/**
* Performs the pharmacophore matching.
*
* @param atomContainer The target molecule. Must have 3D coordinates
* @param initializeTarget If <i>true</i>, the target molecule specified in the first argument
* will be analyzed to identify matching pharmacophore groups. If <i>false</i> this is not
* performed. The latter case is only useful when dealing with conformers since for a given
* molecule, all conformers will have the same pharmacophore groups and only the constraints
* will change from one conformer to another.
* @return true is the target molecule contains the query pharmacophore
* @throws org.openscience.cdk.exception.CDKException if the query pharmacophore was not set or
* the query is invalid or if the molecule does not have 3D coordinates
*/
public boolean matches(IAtomContainer atomContainer, boolean initializeTarget)
throws CDKException {
if (!GeometryUtil.has3DCoordinates(atomContainer))
throw new CDKException("Molecule must have 3D coordinates");
if (pharmacophoreQuery == null)
throw new CDKException("Must set the query pharmacophore before matching");
if (!checkQuery(pharmacophoreQuery))
throw new CDKException(
"A problem in the query. Make sure all pharmacophore groups of the same symbol have the same same SMARTS");
String title = (String) atomContainer.getProperty(CDKConstants.TITLE);
if (initializeTarget) pharmacophoreMolecule = getPharmacophoreMolecule(atomContainer);
else {
// even though the atoms comprising the pcore groups are
// constant, their coords will differ, so we need to make
// sure we get the latest set of effective coordinates
for (IAtom iAtom : pharmacophoreMolecule.atoms()) {
PharmacophoreAtom patom = (PharmacophoreAtom) iAtom;
List<Integer> tmpList = new ArrayList<Integer>();
for (int idx : patom.getMatchingAtoms()) tmpList.add(idx);
Point3d coords = getEffectiveCoordinates(atomContainer, tmpList);
patom.setPoint3d(coords);
}
}
if (pharmacophoreMolecule.getAtomCount() < pharmacophoreQuery.getAtomCount()) {
logger.debug("Target [" + title + "] did not match the query SMARTS. Skipping constraints");
return false;
}
mappings = Pattern.findSubstructure(pharmacophoreQuery).matchAll(pharmacophoreMolecule);
// XXX: doing one search then discarding
return mappings.atLeast(1);
}
/**
* Convert the input into a pcore molecule.
*
* @param input the compound being converted from
* @return pcore molecule
* @throws CDKException match failed
*/
private IAtomContainer getPharmacophoreMolecule(IAtomContainer input) throws CDKException {
// XXX: prepare query, to be moved
prepareInput(input);
IAtomContainer pharmacophoreMolecule =
input.getBuilder().newInstance(IAtomContainer.class, 0, 0, 0, 0);
final Set<String> matched = new HashSet<>();
final Set<PharmacophoreAtom> uniqueAtoms = new LinkedHashSet<>();
logger.debug("Converting [" + input.getProperty(CDKConstants.TITLE) + "] to a pcore molecule");
// lets loop over each pcore query atom
for (IAtom atom : pharmacophoreQuery.atoms()) {
final PharmacophoreQueryAtom qatom = (PharmacophoreQueryAtom) atom;
final String smarts = qatom.getSmarts();
// a pcore query might have multiple instances of a given pcore atom (say
// 2 hydrophobic groups separated by X unit). In such a case we want to find
// the atoms matching the pgroup SMARTS just once, rather than redoing the
// matching for each instance of the pcore query atom.
if (!matched.add(qatom.getSymbol())) continue;
// see if the smarts for this pcore query atom gets any matches
// in our query molecule. If so, then collect each set of
// matching atoms and for each set make a new pcore atom and
// add it to the pcore atom container object
int count = 0;
for (final IQueryAtomContainer query : qatom.getCompiledSmarts()) {
// create the lazy mappings iterator
final Mappings mappings = Pattern.findSubstructure(query).matchAll(input).uniqueAtoms();
for (final int[] mapping : mappings) {
uniqueAtoms.add(newPCoreAtom(input, qatom, smarts, mapping));
count++;
}
}
logger.debug("\tFound " + count + " unique matches for " + smarts);
}
pharmacophoreMolecule.setAtoms(uniqueAtoms.toArray(new IAtom[uniqueAtoms.size()]));
// now that we have added all the pcore atoms to the container
// we need to join all atoms with pcore bonds (i.e. distance constraints)
if (hasDistanceConstraints(pharmacophoreQuery)) {
int npatom = pharmacophoreMolecule.getAtomCount();
for (int i = 0; i < npatom - 1; i++) {
for (int j = i + 1; j < npatom; j++) {
PharmacophoreAtom atom1 = (PharmacophoreAtom) pharmacophoreMolecule.getAtom(i);
PharmacophoreAtom atom2 = (PharmacophoreAtom) pharmacophoreMolecule.getAtom(j);
PharmacophoreBond bond = new PharmacophoreBond(atom1, atom2);
pharmacophoreMolecule.addBond(bond);
}
}
}
// if we have angle constraints, generate only the valid
// possible angle relationships, rather than all possible
if (hasAngleConstraints(pharmacophoreQuery)) {
int nangleDefs = 0;
for (IBond bond : pharmacophoreQuery.bonds()) {
if (!(bond instanceof PharmacophoreQueryAngleBond)) continue;
IAtom startQAtom = bond.getAtom(0);
IAtom middleQAtom = bond.getAtom(1);
IAtom endQAtom = bond.getAtom(2);
// make a list of the patoms in the target that match
// each type of angle atom
List<IAtom> startl = new ArrayList<IAtom>();
List<IAtom> middlel = new ArrayList<IAtom>();
List<IAtom> endl = new ArrayList<IAtom>();
for (IAtom tatom : pharmacophoreMolecule.atoms()) {
if (tatom.getSymbol().equals(startQAtom.getSymbol())) startl.add(tatom);
if (tatom.getSymbol().equals(middleQAtom.getSymbol())) middlel.add(tatom);
if (tatom.getSymbol().equals(endQAtom.getSymbol())) endl.add(tatom);
}
// now we form the relevant angles, but we will
// have reversed repeats
List<IAtom[]> tmpl = new ArrayList<IAtom[]>();
for (IAtom middle : middlel) {
for (IAtom start : startl) {
if (middle.equals(start)) continue;
for (IAtom end : endl) {
if (start.equals(end) || middle.equals(end)) continue;
tmpl.add(new IAtom[] {start, middle, end});
}
}
}
// now clean up reversed repeats
List<IAtom[]> unique = new ArrayList<IAtom[]>();
for (int i = 0; i < tmpl.size(); i++) {
IAtom[] seq1 = tmpl.get(i);
boolean isRepeat = false;
for (int j = 0; j < unique.size(); j++) {
if (i == j) continue;
IAtom[] seq2 = unique.get(j);
if (seq1[1] == seq2[1] && seq1[0] == seq2[2] && seq1[2] == seq2[0]) {
isRepeat = true;
}
}
if (!isRepeat) unique.add(seq1);
}
// finally we can add the unique angle to the target
for (IAtom[] seq : unique) {
PharmacophoreAngleBond pbond =
new PharmacophoreAngleBond(
(PharmacophoreAtom) seq[0],
(PharmacophoreAtom) seq[1],
(PharmacophoreAtom) seq[2]);
pharmacophoreMolecule.addBond(pbond);
nangleDefs++;
}
}
logger.debug("Added " + nangleDefs + " defs to the target pcore molecule");
}
return pharmacophoreMolecule;
}
