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Open Source Chemistry Library
/*
* Copyright (c) 1997 - 2016
* Actelion Pharmaceuticals Ltd.
* Gewerbestrasse 16
* CH-4123 Allschwil, Switzerland
*
* All rights reserved.
*
* Redistribution and use in source and binary forms, with or without
* modification, are permitted provided that the following conditions are met:
*
* 1. Redistributions of source code must retain the above copyright notice, this
* list of conditions and the following disclaimer.
* 2. 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.
* 3. Neither the name of the the copyright holder 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.
*
* @author Thomas Sander
*/
package com.actelion.research.chem.reaction.mapping;
import com.actelion.research.chem.Molecule;
import com.actelion.research.chem.SSSearcher;
import com.actelion.research.chem.StereoMolecule;
import com.actelion.research.chem.reaction.IReactionMapper;
import com.actelion.research.chem.reaction.Reaction;
public class ChemicalRuleEnhancedReactionMapper implements IReactionMapper {
private static final int MAX_MATCH_COUNT = 512; // Protection for combinatorial explosion, e.g. for metathesis or DielsAlder in fullerene
// Chemical rule reactions must neither be stoichiometrically complete, nor must they be completely mapped!!!
// If rules contain exclude atoms, these must not be mapped.
// Of course, when a rule is applied, then only the mapped region of the rule is used as a template to
// change bonding of the reaction the rule is applied to. Nevertheless, the rule's entire reactant is used
// for the substructure search that identifies applicability.
private static final ChemicalRule[] CHEMICAL_RULE = {
new ChemicalRule("d","gGQ@@eKtrAkDH!gGQ@@djsRIKVPP#qMsT qM\\V#!R_yL@dw~l@Jp@dsNR_@", 3.5f),
new ChemicalRule("e","daXJ@@PjyITuiX@`!dahJ@@SJYIMMfPB#IaLJfxP IaAhl[`#!ROrp?Ds|lOqNk?g?l_zLsSGp", 1.5f),
// bad new ChemicalRule("f","gJQ`@bdjt`P!gKa`@ldfrA@#qbqh qqlP#!R_zq?dw~l_yLsXgp", 0.5f),
new ChemicalRule("g","gBa`@lde@XS@!gCA`@mDPOdku`#qbq qJt#!R_zq?dxgFLvHB", 5.5f),
// no evidence new ChemicalRule("h","daXL@@Klb`JSSHA@!daXL@@[dfTBijh@`#IyjFDp` IyjEL``#!R?g~HO[\\}[Lfw?K_}m?psLap", 7.5f),
// evidences covered by aldol new ChemicalRule("aldolEnoneCyclisation","daXD@@kHh`Ttl@P!daxD@@yIeRfZZ`B#IqBbay` IqHKjXP#!R_g}wwWC]]xKCfXbBbMtshep", 6.5f),
// fishy new ChemicalRule("j","gBi@DDcXCnR`!gBi@HDFXCnY`#qbq qfQ#!R_vpy`W}lLvK|", 3.5f),
// no evidence new ChemicalRule("l","daxH@@RUUjjPB!daDH@@RVU[jij@H#IGfhlR@ IGfbdK@#!R@IL@k@BS@Jp@dpBl@ILs|kp", 0.5f),
// no evidence new ChemicalRule("m","gFQHBGAISiPH!gGQHJGAIUjhB#qNT] qNTk#!R@AL@[@@Sa_x@DsNro@", 0.5f),
// no evidence new ChemicalRule("n","gOp`@|dRaqij`H!gOp`@tiUMij`H#qosJ` qgSqh#!RTv]`YRqg?g~HPh`}L{H|", 0.5f),
new ChemicalRule("o","gGQHDDqIUjdB!gGQHHDqAeMjhB#qbqk qfQ]#!R_zq?dw~l_yM?kCM|?@", 0.5f),
// no evidence new ChemicalRule("p","gGQ@@eJuRA@!gFQ@@diuPD#qqUc qrcM#!R_zp@kG~S@IM?kCLb?@", 5.5f),
new ChemicalRule("r","gOQdEjHbAFQRBrtAaJ!gNQdEbHbABCTKPFDH#qbMwX qbM~X#!RCwpb@@M`CpL}cg@CL|jB", 0.5f),
new ChemicalRule("s","gOp`ATigujj`H!gOp`ATiVKjj`H#qnyS` qY~eP#!R?`@_YQ|ZFBqSFHc}L{IB", 0.5f),
new ChemicalRule("t","gOP`@dcUZdB!gNp`@tiTMjj@`#q{ir` qkLrx#!R@ANZXPAl@AL@[@@SLtj|", 0.5f),
new ChemicalRule("u","daXB`Hrn@HrPEILt`D!daXB`DJn@HRUMjV@H#IxVaLJ` IylJhPP#!R_zL@hs`Q_zq?dw~l_yLsBkp", 0.5f),
new ChemicalRule("Sakurai", "gOQH@wAINvZ@pdcFe@x@!gOQH@wAIgJi@pdcFe@x@#qreKx qrLkx#!R_g~HO_fQbOvw?[_|L}r\\", 4.5f),
new ChemicalRule("Mitsunobu", "gFP`ATfRjdPp`}KEYg]d@!gFP`ATfRjd`pekL{l`#qrLk qZLn#!Rw`Bg?Hc|i}uUYcMb``", 4.5f),
new ChemicalRule("Aldol-Addition", "gOQ@AdTAcS@^Pvb}GdThXJg@HUfI\u007FlP!gGQ@@dsuRAcJg@HUaH#qYEbp qYub#!Rw[\\\\mw?^akFC|CtwLtI\\", 1.5f),
new ChemicalRule("Aldol-Condensation", "gOQ@AdTAcS@^Pvb}GdThXJg@HUfI\u007FlP!gFQ@@`rrpdlHHpipBEXb@#qYEbp q^aU#!Rw[\\\\mw?^akFC|CtwLtI\\", 2.5f),
new ChemicalRule("Acetal-Aldol-Addition", "dmdB@@serQS@sJjfd@p`Xir\\@`j\\@aUJHI@!daxL@@[df[ZjT@qQdxACdxABjTQb@#qB@`OuX qBtM{#!RM?rH?C]}_`CW?Ev^@T@wwS^B_`@sHop", 1.5f),
new ChemicalRule("Acetal-Aldol-Condensation", "dmdB@@serQS@sJjfd@p`Xir\\@`j\\@aUJHI@!gNp`CTjUiV@qQS`DJg@HUVHR@#qB@`OuX qqj{`#!RM?rH?C]}_`CW?Ev^@T@wwS^B_`@sHop", 1.5f),
new ChemicalRule("Acetal-Aldol-Condensation-Cyclization", "dkLB@@ZURYUvUjejhHYpaHpr\\@aUJHp`!didD@@EIfU[hBA@CFAS`DJqq@#IXljNPY@@@ IXljXxT#!R_`CW@h`BuwvH_[yOb@I~@M_|bOsW_Wx@LuJb", 7.5f),
new ChemicalRule("Enolester-Cleavage", "gOQ`@fdscT`_Qp!gOQ`@cdTASS@P#q}Kr` q}cNP#!R?g~H?[_}bOrH?WzeLyH\\", 5.3f),
new ChemicalRule("propargylEnone", "gCa@@dmXFD@!gCa@@dkHD#qNT qLV#!RXIq`pp@sLwI|", 5.5f),
new ChemicalRule("Arndt-Eistert", "daiDaJYBBHj^{HhAYMpAaA@!daiD`FzLBHPVsZl@p`@#IyHHZ[@ IzDGBi`#!R@W|h_U\\}X{GUJU\\}TEpsHap", 11.5f),
new ChemicalRule("Curtius", "gO]IcVaDF[s{HhCIe@`!gN]HMWADHJfm`XP@#q~Jk` qytUX#!R?g}HoU_]U\\eWwQ@\\Lwq\\", 9.5f),
new ChemicalRule("diazomethanHomologation", "gFU@lQioIIs\\AyH!gFU@CPdimXD#qbM^ qbqk#!Rk}rop?v~k|L@kKNB@`", 7.5f),
// methathese
new ChemicalRule("ene-Metathesis","daX@@LdPLSSPHEelRXwQIHXLa`ZFChXO}IL[`!daX@@LdPLSSPHEelRXwQIHXLa`ZFChXO}IL[`#qT@q@ qt@Q@#!RNIu^@O{wD^EGhkzO?aBsdcp", 3.5f),
new ChemicalRule("yne-Metathesis","daX@@LdPLWWPAlRXwQIHXLa`ZFChXO}IL[`!daX@@LdPLWWPAlRXwQIHXLa`ZFChXO}IL[`#qT@q@ qt@Q@#!RZmoi@Fjo|SFe|IkGiUBSLop", 3.5f),
new ChemicalRule("ene-yne-Metathesis","dcd@@LdPLPLWSSPIdulrXwKlVRFCHXFa`zFAXXMa`udqnWP!dcT@@LdbbplTsTtFPx}[MeMr{Ela`jFAhXNa`VFCXXO}[J[et#qe@N@S@ qeHP@s@#!R_c}~@Gx?QgF}bKwW@h`yoosW?Hb}usNRO@", 7.5f),
new ChemicalRule("Alkyne-Cyclisation", "gG`@DcO|CFAFC`@!gFp@DiTt@@CFAFC`@#qi\\V qiSt#!Rb@JNyk\\Bl^{~@CORp`", 8.5f),
// two step
new ChemicalRule("Elimination-Claisen", "gNp`AldTQji@~a`!gOP`@teTZdCzN@#qtHUX qtSi@#!RupI~Owx@uwwW_]_|LyK|", 4.5f),
new ChemicalRule("imineFormationAzaCope", "daZH@LAIMUjd@pRL@!daZH@HAAn]jd@p`@#IGfaLJ` IFDzfK@#!RXpAl@HYrXs}lOvL?[C|sTdH", 8.5f),
new ChemicalRule("didehydroCopeWithAromatisation", "gNp@Di]ejDcjbrlwK`!gOp@DjWkB@@H#qrLkx q\\oQp#!R?`Bw?[\\BmpK~@K\\BL~JB", 4.5f),
// multi step with cyclisation/condensation
new ChemicalRule("symAldolNitrogenRing", "dovJ@GBfttf\\v\\qjViPCADGbDodnGp!doNJ@JCSmtefWTCaYjje@H#IlZXi]]yL~C IqMVCzaIim?#!R@hb}b@A~Owz}uzyl_]\\Bus}~@GxBbLfaOwzUicMbX`", 0.5f),
// pericyclic
new ChemicalRule("Diels-Alder","gFP@LdPLjA@!gFp@DiTujhB#qiZf qMSf#!R?`BH?X`BIo[~_sNr``", 3.5f),
new ChemicalRule("Cope", "gGQ@DeZmRAbhcApIF@P@!gGQ@HeZmRAbhc@HIFC`@#qkNT qi\\V#!R@BM_Hu}lWrM_[COBO@", 5.5f),
new ChemicalRule("OxyCope", "gNq@@dr}SHFD@!gNq@@djkUHD#qynZ` qykbp#!Ro`AH`c]|\\KtwoS]|LvIB", 4.5f),
// rearrangements
new ChemicalRule("Vinylcyclopropane", "gKP@DklVj@`!gKP@Di\\Vj@`#qaVh qTqh#!Rm?t@?h`BbOtsdop", 3.5f),
new ChemicalRule("Furan-CH2-OH-Rearrangement", "gOp`@tiguif`H!gOp`@tfWMZZ`H#qZna@ qZtM@#!RTXC@z]BRe?s|bKx@L}KB", 6.5f),
new ChemicalRule("rearrangement1032", "gOp`ATieMji`H!gOp`ATeekZj`H#qaSnx qa]~P#!ROh]`lkoYCONJ_quT|qJl", 5.5f),
// 1,2-shifts
new ChemicalRule("Pinacol-Rearrangement", "gNp`ATffjj@pPh!gOP`@tfXZhCAA`#qb^ix qb^oH#!R?m}WoRb}Og?~wu^BLsH\\", 6.5f),
new ChemicalRule("1,3-WaterEliminationWith12Shift", "gJQ@@dmU@_SP!gKa@@`vtA}A@#qiTp qjap#!R?`ADddRm?basHdH", 6.5f),
// oxidative rearrangements
new ChemicalRule("Epoxydation", "gB``ADcdCB@!gC``AhtUPGtt@#qqb qtQ#!R_vsFWg}lLvK|", 6.3f),
new ChemicalRule("oxydativePropargylAmine13Shift", "gKi@HDEZpLHOQP!gJY@BDeVXQL#qMr` qNTh#!R|Wk@H|@\\@BrStnH", 6.5f),
new ChemicalRule("Baeyer-Villiger", "gFQ`@[dTAZ`LHP!gFQ`@jdrMPGtl@#qrak qrlK#!R?g~H?[_}AZfw?COBG@", 7.5f),
};
private static boolean sInitialized;
private StereoMolecule mReactant,mProduct;
private float mScore;
private int mMaxRuleTries;
private ChemicalRule mAppliedRule;
private StringBuilder mHistory;
public ChemicalRuleEnhancedReactionMapper() {
if (!sInitialized)
synchronized (this.getClass()) {
if (!sInitialized) {
for (ChemicalRule rule:CHEMICAL_RULE)
rule.initialize();
sInitialized = true;
}
}
mMaxRuleTries = Integer.MAX_VALUE;
}
@Override
public Reaction mapReaction(Reaction rxn, SSSearcher sss) {
map(rxn);
return rxn;
}
public void map(Reaction rxn) {
SimilarityGraphBasedReactionMapper mapper = new SimilarityGraphBasedReactionMapper();
mapper.mergeReactantsAndProducts(rxn);
mReactant = mapper.getReactant();
mProduct = mapper.getProduct();
mReactant.ensureHelperArrays(Molecule.cHelperNeighbours);
mProduct.ensureHelperArrays(Molecule.cHelperNeighbours);
// TODO use indexes
SSSearcher reactantSearcher = new SSSearcher();
SSSearcher productSearcher = new SSSearcher();
reactantSearcher.setMolecule(mReactant);
productSearcher.setMolecule(mProduct);
mScore = Integer.MIN_VALUE;
int[] bestReactantMapNo = null;
int[] bestProductMapNo = null;
int bestGraphMapNoCount = 0;
mAppliedRule = null;
int ruleApplicationCount = 0;
mHistory = new StringBuilder();
if (SimilarityGraphBasedReactionMapper.DEBUG)
System.out.println("Reaction\tScore");
StereoMolecule reactant = new StereoMolecule(); // reusable container
for (ChemicalRule rule:CHEMICAL_RULE) {
if (ruleApplicationCount++ == mMaxRuleTries)
break;
reactantSearcher.setFragment(rule.getReactant());
reactantSearcher.setFragmentSymmetryConstraints(rule.getReactantAtomSymmetryConstraints());
if (0 != reactantSearcher.findFragmentInMolecule(SSSearcher.cCountModeUnique, SSSearcher.cDefaultMatchMode)) {
productSearcher.setFragment(rule.getProduct());
if (productSearcher.isFragmentInMolecule()
&& reactantSearcher.getMatchList().size() <= MAX_MATCH_COUNT) {
float historyScore = -10000;
for (int[] reactantMatch:reactantSearcher.getMatchList()) {
if (ruleApplicationCount++ >= mMaxRuleTries)
break;
mReactant.copyMolecule(reactant);
rule.apply(reactant, reactantMatch);
int[] reactantMapNo = new int[mReactant.getAtoms()];
int[] productMapNo = new int[mProduct.getAtoms()];
//System.out.println(new MolfileCreator(reactant).getMolfile());
mapper.map(reactant, mProduct, reactantMapNo, productMapNo);
float score = mapper.getScore() - rule.getPanalty();
if (historyScore < score) historyScore = score;
if (mScore < score) {
mScore = score;
bestReactantMapNo = reactantMapNo;
bestProductMapNo = productMapNo;
bestGraphMapNoCount = mapper.getGraphMapNoCount();
mAppliedRule = rule;
}
}
String pairSequences = mapper.getAtomPairSequenceCount() <= 1 ? "" : " (rootPairSets:"+mapper.getAtomPairSequenceCount()+")";
mHistory.append(rule.getName()+historyScore+pairSequences+"\n");
}
}
}
// map and score the reaction without applying any rules
int[] reactantMapNo = new int[mReactant.getAtoms()];
int[] productMapNo = new int[mProduct.getAtoms()];
mapper.map(mReactant, mProduct, reactantMapNo, productMapNo);
float score = mapper.getScore();
if (mScore <= score) {
mAppliedRule = null;
mScore = score;
bestReactantMapNo = reactantMapNo;
bestProductMapNo = productMapNo;
bestGraphMapNoCount = mapper.getGraphMapNoCount();
}
String pairSequences = mapper.getAtomPairSequenceCount() <= 1 ? "" : " (rootPairSets:"+mapper.getAtomPairSequenceCount()+")";
mHistory.append("no rule:"+score+pairSequences+"\n");
if (mScore != Integer.MIN_VALUE)
mapper.copyMapNosToReaction(rxn, bestReactantMapNo, bestProductMapNo, bestGraphMapNoCount);
if (SimilarityGraphBasedReactionMapper.DEBUG)
System.out.println("Done; used "+ruleApplicationCount+" of "+mMaxRuleTries+" allowed rule application tries.");
}
/**
* This limits the maximum number of times a chemical rule is applied to improve the mapping.
* @param max
*/
public void setMaximumRuleTries(int max) {
mMaxRuleTries = max;
}
public String getHistory() {
return mHistory.toString();
}
public float getScore() {
return mScore;
}
public ChemicalRule getAppliedRule() {
return mAppliedRule;
}
}