content: /*
  * 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.prediction;
  
  import com.actelion.research.calc.ThreadMaster;
  import com.actelion.research.chem.IDCodeParser;
  import com.actelion.research.chem.SSSearcher;
  import com.actelion.research.chem.StereoMolecule;
  
  public class DruglikenessPredictor {
  	public static final double cDruglikenessUnknown = -999;
  
      private static boolean			sInitialized = false;
  	private static IncrementTable	sIncrementTable;
  
  	private ParameterizedStringList	mDetail;
  
  	public DruglikenessPredictor() {
  		synchronized(DruglikenessPredictor.class) {
  			if (!sInitialized) {
  		        try {
  					sIncrementTable = new IncrementTable("/resources/druglikenessNoIndex.txt");
  					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, ThreadMaster threadMaster) {
  		ParameterizedStringList detail = new ParameterizedStringList();
  
  		if (!sInitialized) {
  			detail.add("Druglikeness predictor not properly initialized.",
  								ParameterizedStringList.cStringTypeText);
  			return cDruglikenessUnknown;
  			}
  
  		detail.add("Found sub-structure fragments and their contributions:",
  							ParameterizedStringList.cStringTypeText);
  		detail.add("(yellow atoms carry at least one more substituent)",
  							ParameterizedStringList.cStringTypeText);
  		double nastyIncrementSum = 0.0;
  		double incrementSum = 0.0;
  		int fragmentCount = 0;
  		SSSearcher sss = new SSSearcher(SSSearcher.cMatchAtomCharge);
  		StereoMolecule fragment = new StereoMolecule();
  		for (int i=0; i<sIncrementTable.getSize(); i++) {
  			if (threadMaster != null && threadMaster.threadMustDie())
  				return cDruglikenessUnknown;
  
  			Thread.yield();
  
  			new IDCodeParser(false).parse(fragment, sIncrementTable.getFragment(i));
  			sss.setMol(fragment, mol);
  			if (sss.isFragmentInMolecule()) {
  				double increment = sIncrementTable.getIncrement(i);
  				if (increment < -1)
  					nastyIncrementSum += increment;
  				else {
  					incrementSum += increment;
  					fragmentCount++;
  					}
  
  				detail.add(sIncrementTable.getFragment(i),
  								   ParameterizedStringList.cStringTypeIDCode);
  				detail.add(Double.toString(increment),
  								   ParameterizedStringList.cStringTypeDouble);
  				}
  			}
  
  		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);
  
  		mDetail = detail;
  		return druglikeness;
  		}
  
  	public String getDruglikenessString(StereoMolecule testMolecule) {
  		if (!sInitialized)
  			return "Druglikeness predictor not properly initialized.";
  
  		double incrementSum = 0.0;
  		int fragmentCount = 0;
  		SSSearcher sss = new SSSearcher(SSSearcher.cMatchAtomCharge);
  		StereoMolecule fragment = new StereoMolecule();
  		for (int i=0; i<sIncrementTable.getSize(); i++) {
  			new IDCodeParser(false).parse(fragment, sIncrementTable.getFragment(i));
  			sss.setMol(fragment, testMolecule);
  			if (sss.isFragmentInMolecule()) {
  				incrementSum += sIncrementTable.getIncrement(i);
  				fragmentCount++;
  				}
  			}
  
  		double druglikeness = (fragmentCount == 0) ? -1 : incrementSum / Math.sqrt(fragmentCount);
  		return druglikeness + "\t" + fragmentCount + "\t" + testMolecule.getAtoms();
  		}
  
  	/**
  	 * If assessDruglikeness() was called multiple times in multiple threads, then
  	 * getDetail() won't retrieve the expected detail.
  	 * @return
  	 */
  	public ParameterizedStringList getDetail() {
  		return mDetail;
  		}
  	}
  