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.
   *
   * @author Thomas Sander
   */
  
  package com.actelion.research.chem.prediction;
  
  import com.actelion.research.chem.Molecule;
  import com.actelion.research.chem.StereoMolecule;
  
  /*
  Description: Every non-hydrogen atom is associated with an atom type from a list of about 63 distinct atom types.
  20 of these atoms types are considered contributing to non-polar surface and the rest contributes to the molecule's
  polar surface area. An atom type looks like '[CH2](-*)-*', which is a carbon atom connected to 2 hydrogen atoms
  and to two other atoms of any kind. Atom types are not only associated with polar or non-polar surfaces,
  they also have a numerical value describing the extent of which they are contributing to that kind of surface.
  For instance any atom belonging to the CH2-atom type above adds 13.76 square Angstrom to the non-polar surface of a molecule.
  After determining all atom's types, their contributions to the polar and the non-polar surface of the molecule
  are added up. Then the relative polar surface area is calculated as the total of the polar surface devided by
  the sum of polar and non-polar surface.
   */
  public class TotalSurfaceAreaPredictor extends PolarSurfaceAreaPredictor {
  	public static final float cPSAUnknown = -1.0f;
  
  	public static final String[] cNonPolarAtomTypeName = {
  		"[B](-*)(-*)-*",
  		"[BH2]-*",
  		"[B-](-*)(-*)(-*)-*",
  		"[C](-*)(-*)(-*)-*",
  		"[C](-*)(-*)=*",
  		"[C](=*)=*",
  		"[C](-*)#*",
  		"[CH](-*)(-*)-*",
  		"[CH](-*)=*",
  		"[CH]#*",
  		"[CH2](-*)-*",
  		"[CH2]=*",
  		"[CH3]-*",
  		"[c](:*)(:*):*",
  		"[c](-*)(:*):*",
  		"[cH](:*):*",
  		"[F]-*",
  		"[Cl]-*",
  		"[Br]-*",
  		"[I]-*",
  		};
  
  	/* These are the increments from Actelion3D surface calculation (VdW radii, 1.4A probe),
  	 * which creates somewhat smaller values than the Schroedinger method.
  	 * The average error of the PLS prediction (ChEMBL training set) was about 7 square angstrom. */
  	private static final float[] cPolarIncrement = {
  		 3.55f, 11.51f, 13.56f,  4.34f, 25.88f,  1.55f, 11.46f, 21.62f, 15.60f, 15.27f,
  		-7.62f, -5.20f, 17.76f, 17.59f,  0.00f,  7.74f, -1.15f, 14.48f, 10.97f,  7.95f,
  		 6.87f,  1.22f, 13.99f,-18.78f,  2.76f,  0.00f, 10.00f, 17.65f, 13.04f, 13.10f,
  		14.28f, 14.11f, 17.49f, 28.00f,  9.68f,  2.50f, 22.61f, 20.36f,  0.00f,  0.00f,
  		 0.00f,  3.98f,  8.45f }; 
  
  	private static final float[] cNonPolarIncrement = {
  		 7.85f, 20.62f,  0.04f, -3.09f,  4.71f, 12.52f, 14.90f,  5.75f, 13.25f, 15.66f,
  		13.76f, 18.04f, 19.01f,  5.09f,  5.46f, 12.21f, 13.10f, 22.17f, 25.38f, 33.03f };
  
  	/* These are the increments approximating the Schroedinger method (VdW radii, 1.4A probe).
  	 * The average error of the PLS prediction (ChEMBL training set) was about 10 square angstrom.
  	private static final float[] cPolarIncrement = {
  		 3.96f, 12.12f,  7.11f,  3.65f, 18.40f, -0.46f, 12.34f, 18.64f, 13.41f, 13.51f,
  	   -10.84f, -0.86f,  1.55f,  6.00f,  0.00f,  2.10f,  0.10f, 17.22f, 10.85f,  7.53f,
  	     6.85f,  0.72f, 13.09f, -0.20f,  4.69f,  0.00f, 10.40f, 16.13f, 11.87f, 12.49f,
  	    11.65f, 13.61f, 14.99f, 24.11f,  7.06f,  1.74f, 20.31f, 17.97f,  0.00f,  0.00f,
  	     0.00f,  4.48f,  5.87f };
  
  	private static final float[] cNonPolarIncrement = {
  		 3.11f, -0.00f, -2.45f, -3.22f,  5.06f, 10.02f, 16.42f,  5.82f, 14.71f, 13.37f,
  		15.93f, 17.64f, 20.61f,  6.15f,  6.78f, 12.69f, 11.75f, 17.60f, 21.76f, 28.12f }; 
  	*/
  
  	public TotalSurfaceAreaPredictor() {
  		}
  
  	public static int getNonPolarAtomTypeCount() {
  		return cNonPolarAtomTypeName.length;
  		}
  
  	/**
  	 * Calculates the topological total surface area (TPSA) of a molecule as a sum of
  	 * contributions of its polar and non-atom-types. This method the contributions of all polar
  	 * atoms. Contributions of polar and non-polar atom types were calculated as follows:
  	 * 92879 unique reliable active structures with molecular weights between 200 and 700
  	 * were selected from the ChEMBL_20 database. For every structure one conformer was
  	 * generated and minimized by the MMFF94 forcefield. Total surface areas were calculated
  	 * as solvent accessible surface using Van der Waals radii and a probe of 1.4 angstrom
  	 * radius. Surface contribution values were for 43 polar and 20 non polar atom types were
  	 * calculated as a multi-linear regression with a PLS approach.
  	 * 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 topological total surface area estimated from atom type specific increments
  	 */
  	public float assessTotalSurfaceArea(StereoMolecule mol) {
  		return assessNonPolarSurfaceArea(mol) + assessPolarSurfaceArea(mol);
  		}
  
  	/**
  	 * Calculates the topological polar surface area (TPSA) of a molecule as a sum of
  	 * contributions of its polar atom-types. This method the contributions of all polar
  	 * atoms. Contributions of polar and non-polar atom types were calculated as follows:
  	 * 92879 unique reliable active structures with molecular weights between 200 and 700
  	 * were selected from the ChEMBL_20 database. For every structure one conformer was
  	 * generated and minimized by the MMFF94 forcefield. Total surface areas were calculated
  	 * as solvent accessible surface using Van der Waals radii and a probe of 1.4 angstrom
  	 * radius. Surface contribution values were for 43 polar and 20 non polar atom types were
  	 * calculated as a multi-linear regression with a PLS approach.
  	 * 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 topological polar surface area estimated from atom type specific increments
  	 */
  	public float assessPolarSurfaceArea(StereoMolecule mol) {
  		int[] count = getPolarAtomTypeCounts(mol);
  
  		float psa = 0.0f;
  		for (int i=0; i<cPolarIncrement.length; i++)
  			psa += count[i] * cPolarIncrement[i];
  
  		return psa;
  		}
  
  	/**
  	 * Calculates the topological non-polar surface area (TPSA) of a molecule as a sum of
  	 * contributions of its non-polar atom-types. This method the contributions of all polar
  	 * atoms. Contributions of polar and non-polar atom types were calculated as follows:
  	 * 92879 unique reliable active structures with molecular weights between 200 and 700
  	 * were selected from the ChEMBL_20 database. For every structure one conformer was
  	 * generated and minimized by the MMFF94 forcefield. Total surface areas were calculated
  	 * as solvent accessible surface using Van der Waals radii and a probe of 1.4 angstrom
  	 * radius. Surface contribution values were for 43 polar and 20 non polar atom types were
  	 * calculated as a multi-linear regression with a PLS approach.
  	 * 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 topological non-polar surface area estimated from atom type specific increments
  	 */
  	public float assessNonPolarSurfaceArea(StereoMolecule mol) {
  		int[] count = getNonPolarAtomTypeCounts(mol);
  
  		float npsa = 0.0f;
  		for (int i=0; i<cNonPolarIncrement.length; i++)
  			npsa += count[i] * cNonPolarIncrement[i];
  
  		return npsa;
  		}
  
  	/**
  	 * Calculates the relative (fractional) polar surface area from polar and non-polar atom
  	 * contributions. This method does not use the Peter Ertl increments.
  	 * 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 topological relative surface area estimated from atom type specific increments
  	 */
  	public float assessRelativePolarSurfaceArea(StereoMolecule mol) {
  		float psa = assessPolarSurfaceArea(mol);
  		float npsa = assessNonPolarSurfaceArea(mol);
  		return psa / (psa + npsa);
  		}
  
  	public ParameterizedStringList getDetail(StereoMolecule mol) {
  		ParameterizedStringList detail = new ParameterizedStringList();
  		detail.add("The total surface area prediction is based on an atom-type based",
  							ParameterizedStringList.cStringTypeText);
  		detail.add("increment system. Recognized atom types and their contributions are:",
  							ParameterizedStringList.cStringTypeText);
  
  		addNonPolarAtomTypeIncrements(mol, detail);
  		addPolarAtomTypeIncrements(mol, detail);
  
  		return detail;
  		}
  
  	private void addPolarAtomTypeIncrements(StereoMolecule mol, ParameterizedStringList detail) {
  		int[] count = getPolarAtomTypeCounts(mol);
  
  		for (int i=0; i<cPolarIncrement.length; i++)
  			if (count[i] != 0)
  				detail.add(""+count[i]+" * "+cPolarIncrement[i]+"   AtomType: "
  								  +cPolarAtomTypeName[i],ParameterizedStringList.cStringTypeText);
  		}
  
  	private void addNonPolarAtomTypeIncrements(StereoMolecule mol, ParameterizedStringList detail) {
  		int[] count = getNonPolarAtomTypeCounts(mol);
  
  		for (int i=0; i<cNonPolarIncrement.length; i++)
  			if (count[i] != 0)
  				detail.add(""+count[i]+" * "+cNonPolarIncrement[i]+"   AtomType: "
  								  +cNonPolarAtomTypeName[i],ParameterizedStringList.cStringTypeText);
  		}
  
  	public int[] getNonPolarAtomTypeCounts(StereoMolecule mol) {
  		int[] count = new int[cNonPolarIncrement.length+2];
  
  		mol.ensureHelperArrays(Molecule.cHelperRings);
  
  		for (int atom=0; atom<mol.getAtoms(); atom++)
  			count[getNonPolarAtomType(mol, atom)]++;
  
  		return count;
  		}
  
  	private int getNonPolarAtomType(StereoMolecule mol, int atom) {
  		switch (mol.getAtomicNo(atom)) {
  		case 5:
  			if (mol.getConnAtoms(atom) == 3
  			 && mol.getAtomCharge(atom) == 0
  			 && mol.getAtomPi(atom) == 0)
  				return 0;
  			if (mol.getConnAtoms(atom) == 1
  			 && mol.getAtomCharge(atom) == 0
  			 && mol.getAtomPi(atom) == 0)
  				return 1;
  			if (mol.getConnAtoms(atom) == 4
  			 && mol.getAtomCharge(atom) == -1
  			 && mol.getAtomPi(atom) == 0)
  				return 2;
  			return cNonPolarIncrement.length+1;	// unrecognized B
  		case 6:
  			if (mol.isAromaticAtom(atom)) {
  				if (mol.getAllHydrogens(atom) != 0)
  					return 15;
  				for (int i=0; i<mol.getConnAtoms(atom); i++)
  					if (!mol.isAromaticBond(mol.getConnBond(atom, i)))
  						return 14;
  				return 13;
  				}
  			else {
  				if (mol.getAtomCharge(atom) == 0) {
  					switch (mol.getAllHydrogens(atom)) {
  					case 0:	// hydrogens
  						switch (mol.getAtomPi(atom)) {
  						case 0:	// pi
  							return 3;
  						case 1:	// pi
  							return 4;
  						case 2:	// pi
  							if (mol.getConnBondOrder(atom, 0) == 2)
  								return 5;
  							else
  								return 6;
  							}
  						break;
  					case 1:	// hydrogens
  						switch (mol.getAtomPi(atom)) {
  						case 0:	// pi
  							return 7;
  						case 1:	// pi
  							return 8;
  						case 2:	// pi
  							return 9;
  							}
  						break;
  					case 2:	// hydrogens
  						switch (mol.getAtomPi(atom)) {
  						case 0:	// pi
  							return 10;
  						case 1:	// pi
  							return 11;
  							}
  					case 3:	// hydrogens
  						return 12;
  						}
  					}
  				}
  			return cNonPolarIncrement.length+1;	// unrecognized C
  		case 9:	// F
  			return 16;
  		case 17:	// Cl
  			return 17;
  		case 35:	// Br
  			return 18;
  		case 53:	// I
  			return 19;
  		default:
  			return cNonPolarIncrement.length;	// undefined type
  			}
  		}
  	}
  