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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.
*
*/
package com.actelion.research.chem;
import com.actelion.research.util.IntArrayComparator;
import java.util.ArrayDeque;
import java.util.ArrayList;
import java.util.Iterator;
import java.util.TreeSet;
public class TautomerHelper {
private static final int MAX_TAUTOMERS = 100000;
private StereoMolecule mOriginalMol;
private boolean[] mIsTautomerBond;
private boolean[] mHasFreeValence;
private int[] mRegionPiCount;
private int[] mRegionDCount;
private int[] mRegionTCount;
private Iterator mBondOrderIterator;
private TreeSet mBondOrderSet;
private ArrayDeque mBondOrderDeque;
/**
* @param mol
*/
public TautomerHelper(StereoMolecule mol) {
mOriginalMol = mol;
mOriginalMol.ensureHelperArrays(Molecule.cHelperParities);
mIsTautomerBond = new boolean[mOriginalMol.getBonds()];
mHasFreeValence = new boolean[mOriginalMol.getAtoms()];
for (int i=0; i
* 0: not member of a tautomer region; 1 and above: region number
* @param atomRegionNo int[mol.getAtoms()] filled with 0
* @return region count
*/
public int getAtomRegionNumbers(int[] atomRegionNo) {
if (mBondOrderSet.size() == 1)
return 0;
int regionCount = assignRegionNumbers(atomRegionNo);
return regionCount;
}
/**
* Considers connected tautomer bonds to belong to a tautomer region.
* All independent tautomer regions are located and member atoms assigned to them.
* mAtomRegionNo[] is set accordingly.
* 0: not member of a tautomer region; 1 and above: region number
* @param atomRegionNo int[mol.getAtoms()] filled with 0
* @return number of found tautomer regions
*/
private int assignRegionNumbers(int[] atomRegionNo) {
int[] graphAtom = new int[mOriginalMol.getAtoms()];
boolean[] bondWasSeen = new boolean[mOriginalMol.getBonds()];
int region = 0;
for (int bond=0; bond();
mBondOrderDeque = new ArrayDeque<>();
addTautomerIfNew(new BondOrders(mOriginalMol));
// This serves as recycled molecule container
StereoMolecule tautomer = mOriginalMol.getCompactCopy();
while (!mBondOrderDeque.isEmpty()) {
mBondOrderDeque.poll().copyToTautomer(tautomer);
addAllTautomers(tautomer);
if (mBondOrderSet.size() >= MAX_TAUTOMERS) {
System.out.println("Tautomer count exceeds maximum: "+new Canonizer(mOriginalMol).getIDCode());
break;
}
}
// TODO racemize stereo centers
}
/**
* Find all HX-Y=Z / X=Y-ZH type 3-atom sequences and recursively vinylogous sequences.
*/
private void addAllTautomers(StereoMolecule mol) {
ArrayList bondList = new ArrayList<>();
mol.ensureHelperArrays(Molecule.cHelperNeighbours);
boolean [] isUsedAtom = new boolean[mol.getAtoms()]; // atom use buffer for recursive methods
for (int atom1=0; atom1= order23) {
if (mol.getAtomPi(atom3) < order23) { // if atom3 has no other double bond
if (hasAcidicHydrogen(mol, atom3))
addVinylogousTautomers(mol, atom3, true, false, isUsedAtom, bondList);
}
else {
addVinylogousTautomers(mol, atom3, true, true, isUsedAtom, bondList);
}
}
if (order23 >= order12 && hasAcidicHydrogen(mol, atom1)) {
addVinylogousTautomers(mol, atom3, false, false, isUsedAtom, bondList);
}
if (isValidDonorAtom(atom3)
&& mol.getAtomPi(atom3) < order23) { // make sure atom3 has no other double bond
if (order12<=2 && order23>=2 && hasAcidicHydrogen(mol, atom1)) {
addDirectTautomer(mol, bond12, bond23);
}
if (order12>=2 && order23<=2 && hasAcidicHydrogen(mol, atom3)) {
addDirectTautomer(mol, bond23, bond12);
}
}
bondList.remove(bondList.size()-1);
}
isUsedAtom[atom3] = false;
}
}
bondList.remove(bondList.size()-1);
isUsedAtom[atom2] = false;
}
}
isUsedAtom[atom1] = false;
}
}
}
private boolean isValidDonorAtom(int atom) {
return mHasFreeValence[atom]
&& (mOriginalMol.getAtomicNo(atom) == 5
|| mOriginalMol.getAtomicNo(atom) == 6
|| mOriginalMol.getAtomicNo(atom) == 7
|| mOriginalMol.getAtomicNo(atom) == 8
|| mOriginalMol.getAtomicNo(atom) == 16);
}
private boolean isValidHeteroAtom(int atom) {
return mHasFreeValence[atom]
&& (mOriginalMol.getAtomicNo(atom) == 7
|| mOriginalMol.getAtomicNo(atom) == 8
|| mOriginalMol.getAtomicNo(atom) == 16);
}
private void addDirectTautomer(StereoMolecule mol, int bondSToD, int bondDToS) {
BondOrders bondOrders = new BondOrders(mol);
bondOrders.setBond(bondSToD, mol.getBondOrder(bondSToD) == 1 ? 2 : 3);
bondOrders.setBond(bondDToS, mol.getBondOrder(bondDToS) == 2 ? 1 : 2);
mIsTautomerBond[bondSToD] = true;
mIsTautomerBond[bondDToS] = true;
addTautomerIfNew(bondOrders);
}
private boolean addVinylogousTautomers(StereoMolecule mol, int atom1, boolean firstBondIsDouble, boolean thirdBondIsDouble, boolean[] isUsedAtom, ArrayList bondList) {
for (int i=0; i= 2)
|| (!firstBondIsDouble && order12 <= 2)) {
isUsedAtom[atom2] = true;
bondList.add(bond12);
for (int j=0; j= 2))) {
isUsedAtom[atom3] = true;
bondList.add(bond23);
if (isValidDonorAtom(atom3) && (!firstBondIsDouble || hasAcidicHydrogen(mol, atom3))) {
BondOrders bondOrders = new BondOrders(mol);
for (int k=0; k {
private int[] encoding;
public BondOrders(StereoMolecule mol) {
encoding = new int[(mOriginalMol.getBonds()+15) / 16];
for (int i=0; i> 4] |= (mol.getBondOrder(i) << (2*(i & 15)));
}
@Override
public int compareTo(BondOrders o) {
return new IntArrayComparator().compare(encoding, o.encoding);
}
public void setBond(int bond, int order) {
int high = bond >> 4;
int shift = 2 * (bond & 15);
encoding[high] &= ~(3 << shift);
encoding[high] |= (order << shift);
}
public void copyToTautomer(StereoMolecule tautomer) {
for (int i=0; i> 4] >> (2*(i & 15)));
tautomer.setBondType(i, bo == 1 ? Molecule.cBondTypeSingle
: bo == 2 ? Molecule.cBondTypeDouble
: bo == 3 ? Molecule.cBondTypeTriple
: Molecule.cBondTypeMetalLigand);
}
}
}
}
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