] -0.5443 4.041 \n" "C14 [c][#9] 0 3.257 \n" "C15 [c][#17] 0.245 3.564 \n" "C16 [c][#35] 0.198 3.18 \n" "C17 [c][#53] 0 3.104 \n" "C18 [cH] 0.1581 3.35 \n" "C19 [c](:a)(:a):a 0.2955 4.346 \n" "C20 [c](:a)(:a)-a 0.2713 3.904 \n" "C21 [c](:a)(:a)-C 0.136 3.509 \n" "C22 [c](:a)(:a)-N 0.4619 4.067 \n" "C23 [c](:a)(:a)-O 0.5437 3.853 \n" "C24 [c](:a)(:a)-S 0.1893 2.673 \n" "C25 [c](:a)(:a)=[C,N,O] -0.8186 3.135 \n" "C26 [C](=C)(a)[A;!#1] 0.264 4.305 \n" "C26 [C](=C)(c)a 0.264 4.305 \n" "C26 [CH1](=C)a 0.264 4.305 \n" "C26 [C]=c 0.264 4.305 \n" "C27 [CX4][A;!C;!N;!O;!P;!S;!F;!Cl;!Br;!I;!#1] 0.2148 " "2.693 " "\n" "CS [#6] 0.08129 3.243 \n" "H1 [#1][#6,#1] 0.123 1.057 \n" "H2 [#1]O[CX4,c] -0.2677 1.395 \n" "H2 [#1]O[!#6;!#7;!#8;!#16] -0.2677 1.395 \n" "H2 [#1][!#6;!#7;!#8] -0.2677 1.395 \n" "H3 [#1][#7] 0.2142 0.9627 \n" "H3 [#1]O[#7] 0.2142 0.9627 \n" "H4 [#1]OC=[#6,#7,O,S] 0.298 1.805 \n" "H4 [#1]O[O,S] 0.298 1.805 \n" "HS [#1] 0.1125 1.112 \n" "N1 [NH2+0][A;!#1] -1.019 2.262 \n" "N2 [NH+0]([A;!#1])[A;!#1] -0.7096 2.173 \n" "N3 [NH2+0]a -1.027 2.827 \n" "N4 [NH1+0]([!#1;A,a])a -0.5188 3 \n" "N5 [NH+0]=[!#1;A,a] 0.08387 1.757 \n" "N6 [N+0](=[!#1;A,a])[!#1;A,a] 0.1836 2.428 \n" "N7 [N+0]([A;!#1])([A;!#1])[A;!#1] -0.3187 1.839 \n" "N8 [N+0](a)([!#1;A,a])[A;!#1] -0.4458 2.819 \n" "N8 [N+0](a)(a)a -0.4458 2.819 \n" "N9 [N+0]#[A;!#1] 0.01508 1.725 \n" "N10 [NH3,NH2,NH;+,+2,+3] -1.95 \n" "N11 [n+0] -0.3239 2.202 \n" "N12 [n;+,+2,+3] -1.119 \n" "N13 [NH0;+,+2,+3]([A;!#1])([A;!#1])([A;!#1])[A;!#1] -0.3396 " "0.2604 " "\n" "N13 [NH0;+,+2,+3](=[A;!#1])([A;!#1])[!#1;A,a] -0.3396 " "0.2604 " "\n" "N13 [NH0;+,+2,+3](=[#6])=[#7] -0.3396 0.2604 \n" "N14 [N;+,+2,+3]#[A;!#1] 0.2887 3.359 \n" "N14 [N;-,-2,-3] 0.2887 3.359 \n" "N14 [N;+,+2,+3](=[N;-,-2,-3])=N 0.2887 3.359 \n" "NS [#7] -0.4806 2.134 \n" "O1 [o] 0.1552 1.08 \n" "O2 [OH,OH2] -0.2893 0.8238 \n" "O3 [O]([A;!#1])[A;!#1] -0.0684 1.085 \n" "O4 [O](a)[!#1;A,a] -0.4195 1.182 \n" "O5 [O]=[#7,#8] 0.0335 3.367 \n" "O5 [OX1;-,-2,-3][#7] 0.0335 3.367 \n" "O6 [OX1;-,-2,-2][#16] -0.3339 0.7774 \n" "O6 [O;-0]=[#16;-0] -0.3339 0.7774 \n" "O12 [O-]C(=O) -1.326 \"order flip here " "intentional\"\n" "O7 [OX1;-,-2,-3][!#1;!N;!S] -1.189 0 \n" "O8 [O]=c 0.1788 3.135 \n" "O9 [O]=[CH]C -0.1526 0 \n" "O9 [O]=C(C)([A;!#1]) -0.1526 0 \n" "O9 [O]=[CH][N,O] -0.1526 0 \n" "O9 [O]=[CH2] -0.1526 0 \n" "O9 [O]=[CX2]=O -0.1526 0 \n" "O10 [O]=[CH]c 0.1129 0.2215 \n" "O10 [O]=C([C,c])[a;!#1] 0.1129 0.2215 \n" "O10 [O]=C(c)[A;!#1] 0.1129 0.2215 \n" "O11 [O]=C([!#1;!#6])[!#1;!#6] 0.4833 0.389 \n" "OS [#8] -0.1188 0.6865 \n" "F [#9-0] 0.4202 1.108 \n" "Cl [#17-0] 0.6895 5.853 \n" "Br [#35-0] 0.8456 8.927 \n" "I [#53-0] 0.8857 14.02 \n" "Hal [#9,#17,#35,#53;-] -2.996 \n" "Hal [#53;+,+2,+3] -2.996 \n" "Hal [+;#3,#11,#19,#37,#55] -2.996 \"Footnote h indicates " "these should be here?\"\n" "P [#15] 0.8612 6.92 \n" "S2 [S;-,-2,-3,-4,+1,+2,+3,+5,+6] -0.0024 7.365 \"Order flip " "here is intentional\"\n" "S2 [S-0]=[N,O,P,S] -0.0024 7.365 \"Expanded definition of " "(pseudo-)ionic S\"\n" "S1 [S;A] 0.6482 7.591 \"Order flip here is intentional\"\n" "S3 [s;a] 0.6237 6.691 \n" "Me1 [#3,#11,#19,#37,#55] -0.3808 5.754 \n" "Me1 [#4,#12,#20,#38,#56] -0.3808 5.754 \n" "Me1 [#5,#13,#31,#49,#81] -0.3808 5.754 \n" "Me1 [#14,#32,#50,#82] -0.3808 5.754 \n" "Me1 [#33,#51,#83] -0.3808 5.754 \n" "Me1 [#34,#52,#84] -0.3808 5.754 \n" "Me2 [#21,#22,#23,#24,#25,#26,#27,#28,#29,#30] -0.0025 " " " "\n" "Me2 [#39,#40,#41,#42,#43,#44,#45,#46,#47,#48] -0.0025 " " " "\n" "Me2 [#72,#73,#74,#75,#76,#77,#78,#79,#80] -0.0025 \n"; } // end of namespace Descriptors }