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Open Source Chemistry Library
package com.actelion.research.chem.phesa;
import com.actelion.research.calc.ThreadMaster;
import com.actelion.research.chem.*;
import com.actelion.research.chem.alignment3d.PheSAAlignmentOptimizer;
import com.actelion.research.chem.alignment3d.PheSAAlignmentOptimizer.PheSASetting;
import com.actelion.research.chem.alignment3d.transformation.Rotation;
import com.actelion.research.chem.alignment3d.transformation.Transformation;
import com.actelion.research.chem.alignment3d.transformation.TransformationSequence;
import com.actelion.research.chem.alignment3d.transformation.Translation;
import com.actelion.research.chem.conf.Conformer;
import com.actelion.research.chem.conf.ConformerSet;
import com.actelion.research.chem.conf.ConformerSetGenerator;
import com.actelion.research.chem.descriptor.DescriptorConstants;
import com.actelion.research.chem.descriptor.DescriptorHandler;
import com.actelion.research.chem.descriptor.DescriptorInfo;
import com.actelion.research.chem.phesaflex.FlexibleShapeAlignment;
import java.nio.charset.StandardCharsets;
import java.util.ArrayList;
import java.util.List;
/**
* @version: 1.0, February 2018
* Author: JW
* a molecular shape descriptor is a shape-ensemble (molecular shapes of generated conformers of a molecule)
* it also contains information about the atom-connectivity,elements,... so for any molecular shape, the corresponding
* molecule can be reconstructed
* there are different modi for calculating the shape similarity:
* 0: only takes into account molecule shape for alignment and overlap calculation
* 1: alignment solely based on shape, but overlap calculation incorporates pharmacophore overlaps
* 2: both alignment and overlap calculation take a combined score of shape and pharmacophore overlap
* 3: only the pharmacophore overlap is used for both aligment and overlap calculation -> this is the fastest method!
* 19 April 2018: performance enhancement by using a cutoff for the calculation of atom-atom overlaps and preculated exp-values with linear interpolation
* TODO: add Tversky index
* July 2019: various improvements in the Code, moved to DD_core
*/
public class DescriptorHandlerShape implements DescriptorHandler {
private static final int CONFORMATIONS = 200;
public static final int SIZE_CUTOFF = 200;
private static DescriptorHandlerShape INSTANCE;
public static final PheSAMolecule FAILED_OBJECT = new PheSAMolecule();
private boolean singleBaseConformation; // take conformation of base molecule as is and don't generate conformers
private List preProcessTransformations;
private StereoMolecule[] previousAlignment;// = new StereoMolecule[2];
private double[] previousPhesaResult;
private PheSASetting phesaSetting;
protected int maxConfs;
protected double ppWeight;
protected boolean flexible;
protected ThreadMaster threadMaster;
// Maximum number of tries to generate conformers with the torsion rule based conformer generator from Thomas Sander
private ConformerSetGenerator conformerGenerator;
public DescriptorHandlerShape() {
this(false,CONFORMATIONS,0.5);
}
public DescriptorHandlerShape(boolean useSingleBaseConformation) {
this(useSingleBaseConformation,CONFORMATIONS,0.5);
}
public DescriptorHandlerShape(boolean useSingleBaseConformation, double ppWeight) {
this(useSingleBaseConformation,CONFORMATIONS,ppWeight);
}
public DescriptorHandlerShape(int maxConfs,double ppWeight) {
this(false,maxConfs,ppWeight);
}
/**
*
* @param ppWeight similarity weight for the pharmacophore in total similarity.
*/
public DescriptorHandlerShape(double ppWeight) {
this(false,CONFORMATIONS,ppWeight);
}
public DescriptorHandlerShape(boolean useSingleBaseConformation,int maxConfs, double ppWeight) {
flexible = false;
singleBaseConformation = useSingleBaseConformation;
this.maxConfs = maxConfs;
this.ppWeight = ppWeight;
init();
conformerGenerator = new ConformerSetGenerator(maxConfs);
conformerGenerator.setThreadMaster(threadMaster);
preProcessTransformations = new ArrayList<>();
phesaSetting = new PheSASetting();
}
public PheSASetting getPhesaSetting() {
return phesaSetting;
}
public void setPhesaSetting(PheSASetting phesaSetting) {
this.phesaSetting = phesaSetting;
}
public void setThreadMaster(ThreadMaster tm) {
this.threadMaster = tm;
}
public List getPreProcessTransformations() {
return preProcessTransformations;
}
public PheSAMolecule createDescriptor(ConformerSet confSet) {
preProcessTransformations = new ArrayList<>();
try {
init();
ArrayList molecularVolumes = new ArrayList();
StereoMolecule mol = confSet.first().toMolecule();
if(mol.getAtoms()>SIZE_CUTOFF)
return FAILED_OBJECT;
MolecularVolume refMolVol = new MolecularVolume(mol);
MolecularVolume molVol;
for(Conformer conformer : confSet) {
if(conformer==null) {
break;
} else {
molVol = new MolecularVolume(refMolVol,conformer);
Coordinates com = molVol.getCOM();
Rotation rotation = molVol.preProcess(conformer);
TransformationSequence transformation = new TransformationSequence();
transformation.addTransformation(rotation.getInvert());
transformation.addTransformation(new Translation(new double[] {com.x,com.y,com.z}));
preProcessTransformations.add(transformation);
molecularVolumes.add(molVol);
}
}
mol = confSet.first().toMolecule();
return new PheSAMolecule(mol,molecularVolumes);
}
catch(Exception e) {
return FAILED_OBJECT;
}
}
public void init() {
previousAlignment = new StereoMolecule[2];
}
/**
* the ShapeDescriptor consists of a whole ensemble of MolecularVolumes (MolecularGaussians),
* obtained from a conformational search algorithm
*/
public PheSAMolecule createDescriptor(StereoMolecule mol) {
StereoMolecule shapeMolecule = new StereoMolecule(mol);
shapeMolecule.ensureHelperArrays(StereoMolecule.cHelperCIP);
boolean has3Dcoordinates = false;
for (int atom=1; atom 0.1) {
has3Dcoordinates = true;
break;
}
}
shapeMolecule.stripSmallFragments();
Canonizer can = new Canonizer(shapeMolecule);
shapeMolecule = can.getCanMolecule(true);
ConformerSet confSet = new ConformerSet();
if (!singleBaseConformation) {
confSet = conformerGenerator.generateConformerSet(shapeMolecule);
}
else if(!has3Dcoordinates) {
return FAILED_OBJECT;
}
else {
if(shapeMolecule.getAllAtoms()-shapeMolecule.getAtoms()==0) {
System.err.println("missing hydrogens in 3D structure");
return FAILED_OBJECT;
}
confSet.add(new Conformer(shapeMolecule)); //take input conformation
}
return this.createDescriptor(confSet);
}
/**
* calculates the Shape- and/or Pharmacophore similarity of a query molecule with a base molecule
*
*/
public float getSimilarity(PheSAMolecule query, PheSAMolecule base) {
StereoMolecule[] bestPair = {query.getMolecule(),base.getMolecule()};
double[] result = PheSAAlignmentOptimizer.align(query,base,bestPair,phesaSetting);
this.setPreviousAlignment(bestPair);
this.setPreviousPheSAResult(result);
if(flexible) {
FlexibleShapeAlignment fsa = new FlexibleShapeAlignment(bestPair[0],bestPair[1]);
fsa.setSettings(phesaSetting);
result = fsa.align();
this.setPreviousPheSAResult(result);
}
return (float)result[0];
}
public StereoMolecule[] getPreviousAlignment() {
return this.previousAlignment;
}
/***
* additional output:
* element 0: total similarity (identical to getSimilarity(...))
* element 1: pharmacophore similarity
* element 2: contribution to similarity that originates from additional volumes (incl/excl)
* @return
*/
public double[] getPreviousPheSAResult() {
return this.previousPhesaResult;
}
public void setPreviousAlignment(StereoMolecule[] previousAlignment) {
this.previousAlignment = previousAlignment;
}
public void setPreviousPheSAResult(double[] previousPhesaResult) {
this.previousPhesaResult = previousPhesaResult;
}
public String getVersion() {
return DescriptorConstants.DESCRIPTOR_ShapeAlign.version;
}
public DescriptorInfo getInfo() {
return DescriptorConstants.DESCRIPTOR_ShapeAlign;
}
public String encode(PheSAMolecule o) {
if(calculationFailed(o)){
return FAILED_STRING;
}
ArrayList molVols = null;
PheSAMolecule shapeMol;
if(o instanceof PheSAMolecule){
shapeMol = (PheSAMolecule)o;
molVols = shapeMol.getVolumes();
} else {
return FAILED_STRING;
}
StringBuilder shapeString = new StringBuilder();
int nrOfMolVols = molVols.size();
shapeString.append(Integer.toString(nrOfMolVols));
shapeString.append(" ");
shapeString.append(molVols.get(0).encodeFull());
shapeString.append(" ");
for(int i=1;i molVols = new ArrayList();
int nrOfMolVols = Integer.decode(splitted[0]);
MolecularVolume refMolVol = MolecularVolume.decodeFull(splitted[1], mol);
molVols.add(refMolVol);
for(int i=2;i