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.chem.AtomFunctionAnalyzer;
  import com.actelion.research.chem.Molecule;
  import com.actelion.research.chem.StereoMolecule;
  import com.actelion.research.chem.conf.MolecularFlexibilityCalculator;
  
  public class MolecularPropertyHelper {
  	public static final int MOLECULAR_PROPERTY_MOLWEIGHT = 0;
  	public static final int MOLECULAR_PROPERTY_NON_H_ATOMS = 1;
  	public static final int MOLECULAR_PROPERTY_CLOGP = 2;
  	public static final int MOLECULAR_PROPERTY_CLOGS = 3;
  	public static final int MOLECULAR_PROPERTY_TPSA = 4;
  	public static final int MOLECULAR_PROPERTY_HDONORS = 5;
  	public static final int MOLECULAR_PROPERTY_HACCEPTORS = 6;
  	public static final int MOLECULAR_PROPERTY_FLEXIBILITY = 7;
  	public static final int MOLECULAR_PROPERTY_COMPLEXITY = 8;
  	public static final int MOLECULAR_PROPERTY_SHAPE = 9;
  	public static final int MOLECULAR_PROPERTY_ROTATABLEBONDS = 10;
  	public static final int MOLECULAR_PROPERTY_STEREOCENTERS = 11;
  	public static final int MOLECULAR_PROPERTY_SMALLRINGCOUNT = 12;
  	public static final int MOLECULAR_PROPERTY_AROMRINGCOUNT = 13;
  	public static final int MOLECULAR_PROPERTY_BASIC_NITROGENS = 14;
  	public static final int MOLECULAR_PROPERTY_ACIDIC_OXYGENS = 15;
  	public static final int MOLECULAR_PROPERTY_TOXICITY_RISK = 16;
  
  	// Fitness between min and max is 1.0. Fitness at min-halfWidth or max+halfWidth is 1.0/e
  	// rangeMin and rangeMax are used as limits for the graph depicting the fuzzy score
  	private static final PropertySpecification[] SPEC = {
  			new PropertySpecification("molweight", "Molecular weight", "", "400", 50f, 0f, 800f),
  			new PropertySpecification("nonHAtoms", "non-H atom count", "", "25", 3f, 0f, 50f),
  			new PropertySpecification("cLogP", "cLogP", "", "4", 0.5f, 0f, 8f),
  			new PropertySpecification("cLogS", "cLogS", "-4", "", 0.5f, -8f, 2f),
  			new PropertySpecification("tpsa", "Polar surface area", "", "120", 20f, 0f, 250f),
  			new PropertySpecification("donors", "H-Donors", "", "5", 0.5f, 0, 8f),
  			new PropertySpecification("acceptors", "H-Acceptors", "", "10", 1.0f, 0, 16f),
  			new PropertySpecification("flexibility", "Molecular flexibility", "0.3", "0.7", 0.05f, 0f, 1f),
  			new PropertySpecification("complexity", "Molecular complexity", "0.8", "", 0.05f, 0f, 1f),
  			new PropertySpecification("shape", "Molecular shape", "", "0.5", 0.05f, 0f, 1f),
  			new PropertySpecification("rotatableBonds", "Rotatable bond count", "", "4", 5f, 0f, 20f),
  			new PropertySpecification("stereoCenters", "Stereo center count", "1", "3", 2f, 0f, 8f),
  			new PropertySpecification("smallRings", "Ring count (<= 7 atoms)", "2", "", 1f, 0f, 10f),
  			new PropertySpecification("aromaticRings", "Aromatic ring count", "", "2", 1f, 0f, 6f),
  			new PropertySpecification("basicN", "Basic nitrogen count", "1", "", 0.5f, 0f, 6f),
  			new PropertySpecification("acidicO", "Acidic oxygen count", "1", "", 0.5f, 0, 6f),
  			new PropertySpecification("toxicity", "Toxicity Risk", "", "2", 3f, 0, 8f),
  	};
  
  	public static float calculateProperty(StereoMolecule mol, int type) {
  		return (type == MOLECULAR_PROPERTY_MOLWEIGHT) ? mol.getMolweight()
  				: (type == MOLECULAR_PROPERTY_NON_H_ATOMS) ? getNonHAtomCount(mol)
  				: (type == MOLECULAR_PROPERTY_CLOGP) ? new CLogPPredictor().assessCLogP(mol)
  				: (type == MOLECULAR_PROPERTY_CLOGS) ? new SolubilityPredictor().assessSolubility(mol)
  				: (type == MOLECULAR_PROPERTY_TPSA) ? new PolarSurfaceAreaPredictor().assessPSA(mol)
  				: (type == MOLECULAR_PROPERTY_HDONORS) ? getHDonorCount(mol)
  				: (type == MOLECULAR_PROPERTY_HACCEPTORS) ? getHAcceptorCount(mol)
  				: (type == MOLECULAR_PROPERTY_ROTATABLEBONDS) ? mol.getRotatableBondCount()
  				: (type == MOLECULAR_PROPERTY_FLEXIBILITY) ? new MolecularFlexibilityCalculator().calculateMolecularFlexibility(mol)
  				: (type == MOLECULAR_PROPERTY_COMPLEXITY) ? FastMolecularComplexityCalculator.assessComplexity(mol)
  				: (type == MOLECULAR_PROPERTY_SHAPE) ? MolecularShapeCalculator.assessShape(mol)
  				: (type == MOLECULAR_PROPERTY_STEREOCENTERS) ? mol.getStereoCenterCount()
  				: (type == MOLECULAR_PROPERTY_SMALLRINGCOUNT) ? mol.getRingSet().getSize()
  				: (type == MOLECULAR_PROPERTY_AROMRINGCOUNT) ? mol.getAromaticRingCount()
  				: (type == MOLECULAR_PROPERTY_BASIC_NITROGENS) ? getBasicNitrogenCount(mol)
  				: (type == MOLECULAR_PROPERTY_ACIDIC_OXYGENS) ? getAcidicOxygenCount(mol)
  				: (type == MOLECULAR_PROPERTY_TOXICITY_RISK) ? getToxicityRisk(mol)
  				: Float.NaN;
  	}
  
  	public static int getPropertyCount() {
  		return SPEC.length;
  	}
  
  	public static String getPropertyName(int type) {
  		return SPEC[type].name;
  	}
  
  	public static String getPropertyCode(int type) {
  		return SPEC[type].code;
  	}
  
  	public static String getPreferredMin(int type) {
  		return SPEC[type].min;
  	}
  
  	public static String getPreferredMax(int type) {
  		return SPEC[type].max;
  	}
  
  	public static float getRangeMin(int type) {
  		return SPEC[type].rangeMin;
  	}
  
  	public static float getRangeMax(int type) {
  		return SPEC[type].rangeMax;
  	}
  
  	public static double getValuation(double value, double min, double max, double halfWidth) {
  		if (Double.isNaN(value))
  			return Double.NaN;
  
  		double v = 1.0;
  		if (!Double.isNaN(min))
  			v *= 1.0 / (1.0 + Math.exp((min - value) / halfWidth));
  		if (!Double.isNaN(max))
  			v *= 1.0 / (1.0 + Math.exp((value - max) / halfWidth));
  		return v;
  	}
  
  	public static int getTypeFromCode(String code) {
  		for (int i=0; i<SPEC.length; i++)
  			if (SPEC[i].code.equals(code))
  				return i;
  		return -1;
  	}
  
  	public static int getTypeFromName(String name) {
  		for (int i=0; i<SPEC.length; i++)
  			if (SPEC[i].name.equals(name))
  				return i;
  		return -1;
  	}
  
  	public static String getMinText(int type) {
  		return SPEC[type].min;
  	}
  
  	public static String getMaxText(int type) {
  		return SPEC[type].max;
  	}
  
  	public static float getHalfFitnessWidth(int type) {
  		return SPEC[type].halfWidth;
  	}
  
  	private static int getToxicityRisk(StereoMolecule mol) {
  		int result = 0;
  		ToxicityPredictor tp = new ToxicityPredictor();
  		for (int riskType=0; riskType<ToxicityPredictor.cRiskTypes; riskType++) {
  			int risk = tp.assessRisk(mol, riskType, null);
  			if (risk == ToxicityPredictor.cLowRisk)
  				result += 1;
  			else if (risk == ToxicityPredictor.cHighRisk)
  				result += 2;
  			}
  		return result;
  	}
  
  	private static int getNonHAtomCount(StereoMolecule mol) {
  		mol.ensureHelperArrays(Molecule.cHelperNeighbours);
  		return mol.getAtoms();
  	}
  
  	private static int getHAcceptorCount(StereoMolecule mol) {
  		int count = 0;
  		for (int atom = 0; atom < mol.getAllAtoms(); atom++)
  			if (mol.getAtomicNo(atom) == 7 || mol.getAtomicNo(atom) == 8)
  				count++;
  		return count;
  	}
  
  	private static int getHDonorCount(StereoMolecule mol) {
  		int count = 0;
  		for (int atom = 0; atom < mol.getAllAtoms(); atom++)
  			if ((mol.getAtomicNo(atom) == 7 || mol.getAtomicNo(atom) == 8) && mol.getAllHydrogens(atom) > 0)
  				count++;
  		return count;
  	}
  
  	private static int getBasicNitrogenCount(StereoMolecule mol) {
  		int count = 0;
  		mol.ensureHelperArrays(Molecule.cHelperRings);
  		for (int atom=0; atom<mol.getAtoms(); atom++)
  			if (AtomFunctionAnalyzer.isBasicNitrogen(mol, atom))
  				count++;
  		return count;
  	}
  
  	private static int getAcidicOxygenCount(StereoMolecule mol) {
  		int count = 0;
  		mol.ensureHelperArrays(Molecule.cHelperRings);
  		for (int atom=0; atom<mol.getAtoms(); atom++)
  			if (AtomFunctionAnalyzer.isAcidicOxygen(mol, atom))
  				count++;
  		return count;
  	}
  
  }
  
  class PropertySpecification {
  	float halfWidth,rangeMin,rangeMax;	// rangeMin and rangeMax should define a typical range to display the distribution of this property
  	String code,name,min,max;
  
  	public PropertySpecification(String code, String name, String min, String max, float halfWidth, float rangeMin, float rangeMax) {
  		this.code = code;
  		this.name = name;
  		this.min = min;
  		this.max = max;
  		this.halfWidth = halfWidth;
  		this.rangeMin = rangeMin;
  		this.rangeMax = rangeMax;
  	}
  }
  