content: /*
   * Copyright (c) 1997 - 2022
   * Idorsia Pharmaceuticals Ltd.
   * Hegenheimermattweg 91
   * 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 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.prediction;
  
  import com.actelion.research.calc.ThreadMaster;
  import com.actelion.research.chem.IDCodeParser;
  import com.actelion.research.chem.SSSearcher;
  import com.actelion.research.chem.SSSearcherWithIndex;
  import com.actelion.research.chem.StereoMolecule;
  
  public class DruglikenessPredictorWithIndex {
  	public static final double cDruglikenessUnknown = -999;
  
  	private static IncrementTableWithIndex	sIncrementTable;
      private static boolean					sInitialized = false;
  	private static StereoMolecule[]			sFragmentList;
  
  	public DruglikenessPredictorWithIndex() {
  		synchronized(DruglikenessPredictorWithIndex.class) {
  			if (!sInitialized) {
  		        try {
  					sIncrementTable = new IncrementTableWithIndex("/resources/druglikeness.txt");
  					sFragmentList = new StereoMolecule[sIncrementTable.getSize()];
  					for (int i=0; i<sIncrementTable.getSize(); i++)
  						sFragmentList[i] = new IDCodeParser(false).getCompactMolecule(sIncrementTable.getFragment(i));
  					sInitialized = true;
  					}
  				catch (Exception e) {
  		            System.out.println("Unable to initialize DruglikenessPredictor");
  					}
  				}
  			}
  		}
  
  	/**
  	 * Before calculating any kind of property, make sure that the molecule's structure is standardized.
  	 * Typically, molecules created by an IDCodeParser are standardized. Molecules generated from a
  	 * SmilesParser or MolfileParser, or just drawn within an editor, should be standardized using the
  	 * MoleculeStandardizer.
  	 * @param mol
  	 * @return druglikeness value estimated from atom type specific increments
  	 */
  	public double assessDruglikeness(StereoMolecule mol, long[] index, ThreadMaster threadMaster) {
  		if (!sInitialized)
  			return cDruglikenessUnknown;
  
  		double nastyIncrementSum = 0.0;
  		double incrementSum = 0.0;
  		int fragmentCount = 0;
  		SSSearcherWithIndex swi = new SSSearcherWithIndex(SSSearcher.cMatchAtomCharge);
  		swi.setMolecule(mol, index);
  		for (int i=0; i<sIncrementTable.getSize(); i++) {
  			if (threadMaster != null && threadMaster.threadMustDie())
  				return cDruglikenessUnknown;
  
  			swi.setFragment(sFragmentList[i], sIncrementTable.getIndex(i));
  			if (swi.isFragmentInMolecule()) {
  				double increment = sIncrementTable.getIncrement(i);
  				if (increment < -1)
  					nastyIncrementSum += increment;
  				else {
  					incrementSum += increment;
  					fragmentCount++;
  					}
  				}
  			}
  
  		if (fragmentCount == 0)
  			return -1;
  
  		double druglikeness = nastyIncrementSum + incrementSum / Math.sqrt(fragmentCount);
  
  			// correct cut-off by also treating molecules
  			// with more than 50 found fragments as more drug-like
  		druglikeness = druglikeness + 0.0625 * (fragmentCount - 40);
  
  		return druglikeness;
  		}
  	}
  