smilesgenerator.java

化学图形处理软件

/*  $Revision: 9775 $ $Author: shk3 $ $Date: 2008-01-01 21:23:12 +0100 (Tue, 01 Jan 2008) $
 *  
 *  Copyright (C) 2002-2007  Oliver Horlacher
 *
 *  Contact: [e-mail]
 *
 *  This program is free software; you can redistribute it and/or
 *  modify it under the terms of the GNU Lesser General Public License
 *  as published by the Free Software Foundation; either version 2.1
 *  of the License, or (at your option) any later version.
 *  All we ask is that proper credit is given for our work, which includes
 *  - but is not limited to - adding the above copyright notice to the beginning
 *  of your source code files, and to any copyright notice that you may distribute
 *  with programs based on this work.
 *
 *  This program is distributed in the hope that it will be useful,
 *  but WITHOUT ANY WARRANTY; without even the implied warranty of
 *  MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the
 *  GNU Lesser General Public License for more details.
 *
 *  You should have received a copy of the GNU Lesser General Public License
 *  along with this program; if not, write to the Free Software
 *  Foundation, Inc., 51 Franklin St, Fifth Floor, Boston, MA 02110-1301 USA.
 */
package org.openscience.cdk.smiles;

import org.openscience.cdk.CDKConstants;
import org.openscience.cdk.aromaticity.HueckelAromaticityDetector;
import org.openscience.cdk.config.IsotopeFactory;
import org.openscience.cdk.exception.CDKException;
import org.openscience.cdk.geometry.BondTools;
import org.openscience.cdk.graph.ConnectivityChecker;
import org.openscience.cdk.graph.invariant.CanonicalLabeler;
import org.openscience.cdk.graph.invariant.MorganNumbersTools;
import org.openscience.cdk.interfaces.*;
import org.openscience.cdk.ringsearch.AllRingsFinder;
import org.openscience.cdk.ringsearch.RingPartitioner;
import org.openscience.cdk.tools.manipulator.RingSetManipulator;

import java.io.IOException;
import java.util.*;

/**
 * Generates SMILES strings {@cdk.cite WEI88, WEI89}. It takes into account the
 * isotope and formal charge information of the atoms. In addition to this it
 * takes stereochemistry in account for both Bond's and Atom's. Via the flag 
 * useAromaticity it can be set if only SP2-hybridized atoms shall be set to 
 * lower case (default) or atoms, which are SP2 or aromatic. IMPORTANT: The
 * aromaticity detection for this SmilesGenerator relies on AllRingsFinder,
 * which is known to take very long for some molecules with many cycles or
 * special cyclic topologies. Thus, the AllRingsFinder has a built-in timeout
 * of 5 seconds after which it aborts and throws an Exception. If you want your
 * SMILES generated at any expense, you need to create your own AllRingsFinder,
 * set the timeout to a higher value, and assign it to this SmilesGenerator. In
 * the vast majority of cases, however, the defaults will be fine.
 * If you have a set off ALL rings before, supply this via setRings to speed up generation.
 *
 * @author         Oliver Horlacher
 * @author         Stefan Kuhn (chiral smiles)
 * @cdk.created    2002-02-26
 * @cdk.keyword    SMILES, generator
 * @cdk.module     smiles
 * @cdk.bug        1257438
 * @cdk.bug        1535055
 */
public class SmilesGenerator
{
	//private final static boolean debug = false;

	/**
	 *  The number of rings that have been opened
	 */
	private int ringMarker = 0;

	/**
	 *  Collection of all the bonds that were broken
	 */
	private Vector brokenBonds = new Vector();

	/**
	 *  The isotope factory which is used to write the mass is needed
	 */
	private IsotopeFactory isotopeFactory;

	AllRingsFinder ringFinder;

	/**
	* RingSet that holds all rings of the molecule
	*/
	private IRingSet rings = null; 
	
	/**
	 *  The canonical labler
	 */
	private CanonicalLabeler canLabler = new CanonicalLabeler();
	private final String RING_CONFIG = "stereoconfig";
	private final String UP = "up";
	private final String DOWN = "down";
	private boolean useAromaticityFlag=false;

	/**
	 *  Create the SMILES generator.
	 */
	public SmilesGenerator() {}

	/**
	 *  Tells if a certain bond is center of a valid double bond configuration.
	 *
	 *@param  container  The atomcontainer.
	 *@param  bond       The bond.
	 *@return            true=is a potential configuration, false=is not.
	 */
	public boolean isValidDoubleBondConfiguration(IAtomContainer container, IBond bond)
	{
		IAtom atom0 = bond.getAtom(0);
		IAtom atom1 = bond.getAtom(1);
		java.util.List connectedAtoms = container.getConnectedAtomsList(atom0);
		org.openscience.cdk.interfaces.IAtom from = null;
		for (int i = 0; i < connectedAtoms.size(); i++)
		{
			if ((IAtom)connectedAtoms.get(i) != atom1)
			{
				from = (IAtom)connectedAtoms.get(i);
			}
		}
        boolean[] array = new boolean[container.getBondCount()];
		for (int i = 0; i < array.length; i++)
		{
			array[i] = true;
		}
		if (isStartOfDoubleBond(container, atom0, from, array) && isEndOfDoubleBond(container, atom1, atom0, array) && !bond.getFlag(CDKConstants.ISAROMATIC))
		{
			return (true);
		} else
		{
			return (false);
		}
	}

	/**
	 * Provide a reference to a RingSet that holds ALL rings of the molecule.<BR>
	 * During creation of a SMILES the aromaticity of the molecule has to be detected.
	 * This, in turn, requires the dermination of all rings of the molecule. If this
	 * computationally expensive calculation has been done beforehand, a RingSet can
	 * be handed over to the SmilesGenerator to save the effort of another all-rings-
	 * calculation.
	 *
	 * @param  rings  RingSet that holds ALL rings of the molecule
	 * @return        reference to the SmilesGenerator object this method was called for
	 */
	public SmilesGenerator setRings(IRingSet rings)
	{
	  this.rings = rings;
	  return this;
	} 

	/**
	 *  Generate canonical SMILES from the <code>molecule</code>. This method
	 *  canonicaly lables the molecule but does not perform any checks on the
	 *  chemical validity of the molecule.
	 *  IMPORTANT: A precomputed Set of All Rings (SAR) can be passed to this 
	 *  SmilesGenerator in order to avoid recomputing it. Use setRings() to 
	 *  assign the SAR.
	 *
	 *@param  molecule  The molecule to evaluate
	 *@see              org.openscience.cdk.graph.invariant.CanonicalLabeler#canonLabel(IAtomContainer)
	 */
	public synchronized String createSMILES(IMolecule molecule)
	{
		try
		{
			return (createSMILES(molecule, false, new boolean[molecule.getBondCount()]));
		} catch (CDKException exception)
		{
			// This exception can only happen if a chiral smiles is requested
			return ("");
		}
	}


	/**
	 *  Generate a SMILES for the given <code>Reaction</code>.
	 */
	public synchronized String createSMILES(IReaction reaction) throws CDKException
	{
		StringBuffer reactionSMILES = new StringBuffer();
		IMoleculeSet reactants = reaction.getReactants();
		for (int i = 0; i < reactants.getAtomContainerCount(); i++)
		{
			reactionSMILES.append(createSMILES(reactants.getMolecule(i)));
			if (i + 1 < reactants.getAtomContainerCount())
			{
				reactionSMILES.append('.');
			}
		}
		reactionSMILES.append('>');
		IMoleculeSet agents = reaction.getAgents();
		for (int i = 0; i < agents.getAtomContainerCount(); i++)
		{
			reactionSMILES.append(createSMILES(agents.getMolecule(i)));
			if (i + 1 < agents.getAtomContainerCount())
			{
				reactionSMILES.append('.');
			}
		}
		reactionSMILES.append('>');
		IMoleculeSet products = reaction.getProducts();
		for (int i = 0; i < products.getAtomContainerCount(); i++)
		{
			reactionSMILES.append(createSMILES(products.getMolecule(i)));
			if (i + 1 < products.getAtomContainerCount())
			{
				reactionSMILES.append('.');
			}
		}
		return reactionSMILES.toString();
	}


	/**
	 *  Generate canonical and chiral SMILES from the <code>molecule</code>. This
	 *  method canonicaly lables the molecule but dose not perform any checks on
	 *  the chemical validity of the molecule. The chiral smiles is done like in
	 *  the <a href="http://www.daylight.com/dayhtml/doc/theory/theory.smiles.html">
	 *  daylight theory manual</a> . I did not find rules for canonical and chiral
	 *  smiles, therefore there is no guarantee that the smiles complies to any
	 *  externeal rules, but it is canonical compared to other smiles produced by
	 *  this method. The method checks if there are 2D coordinates but does not
	 *  check if coordinates make sense. Invalid stereo configurations are ignored;
	 *  if there are no valid stereo configuration the smiles will be the same as
	 *  the non-chiral one. Note that often stereo configurations are only complete
	 *  and can be converted to a smiles if explicit Hs are given.
	 *  IMPORTANT: A precomputed Set of All Rings (SAR) can be passed to this 
	 *  SmilesGenerator in order to avoid recomputing it. Use setRings() to 
	 *  assign the SAR.
	 *
	 *@param  molecule                 The molecule to evaluate
	 *@exception  CDKException         At least one atom has no Point2D;
	 *      coordinates are needed for creating the chiral smiles.
	 *@see                             org.openscience.cdk.graph.invariant.CanonicalLabeler#canonLabel(IAtomContainer)
	 */
	public synchronized String createChiralSMILES(IMolecule molecule, boolean[] doubleBondConfiguration) throws CDKException
	{
		return (createSMILES(molecule, true, doubleBondConfiguration));
	}


	/**
	 *  Generate canonical SMILES from the <code>molecule</code>. This method
	 *  canonicaly lables the molecule but dose not perform any checks on the
	 *  chemical validity of the molecule. This method also takes care of multiple
	 *  molecules.
	 *  IMPORTANT: A precomputed Set of All Rings (SAR) can be passed to this 
	 *  SmilesGenerator in order to avoid recomputing it. Use setRings() to 
	 *  assign the SAR.
	 *
	 *@param  molecule                 The molecule to evaluate
	 *@param  chiral                   true=SMILES will be chiral, false=SMILES
	 *      will not be chiral.
	 *@exception  CDKException         At least one atom has no Point2D;
	 *      coordinates are needed for crating the chiral smiles. This excpetion
	 *      can only be thrown if chiral smiles is created, ignore it if you want a
	 *      non-chiral smiles (createSMILES(AtomContainer) does not throw an
	 *      exception).
	 *@see                             org.openscience.cdk.graph.invariant.CanonicalLabeler#canonLabel(IAtomContainer)
	 */
	public synchronized String createSMILES(IMolecule molecule, boolean chiral, boolean doubleBondConfiguration[]) throws CDKException
	{
		IMoleculeSet moleculeSet = ConnectivityChecker.partitionIntoMolecules(molecule);
		if (moleculeSet.getMoleculeCount() > 1)
		{
			StringBuffer fullSMILES = new StringBuffer();
			for (int i = 0; i < moleculeSet.getAtomContainerCount(); i++)
			{
				IMolecule molPart = moleculeSet.getMolecule(i);
				fullSMILES.append(createSMILESWithoutCheckForMultipleMolecules(molPart, chiral, doubleBondConfiguration));
				if (i < (moleculeSet.getAtomContainerCount() - 1))
				{
					// are there more molecules?
					fullSMILES.append('.');
				}
			}
			return fullSMILES.toString();
		} else
		{
			return (createSMILESWithoutCheckForMultipleMolecules(molecule, chiral, doubleBondConfiguration));
		}
	}


	/**
	 *  Generate canonical SMILES from the <code>molecule</code>. This method
	 *  canonicaly lables the molecule but dose not perform any checks on the
	 *  chemical validity of the molecule. Does not care about multiple molecules.
	 *  IMPORTANT: A precomputed Set of All Rings (SAR) can be passed to this 
	 *  SmilesGenerator in order to avoid recomputing it. Use setRings() to 
	 *  assign the SAR.
	 *
	 *@param  molecule                 The molecule to evaluate
	 *@param  chiral                   true=SMILES will be chiral, false=SMILES
	 *      will not be chiral.
	 *@exception  CDKException         At least one atom has no Point2D;
	 *      coordinates are needed for creating the chiral smiles. This excpetion
	 *      can only be thrown if chiral smiles is created, ignore it if you want a
	 *      non-chiral smiles (createSMILES(AtomContainer) does not throw an
	 *      exception).
	 *@see                             org.openscience.cdk.graph.invariant.CanonicalLabeler#canonLabel(IAtomContainer)
	 */
	public synchronized String createSMILESWithoutCheckForMultipleMolecules(IMolecule molecule, boolean chiral, boolean doubleBondConfiguration[]) throws CDKException
	{
		if (molecule.getAtomCount() == 0)
		{
			return "";
		}
		canLabler.canonLabel(molecule);
		brokenBonds.clear();
		ringMarker = 0;
		org.openscience.cdk.interfaces.IAtom start = null;
		for (int i = 0; i < molecule.getAtomCount(); i++)
		{
			org.openscience.cdk.interfaces.IAtom atom = molecule.getAtom(i);
			if (chiral && atom.getPoint2d() == null)
			{
				throw new CDKException("Atom number " + i + " has no 2D coordinates, but 2D coordinates are needed for creating chiral smiles");
			}
			//logger.debug("Setting all VISITED flags to false");
			atom.setFlag(CDKConstants.VISITED, false);
			if (((Long) atom.getProperty("CanonicalLable")).longValue() == 1)
			{
				start = atom;
			}
		}

		//detect aromaticity
		if(rings == null)
		{
			if (ringFinder == null)
			{
				ringFinder = new AllRingsFinder();
			}
			rings = ringFinder.findAllRings(molecule);
		}
		HueckelAromaticityDetector.detectAromaticity(molecule, rings, false);
		if (chiral && rings.getAtomContainerCount() > 0)
		{
			List v = RingPartitioner.partitionRings(rings);
			//logger.debug("RingSystems: " + v.size());
			for (int i = 0; i < v.size(); i++)
			{
				int counter = 0;
				Iterator containers = RingSetManipulator.getAllAtomContainers((IRingSet) v.get(i)).iterator();
				while (containers.hasNext()) {
					IAtomContainer allrings = (IAtomContainer) containers.next();
					for (int k = 0; k < allrings.getAtomCount(); k++)
					{
						if (!BondTools.isStereo(molecule, allrings.getAtom(k)) && hasWedges(molecule, allrings.getAtom(k)) != null)
						{
							IBond bond = molecule.getBond(allrings.getAtom(k), hasWedges(molecule, allrings.getAtom(k)));
							if (bond.getStereo() == CDKConstants.STEREO_BOND_UP)
							{
								allrings.getAtom(k).setProperty(RING_CONFIG, UP);
							} else
							{
								allrings.getAtom(k).setProperty(RING_CONFIG, DOWN);
							}
							counter++;
						}
					}
					if (counter == 1)
					{
						for (int k = 0; k < allrings.getAtomCount(); k++)
						{
							IBond bond = molecule.getBond(allrings.getAtom(k), hasWedges(molecule, allrings.getAtom(k)));
							if(bond!=null){
								if (bond.getStereo() == CDKConstants.STEREO_BOND_UP)