/// <summary>
/// Performs the pharmacophore matching.
/// </summary>
/// <param name="atomContainer">The target molecule. Must have 3D coordinates</param>
/// <param name="initializeTarget">If <see langword="true"/>, the target molecule specified in the
/// first argument will be analyzed to identify matching pharmacophore groups. If <see langword="false"/>
/// 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.</param>
/// <returns><see langword="true"/> is the target molecule contains the query pharmacophore</returns>
/// <exception cref="CDKException">
/// if the query pharmacophore was not set or the query is invalid or if the molecule
/// does not have 3D coordinates</exception>
public bool Matches(IAtomContainer atomContainer, bool initializeTarget)
{
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");
}
var title = atomContainer.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
foreach (var iAtom in pharmacophoreMolecule.Atoms)
{
var patom = PharmacophoreAtom.Get(iAtom);
var tmpList = new List <int>();
foreach (var idx in patom.GetMatchingAtoms())
{
tmpList.Add(idx);
}
var coords = GetEffectiveCoordinates(atomContainer, tmpList);
patom.Point3D = coords;
}
}
if (pharmacophoreMolecule.Atoms.Count < pharmacophoreQuery.Atoms.Count)
{
Debug.WriteLine($"Target [{title}] did not match the query SMARTS. Skipping constraints");
return(false);
}
mappings = Pattern.FindSubstructure(pharmacophoreQuery).MatchAll(pharmacophoreMolecule);
// XXX: doing one search then discarding
return(mappings.AtLeast(1));
}
/// <summary>
/// Checks whether this query atom matches a target atom.
/// <para>
/// Currently a query pharmacophore atom will match a target pharmacophore group if the
/// symbols of the two groups match. This is based on the assumption that
/// pharmacophore groups with the same symbol will have the same SMARTS
/// pattern.
/// </para>
/// </summary>
/// <param name="atom">A target pharmacophore group</param>
/// <returns>true if the current query group has the same symbol as the target group</returns>
public bool Matches(IAtom atom)
{
var patom = PharmacophoreAtom.Get(atom);
return(patom.Symbol.Equals(Symbol, StringComparison.Ordinal));
}
/// <summary>
/// Convert the input into a pcore molecule.
/// </summary>
/// <param name="input">the compound being converted from</param>
/// <returns>pcore molecule </returns>
/// <exception cref="CDKException">match failed</exception>
private IAtomContainer GetPharmacophoreMolecule(IAtomContainer input)
{
// XXX: prepare query, to be moved
PrepareInput(input);
var pharmacophoreMolecule = input.Builder.NewAtomContainer();
var matched = new HashSet <string>();
var uniqueAtoms = new LinkedHashSet <PharmacophoreAtom>();
Debug.WriteLine($"Converting [{input.Title}] to a pcore molecule");
// lets loop over each pcore query atom
foreach (var atom in pharmacophoreQuery.Atoms)
{
var qatom = (PharmacophoreQueryAtom)atom;
var smarts = qatom.Smarts;
// 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.Symbol))
{
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;
foreach (var query in qatom.CompiledSmarts)
{
// create the lazy mappings iterator
var mappings = query.MatchAll(input).GetUniqueAtoms();
foreach (var mapping in mappings)
{
uniqueAtoms.Add(NewPCoreAtom(input, qatom, smarts, mapping));
count++;
}
}
Debug.WriteLine($"\tFound {count} unique matches for {smarts}");
}
pharmacophoreMolecule.SetAtoms(uniqueAtoms.ToArray());
// 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))
{
var npatom = pharmacophoreMolecule.Atoms.Count;
for (int i = 0; i < npatom - 1; i++)
{
for (int j = i + 1; j < npatom; j++)
{
var atom1 = PharmacophoreAtom.Get(pharmacophoreMolecule.Atoms[i]);
var atom2 = PharmacophoreAtom.Get(pharmacophoreMolecule.Atoms[j]);
var bond = new PharmacophoreBond(atom1, atom2);
pharmacophoreMolecule.Bonds.Add(bond);
}
}
}
// if we have angle constraints, generate only the valid
// possible angle relationships, rather than all possible
if (HasAngleConstraints(pharmacophoreQuery))
{
int nangleDefs = 0;
foreach (var bond in pharmacophoreQuery.Bonds)
{
if (!(bond is PharmacophoreQueryAngleBond))
{
continue;
}
var startQAtom = bond.Atoms[0];
var middleQAtom = bond.Atoms[1];
var endQAtom = bond.Atoms[2];
// make a list of the patoms in the target that match
// each type of angle atom
var startl = new List <IAtom>();
var middlel = new List <IAtom>();
var endl = new List <IAtom>();
foreach (var tatom in pharmacophoreMolecule.Atoms)
{
if (tatom.Symbol.Equals(startQAtom.Symbol, StringComparison.Ordinal))
{
startl.Add(tatom);
}
if (tatom.Symbol.Equals(middleQAtom.Symbol, StringComparison.Ordinal))
{
middlel.Add(tatom);
}
if (tatom.Symbol.Equals(endQAtom.Symbol, StringComparison.Ordinal))
{
endl.Add(tatom);
}
}
// now we form the relevant angles, but we will
// have reversed repeats
var tmpl = new List <IAtom[]>();
foreach (var middle in middlel)
{
foreach (var start in startl)
{
if (middle.Equals(start))
{
continue;
}
foreach (var end in endl)
{
if (start.Equals(end) || middle.Equals(end))
{
continue;
}
tmpl.Add(new IAtom[] { start, middle, end });
}
}
}
// now clean up reversed repeats
var unique = new List <IAtom[]>();
for (int i = 0; i < tmpl.Count; i++)
{
var seq1 = tmpl[i];
bool isRepeat = false;
for (int j = 0; j < unique.Count; j++)
{
if (i == j)
{
continue;
}
var seq2 = unique[j];
if (Compares.AreDeepEqual(seq1[1], seq2[1]) && Compares.AreDeepEqual(seq1[0], seq2[2]) && Compares.AreDeepEqual(seq1[2], seq2[0]))
{
isRepeat = true;
}
}
if (!isRepeat)
{
unique.Add(seq1);
}
}
// finally we can add the unique angle to the target
foreach (var seq in unique)
{
var pbond = new PharmacophoreAngleBond(PharmacophoreAtom.Get(seq[0]), PharmacophoreAtom.Get(seq[1]), PharmacophoreAtom.Get(seq[2]));
pharmacophoreMolecule.Bonds.Add(pbond);
nangleDefs++;
}
}
Debug.WriteLine($"Added {nangleDefs} defs to the target pcore molecule");
}
return(pharmacophoreMolecule);
}
