public void TestCNSPcore()
{
var filename = "NCDK.Data.MDL.cnssmarts.sdf";
var ins = ResourceLoader.GetAsStream(filename);
var reader = new EnumerableSDFReader(ins, CDK.Builder);
var query = new PharmacophoreQuery();
var arom = new PharmacophoreQueryAtom("A", "c1ccccc1");
var n1 = new PharmacophoreQueryAtom("BasicAmine", "[NX3;h2,h1,H1,H2;!$(NC=O)]");
var b1 = new PharmacophoreQueryBond(arom, n1, 5.0, 7.0);
query.Atoms.Add(arom);
query.Atoms.Add(n1);
query.Bonds.Add(b1);
var mol = reader.First();
reader.Close();
var matcher = new PharmacophoreMatcher(query);
var status = matcher.Matches(mol);
Assert.IsTrue(status);
var pmatches = matcher.GetMatchingPharmacophoreAtoms();
Assert.AreEqual(1, pmatches.Count);
var upmatches = matcher.GetUniqueMatchingPharmacophoreAtoms();
Assert.AreEqual(1, upmatches.Count);
}
public void TestAngleMatch2()
{
var filename = "NCDK.Data.MDL.cnssmarts.sdf";
var ins = ResourceLoader.GetAsStream(filename);
var reader = new EnumerableSDFReader(ins, CDK.Builder);
var query = new PharmacophoreQuery();
var n1 = new PharmacophoreQueryAtom("BasicAmine", "[NX3;h2,h1,H1,H2;!$(NC=O)]");
var n2 = new PharmacophoreQueryAtom("BasicAmine", "[NX3;h2,h1,H1,H2;!$(NC=O)]");
var n3 = new PharmacophoreQueryAtom("BasicAmine", "[NX3;h2,h1,H1,H2;!$(NC=O)]");
var b1 = new PharmacophoreQueryAngleBond(n1, n2, n3, 89.14);
query.Atoms.Add(n1);
query.Atoms.Add(n2);
query.Atoms.Add(n3);
query.Bonds.Add(b1);
var mol = reader.First();
reader.Close();
var matcher = new PharmacophoreMatcher(query);
var status = matcher.Matches(mol);
Assert.IsTrue(status);
}
public void TestMatcherQuery1()
{
Assert.IsNotNull(conformers);
// make a query
var query = new PharmacophoreQuery();
var o = new PharmacophoreQueryAtom("D", "[OX1]");
var n1 = new PharmacophoreQueryAtom("A", "[N]");
var n2 = new PharmacophoreQueryAtom("A", "[N]");
query.Atoms.Add(o);
query.Atoms.Add(n1);
query.Atoms.Add(n2);
var b1 = new PharmacophoreQueryBond(o, n1, 4.0, 4.5);
var b2 = new PharmacophoreQueryBond(o, n2, 4.0, 5.0);
var b3 = new PharmacophoreQueryBond(n1, n2, 5.4, 5.8);
query.Bonds.Add(b1);
query.Bonds.Add(b2);
query.Bonds.Add(b3);
var matcher = new PharmacophoreMatcher(query);
bool firstTime = true;
int i = 0;
var statuses = new bool[100];
foreach (var conf in conformers)
{
if (firstTime)
{
statuses[i] = matcher.Matches(conf, true);
firstTime = false;
}
else
{
statuses[i] = matcher.Matches(conf, false);
}
i++;
}
var hits = new int[18];
int idx = 0;
for (i = 0; i < statuses.Length; i++)
{
if (statuses[i])
{
hits[idx++] = i;
}
}
int[] expected = { 0, 1, 2, 5, 6, 7, 8, 9, 10, 20, 23, 48, 62, 64, 66, 70, 76, 87 };
for (i = 0; i < expected.Length; i++)
{
Assert.AreEqual(expected[i], hits[i], $"Hit {i} didn't match");
}
}
/* process a single pcore definition */
private static PharmacophoreQuery ProcessPharmacophoreElement(XElement e, Dictionary <string, string> global)
{
PharmacophoreQuery ret = new PharmacophoreQuery();
ret.SetProperty("description", e.Attribute("description")?.Value);
ret.Title = e.Attribute("name")?.Value;
// first get any local group definitions
Dictionary <string, string> local = GetGroupDefinitions(e);
// now lets look at the constraints
var children = e.Elements();
foreach (var child in children)
{
if (string.Equals(child.Name.LocalName, "distanceConstraint", StringComparison.Ordinal))
{
ProcessDistanceConstraint(child, local, global, ret);
}
else if (string.Equals(child.Name.LocalName, "angleConstraint", StringComparison.Ordinal))
{
ProcessAngleConstraint(child, local, global, ret);
}
}
return(ret);
}
public void TestAngleMatch3()
{
Assert.IsNotNull(conformers);
// make a query
var query = new PharmacophoreQuery();
var o = new PharmacophoreQueryAtom("D", "[OX1]");
var n1 = new PharmacophoreQueryAtom("A", "[N]");
var n2 = new PharmacophoreQueryAtom("A", "[N]");
query.Atoms.Add(o);
query.Atoms.Add(n1);
query.Atoms.Add(n2);
var b1 = new PharmacophoreQueryAngleBond(o, n1, n2, 43, 47);
query.Bonds.Add(b1);
var matcher = new PharmacophoreMatcher(query);
bool firstTime = true;
int i = 0;
var statuses = new bool[100];
foreach (var conf in conformers)
{
if (firstTime)
{
statuses[i] = matcher.Matches(conf, true);
firstTime = false;
}
else
{
statuses[i] = matcher.Matches(conf, false);
}
i++;
}
Assert.AreEqual(100, statuses.Length);
var hits = new int[9];
int idx = 0;
for (i = 0; i < statuses.Length; i++)
{
if (statuses[i])
{
hits[idx++] = i;
}
}
int[] expected = { 0, 6, 32, 33, 48, 54, 60, 62, 69 };
for (i = 0; i < expected.Length; i++)
{
Assert.AreEqual(expected[i], hits[i], $"Hit {i} didn't match");
}
}
private static bool ContainsPatom(PharmacophoreQuery q, string id)
{
foreach (var queryAtom in q.Atoms)
{
if (queryAtom.Symbol.Equals(id, StringComparison.Ordinal))
{
return(true);
}
}
return(false);
}
public void TestMatchedBonds()
{
Assert.IsNotNull(conformers);
// make a query
var query = new PharmacophoreQuery();
var o = new PharmacophoreQueryAtom("D", "[OX1]");
var n1 = new PharmacophoreQueryAtom("A", "[N]");
var n2 = new PharmacophoreQueryAtom("A", "[N]");
query.Atoms.Add(o);
query.Atoms.Add(n1);
query.Atoms.Add(n2);
var b1 = new PharmacophoreQueryBond(o, n1, 4.0, 4.5);
var b2 = new PharmacophoreQueryBond(o, n2, 4.0, 5.0);
var b3 = new PharmacophoreQueryBond(n1, n2, 5.4, 5.8);
query.Bonds.Add(b1);
query.Bonds.Add(b2);
query.Bonds.Add(b3);
var conf1 = conformers[0];
var matcher = new PharmacophoreMatcher(query);
bool status = matcher.Matches(conf1);
Assert.IsTrue(status);
var bMatches = matcher.GetMatchingPharmacophoreBonds();
Assert.AreEqual(2, bMatches.Count); // 2 since we haven't gotten a unique set
Assert.AreEqual(3, bMatches[0].Count);
var pbond = (PharmacophoreBond)BondRef.Deref(bMatches[0][0]);
var patom1 = (PharmacophoreAtom)AtomRef.Deref(pbond.Begin);
var patom2 = (PharmacophoreAtom)AtomRef.Deref(pbond.End);
Assert.AreEqual("D", patom1.Symbol);
Assert.AreEqual("A", patom2.Symbol);
var bondMap = matcher.GetTargetQueryBondMappings();
Assert.AreEqual(2, bondMap.Count);
var mapping = bondMap[0];
// get the 'BondRef' for lookup
var value = mapping[bMatches[0][0]];
Assert.AreEqual(b1, value);
}
public void TestGetterSetter()
{
var query = new PharmacophoreQuery();
var arom = new PharmacophoreQueryAtom("A", "c1ccccc1");
var n1 = new PharmacophoreQueryAtom("BasicAmine", "[NX3;h2,h1,H1,H2;!$(NC=O)]");
var b1 = new PharmacophoreQueryBond(arom, n1, 5.0, 7.0);
query.Atoms.Add(arom);
query.Atoms.Add(n1);
query.Bonds.Add(b1);
var matcher = new PharmacophoreMatcher();
matcher.SetPharmacophoreQuery(query);
var retQuery = matcher.GetPharmacophoreQuery();
Assert.AreEqual(2, retQuery.Atoms.Count);
Assert.AreEqual(1, retQuery.Bonds.Count);
}
public void TestMatchingBonds()
{
var filename = "NCDK.Data.MDL.cnssmarts.sdf";
var ins = ResourceLoader.GetAsStream(filename);
EnumerableSDFReader reader = new EnumerableSDFReader(ins, CDK.Builder);
PharmacophoreQuery query = new PharmacophoreQuery();
PharmacophoreQueryAtom arom = new PharmacophoreQueryAtom("A", "c1ccccc1");
PharmacophoreQueryAtom n1 = new PharmacophoreQueryAtom("BasicAmine", "[NX3;h2,h1,H1,H2;!$(NC=O)]");
PharmacophoreQueryBond b1 = new PharmacophoreQueryBond(arom, n1, 5.0, 7.0);
query.Atoms.Add(arom);
query.Atoms.Add(n1);
query.Bonds.Add(b1);
IAtomContainer mol = (IAtomContainer)reader.First();
reader.Close();
PharmacophoreMatcher matcher = new PharmacophoreMatcher(query);
bool status = matcher.Matches(mol);
Assert.IsTrue(status);
var pmatches = matcher.GetMatchingPharmacophoreAtoms();
Assert.AreEqual(1, pmatches.Count);
var upmatches = matcher.GetUniqueMatchingPharmacophoreAtoms();
Assert.AreEqual(1, upmatches.Count);
var bmatches = matcher.GetMatchingPharmacophoreBonds();
Assert.AreEqual(1, bmatches.Count);
var bmatch = bmatches[0];
Assert.AreEqual(1, bmatch.Count);
PharmacophoreBond pbond = (PharmacophoreBond)BondRef.Deref(bmatch[0]);
Assert.AreEqual(5.63, pbond.BondLength, 0.01);
}
public PharmacophoreQueryTest()
{
query = new PharmacophoreQuery();
PharmacophoreQueryAtom o = new PharmacophoreQueryAtom("D", "[OX1]");
PharmacophoreQueryAtom n1 = new PharmacophoreQueryAtom("A", "[N]");
PharmacophoreQueryAtom n2 = new PharmacophoreQueryAtom("A", "[N]");
query.Atoms.Add(o);
query.Atoms.Add(n1);
query.Atoms.Add(n2);
PharmacophoreQueryBond b1 = new PharmacophoreQueryBond(o, n1, 4.0, 4.5);
PharmacophoreQueryBond b2 = new PharmacophoreQueryBond(o, n2, 4.0, 5.0);
PharmacophoreQueryBond b3 = new PharmacophoreQueryBond(n1, n2, 5.4, 5.8);
query.Bonds.Add(b1);
query.Bonds.Add(b2);
query.Bonds.Add(b3);
}
public void MultiSmartsQuery()
{
var query = new PharmacophoreQuery();
var rings = new PharmacophoreQueryAtom("A", "c1ccccc1|C1CCCC1");
var o1 = new PharmacophoreQueryAtom("Hd", "[OX1]");
var b1 = new PharmacophoreQueryBond(rings, o1, 3.5, 5.8);
query.Atoms.Add(rings);
query.Atoms.Add(o1);
query.Bonds.Add(b1);
var matcher = new PharmacophoreMatcher();
matcher.SetPharmacophoreQuery(query);
var filename = "NCDK.Data.PCore.multismartpcore.sdf";
var ins = ResourceLoader.GetAsStream(filename);
var reader = new EnumerableSDFReader(ins, CDK.Builder);
var enumerator = reader.GetEnumerator();
enumerator.MoveNext();
var mol = enumerator.Current;
Assert.IsTrue(matcher.Matches(mol));
Assert.AreEqual(1, matcher.GetUniqueMatchingPharmacophoreAtoms().Count);
Assert.AreEqual(2, matcher.GetUniqueMatchingPharmacophoreAtoms()[0].Count);
enumerator.MoveNext();
mol = enumerator.Current;
Assert.IsTrue(matcher.Matches(mol));
Assert.AreEqual(2, matcher.GetUniqueMatchingPharmacophoreAtoms().Count);
Assert.AreEqual(2, matcher.GetUniqueMatchingPharmacophoreAtoms()[0].Count);
Assert.AreEqual(2, matcher.GetUniqueMatchingPharmacophoreAtoms()[1].Count);
enumerator.MoveNext();
mol = enumerator.Current;
reader.Close();
Assert.IsFalse(matcher.Matches(mol));
}
public void TestInvalidQuery()
{
var query = new PharmacophoreQuery();
var o = new PharmacophoreQueryAtom("D", "[OX1]");
var n1 = new PharmacophoreQueryAtom("A", "[N]");
var n2 = new PharmacophoreQueryAtom("A", "[NX3]");
query.Atoms.Add(o);
query.Atoms.Add(n1);
query.Atoms.Add(n2);
var b1 = new PharmacophoreQueryBond(o, n1, 4.0, 4.5);
var b2 = new PharmacophoreQueryBond(o, n2, 4.0, 5.0);
var b3 = new PharmacophoreQueryBond(n1, n2, 5.4, 5.8);
query.Bonds.Add(b1);
query.Bonds.Add(b2);
query.Bonds.Add(b3);
var matcher = new PharmacophoreMatcher(query);
matcher.Matches(conformers[0]);
}
public void TestMatchedAtoms()
{
Assert.IsNotNull(conformers);
// make a query
var query = new PharmacophoreQuery();
var o = new PharmacophoreQueryAtom("D", "[OX1]");
var n1 = new PharmacophoreQueryAtom("A", "[N]");
var n2 = new PharmacophoreQueryAtom("A", "[N]");
query.Atoms.Add(o);
query.Atoms.Add(n1);
query.Atoms.Add(n2);
var b1 = new PharmacophoreQueryBond(o, n1, 4.0, 4.5);
var b2 = new PharmacophoreQueryBond(o, n2, 4.0, 5.0);
var b3 = new PharmacophoreQueryBond(n1, n2, 5.4, 5.8);
query.Bonds.Add(b1);
query.Bonds.Add(b2);
query.Bonds.Add(b3);
var conf1 = conformers[0];
var matcher = new PharmacophoreMatcher(query);
bool status = matcher.Matches(conf1);
Assert.IsTrue(status);
var pmatches = matcher.GetMatchingPharmacophoreAtoms();
Assert.AreEqual(2, pmatches.Count);
var upmatches = matcher.GetUniqueMatchingPharmacophoreAtoms();
Assert.AreEqual(1, upmatches.Count);
}
/// <summary>
/// Set a pharmacophore query.
/// </summary>
/// <param name="query">The query</param>
public void SetPharmacophoreQuery(PharmacophoreQuery query)
{
pharmacophoreQuery = query;
}
/// <summary>
/// Initialize the matcher with a query.
/// </summary>
/// <param name="pharmacophoreQuery">The query pharmacophore</param>
/// <seealso cref="PharmacophoreQueryAtom"/>
/// <seealso cref="PharmacophoreQueryBond"/>
public PharmacophoreMatcher(PharmacophoreQuery pharmacophoreQuery)
{
this.pharmacophoreQuery = pharmacophoreQuery;
}
private static void ProcessAngleConstraint(XElement child, Dictionary <string, string> local,
Dictionary <string, string> global, PharmacophoreQuery ret)
{
double lower;
XAttribute tmp;
tmp = child.Attribute("lower");
if (tmp == null)
{
throw new CDKException("Must have a 'lower' attribute");
}
else
{
lower = double.Parse(tmp.Value, NumberFormatInfo.InvariantInfo);
}
// we may not have an upper bound specified
double upper;
tmp = child.Attribute("upper");
if (tmp != null)
{
upper = double.Parse(tmp.Value, NumberFormatInfo.InvariantInfo);
}
else
{
upper = lower;
}
// now get the three groups for this distance
var grouprefs = child.Elements().ToReadOnlyList();
if (grouprefs.Count != 3)
{
throw new CDKException("An angle constraint can only refer to 3 groups.");
}
string id1 = grouprefs[0].Attribute("id")?.Value;
string id2 = grouprefs[1].Attribute("id")?.Value;
string id3 = grouprefs[2].Attribute("id")?.Value;
// see if it's a local def, else get it from the global list
string smarts1, smarts2, smarts3;
if (local.ContainsKey(id1))
{
smarts1 = local[id1];
}
else if (global.ContainsKey(id1))
{
smarts1 = global[id1];
}
else
{
throw new CDKException("Referring to a non-existant group definition");
}
if (local.ContainsKey(id2))
{
smarts2 = local[id2];
}
else if (global.ContainsKey(id2))
{
smarts2 = global[id2];
}
else
{
throw new CDKException("Referring to a non-existant group definition");
}
if (local.ContainsKey(id3))
{
smarts3 = local[id3];
}
else if (global.ContainsKey(id3))
{
smarts3 = global[id3];
}
else
{
throw new CDKException("Referring to a non-existant group definition");
}
// now see if we already have a correpsondiong pcore atom
// else create a new atom
if (!ContainsPatom(ret, id1))
{
PharmacophoreQueryAtom pqa = new PharmacophoreQueryAtom(id1, smarts1);
ret.Atoms.Add(pqa);
}
if (!ContainsPatom(ret, id2))
{
PharmacophoreQueryAtom pqa = new PharmacophoreQueryAtom(id2, smarts2);
ret.Atoms.Add(pqa);
}
if (!ContainsPatom(ret, id3))
{
PharmacophoreQueryAtom pqa = new PharmacophoreQueryAtom(id3, smarts3);
ret.Atoms.Add(pqa);
}
// now add the constraint as a bond
IAtom a1 = null, a2 = null;
IAtom a3 = null;
foreach (var queryAtom in ret.Atoms)
{
if (queryAtom.Symbol.Equals(id1, StringComparison.Ordinal))
{
a1 = queryAtom;
}
if (queryAtom.Symbol.Equals(id2, StringComparison.Ordinal))
{
a2 = queryAtom;
}
if (queryAtom.Symbol.Equals(id3, StringComparison.Ordinal))
{
a3 = queryAtom;
}
}
ret.Bonds.Add(new PharmacophoreQueryAngleBond((PharmacophoreQueryAtom)a1, (PharmacophoreQueryAtom)a2,
(PharmacophoreQueryAtom)a3, lower, upper));
}
/// <summary>
/// Write out one or more pharmacophore queries in the CDK XML format.
/// </summary>
/// <param name="query">The pharmacophore queries</param>
/// <param name="output">The Stream to write to</param>
/// <exception cref="IOException">if there is a problem writing the XML document</exception>
public static void WritePharmacophoreDefinition(PharmacophoreQuery query, Stream output)
{
WritePharmacophoreDefinition(new PharmacophoreQuery[] { query }, output);
}