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Additional stereo wedge checks and corner cases. We need to check the… #839

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Feb 12, 2022
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Additional stereo wedge checks and corner cases. We need to check the… #839

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106 changes: 91 additions & 15 deletions base/standard/src/main/java/org/openscience/cdk/stereo/StereoElementFactory.java
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Original file line number Diff line number Diff line change
Expand Up @@ -96,7 +96,7 @@ public abstract class StereoElementFactory {
/** A bond map for fast access to bond labels between two atom indices. */
protected final EdgeToBondMap bondMap;


protected final Set<Projection> projections = EnumSet.noneOf(Projection.class);

protected boolean strict;
Expand Down Expand Up @@ -460,14 +460,14 @@ abstract ExtendedCisTrans createExtendedCisTrans(List<IBond> bonds,

/**
* Indicate that stereochemistry drawn as a certain projection should be
* interpreted.
* interpreted.
*
* <pre>{@code
* StereoElementFactory factory =
* StereoElementFactory factory =
* StereoElementFactory.using2DCoordinates(container)
* .interpretProjections(Projection.Fischer, Projection.Haworth);
* }</pre>
*
*
* @param projections types of projection
* @return self
* @see org.openscience.cdk.stereo.Projection
Expand Down Expand Up @@ -661,19 +661,69 @@ private boolean isOkay(int a, int b) {
// check some obvious stereo chemistry errors, see the InChI
// technical manual "Definition of 2D drawing correctness"
private boolean verifyWedgePattern(IAtom focus, int n, List<IBond> bonds) {
bonds.sort(GeometryUtil.polarBondComparator(focus));
if (n == 3) {
// no sort needed
int ref = 0;
for (IBond bond : bonds) {
int curr = elevationOf(focus, bond);
if (!isOkay(ref, curr)) {
logger.error("Badly drawn stereochemistry with 3 neighbours, up/down bonds should not be mixed!");
return false;
} else
ref = curr;
double angle = getMaxSweep(focus, bonds);
double delta = angle - Math.PI;
double threshold = 0.01;
// largest angle between 2 neighbours is > 180 => wedges should
// alternate
if (delta > threshold) {
int ref = 0;
for (IBond bond : bonds) {
int curr = elevationOf(focus, bond);
if (!isOkay(ref, curr)) {
logger.error("Invalid wedge pattern, up/down bonds should be mixed when there is an acute angle!");
return false;
} else
ref = curr;
ref = -ref;
}
}
// larges angle between 2 neighbours is < 180 => all wedges
// should be the same
else if (delta < -threshold) {
int ref = 0;
for (IBond bond : bonds) {
int curr = elevationOf(focus, bond);
if (!isOkay(ref, curr)) {
logger.error("Invalid wedge pattern, up/down bonds should be same when there is not an acute angle!");
return false;
} else
ref = curr;
}
} else {
// 180-degrees, check where the wedge is
if (bonds.size() != 3)
throw new IllegalArgumentException("3 bonds only!");
Vector2d v1 = toUnitVector(focus, bonds.get(0).getOther(focus));
Vector2d v2 = toUnitVector(focus, bonds.get(1).getOther(focus));
Vector2d v3 = toUnitVector(focus, bonds.get(2).getOther(focus));
String ambiuousStereoMesg = "Ambiguous stereochemistry - 3 neighbours and two";
if (Math.abs(signedAngle(v1,v2) - Math.PI) < threshold) {
if (elevationOf(focus, bonds.get(0)) == 0 &&
elevationOf(focus, bonds.get(1)) == 0 &&
elevationOf(focus, bonds.get(2)) != 0) {
logger.error(ambiuousStereoMesg);
return false;
}
} else if (Math.abs(signedAngle(v2,v3) - Math.PI) < threshold) {
if (elevationOf(focus, bonds.get(0)) != 0 &&
elevationOf(focus, bonds.get(1)) == 0 &&
elevationOf(focus, bonds.get(2)) == 0) {
logger.error(ambiuousStereoMesg);
return false;
}
} else if (Math.abs(signedAngle(v3,v1) - Math.PI) < threshold) {
if (elevationOf(focus, bonds.get(0)) == 0 &&
elevationOf(focus, bonds.get(1)) != 0 &&
elevationOf(focus, bonds.get(2)) == 0) {
logger.error(ambiuousStereoMesg);
return false;
}
}
}
} else { // n == 4
bonds.sort(GeometryUtil.polarBondComparator(focus));
int ref = 0;
for (IBond bond : bonds) {
int curr = elevationOf(focus, bond);
Expand All @@ -692,6 +742,26 @@ private boolean verifyWedgePattern(IAtom focus, int n, List<IBond> bonds) {
return true;
}

private double signedAngle(Vector2d a, Vector2d b) {
double angle = Math.atan2(a.x*b.y-a.y*b.x, a.x*b.x+a.y*b.y);
return angle >= 0 ? (2*Math.PI)-angle : -angle;
}

private double max(double a, double b, double c) {
return Math.max(a, Math.max(b, c));
}

private double getMaxSweep(IAtom atom, List<IBond> bonds) {
if (bonds.size() != 3)
throw new IllegalArgumentException("3 bonds only!");
Vector2d v1 = toUnitVector(atom, bonds.get(0).getOther(atom));
Vector2d v2 = toUnitVector(atom, bonds.get(1).getOther(atom));
Vector2d v3 = toUnitVector(atom, bonds.get(2).getOther(atom));
return max(signedAngle(v1, v2),
signedAngle(v2, v3),
signedAngle(v3, v1));
}

private static boolean isWedged(IBond bond) {
switch (bond.getStereo()) {
case UP:
Expand Down Expand Up @@ -1049,6 +1119,12 @@ private Point2d toUnitVector(Point2d from, Point2d to) {
return new Point2d(v2d);
}

private Vector2d toUnitVector(IAtom from, IAtom to) {
if (from.equals(to))
return new Vector2d(0, 0);
return new Vector2d(toUnitVector(from.getPoint2d(), to.getPoint2d()));
}

/**
* Compute the signed volume of the tetrahedron from the planar points
* and elevations.
Expand Down Expand Up @@ -1292,7 +1368,7 @@ ExtendedTetrahedral createExtendedTetrahedral(int v, Stereocenters stereocenters
IAtom focus = container.getAtom(v);

if (hasUnspecifiedParity(focus)) return null;

if (container.getConnectedBondsCount(focus) != 2)
return null;

Expand Down
79 changes: 76 additions & 3 deletions base/test-standard/src/test/java/org/openscience/cdk/stereo/StereoElementFactoryTest.java
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Original file line number Diff line number Diff line change
Expand Up @@ -35,6 +35,7 @@
import org.openscience.cdk.interfaces.IStereoElement;
import org.openscience.cdk.interfaces.ITetrahedralChirality;
import org.openscience.cdk.io.MDLV2000Reader;
import org.openscience.cdk.io.MDLV2000Writer;
import org.openscience.cdk.silent.Atom;
import org.openscience.cdk.silent.AtomContainer;
import org.openscience.cdk.silent.SilentChemObjectBuilder;
Expand Down Expand Up @@ -626,11 +627,10 @@ public void badWedgePatternWithThreeNeighbors() throws CDKException {
m.addBond(1, 0, IBond.Order.SINGLE, IBond.Stereo.DOWN); // CH-OH
m.addBond(1, 2, IBond.Order.SINGLE, IBond.Stereo.UP); // CH-CH2
m.addBond(1, 3, IBond.Order.SINGLE); // CH-Cl

StereoElementFactory factory = StereoElementFactory.using2DCoordinates(m);
Assert.assertNotNull(factory.createTetrahedral(m.getAtom(1), Stereocenters.of(m)));
factory.withStrictMode();
Assert.assertNull(factory.createTetrahedral(m.getAtom(1), Stereocenters.of(m)));
Assert.assertNull(factory.createTetrahedral(m.getAtom(0), Stereocenters.of(m)));
}

@Test
Expand All @@ -650,10 +650,83 @@ public void okWedgePatternWithThreeNeighbors() throws CDKException {
Assert.assertNotNull(factory.createTetrahedral(m.getAtom(1), Stereocenters.of(m)));
}

// see http://efficientbits.blogspot.com/2019/09/rules-for-interpreting-updown-wedge.html
@Test
public void okWedgePatternWithThreeNeighbors2() throws Exception {
IChemObjectBuilder builder = SilentChemObjectBuilder.getInstance();
try (InputStream in = getClass().getResourceAsStream("wedge_okay_d3.mol");
MDLV2000Reader mdlr = new MDLV2000Reader(in)) {
mdlr.getSetting("AddStereoElements").setSetting("false");
IAtomContainer mol = mdlr.read(builder.newAtomContainer());
int numStereo = 0;
for (IStereoElement<?,?> se : mol.stereoElements())
numStereo++;
assertEquals(0, numStereo);
StereoElementFactory stereoFactory = StereoElementFactory.using2DCoordinates(mol);
Assert.assertEquals(1, stereoFactory.createAll().size());
stereoFactory.withStrictMode();
Assert.assertEquals(1, stereoFactory.createAll().size());
}
}

@Test
public void badWedgePatternWithThreeNeighbors2() throws Exception {
IChemObjectBuilder builder = SilentChemObjectBuilder.getInstance();
try (InputStream in = getClass().getResourceAsStream("wedge_bad_d3.mol");
MDLV2000Reader mdlr = new MDLV2000Reader(in)) {
mdlr.getSetting("AddStereoElements").setSetting("false");
IAtomContainer mol = mdlr.read(builder.newAtomContainer());
int numStereo = 0;
for (IStereoElement<?,?> se : mol.stereoElements())
numStereo++;
assertEquals(0, numStereo);
StereoElementFactory stereoFactory = StereoElementFactory.using2DCoordinates(mol);
Assert.assertEquals(1, stereoFactory.createAll().size());
stereoFactory.withStrictMode();
Assert.assertEquals(0, stereoFactory.createAll().size());
}
}

@Test
public void badWedgePatternWithThreeNeighbors180() throws Exception {
IChemObjectBuilder builder = SilentChemObjectBuilder.getInstance();
try (InputStream in = getClass().getResourceAsStream("wedge_180_bad_d3.mol");
MDLV2000Reader mdlr = new MDLV2000Reader(in)) {
mdlr.getSetting("AddStereoElements").setSetting("false");
IAtomContainer mol = mdlr.read(builder.newAtomContainer());
int numStereo = 0;
for (IStereoElement<?,?> se : mol.stereoElements())
numStereo++;
assertEquals(0, numStereo);
StereoElementFactory stereoFactory = StereoElementFactory.using2DCoordinates(mol);
Assert.assertEquals(1, stereoFactory.createAll().size());
stereoFactory.withStrictMode();
Assert.assertEquals(0, stereoFactory.createAll().size());
}
}

@Test
public void okWedgePatternWithThreeNeighbors180() throws Exception {
IChemObjectBuilder builder = SilentChemObjectBuilder.getInstance();
try (InputStream in = getClass().getResourceAsStream("wedge_180_okay_d3.mol");
MDLV2000Reader mdlr = new MDLV2000Reader(in)) {
mdlr.getSetting("AddStereoElements").setSetting("false");
IAtomContainer mol = mdlr.read(builder.newAtomContainer());
int numStereo = 0;
for (IStereoElement<?,?> se : mol.stereoElements())
numStereo++;
assertEquals(0, numStereo);
StereoElementFactory stereoFactory = StereoElementFactory.using2DCoordinates(mol);
Assert.assertEquals(1, stereoFactory.createAll().size());
stereoFactory.withStrictMode();
Assert.assertEquals(1, stereoFactory.createAll().size());
}
}

@Test
public void badWedgePatternWithFourNeighbors() throws Exception {
IChemObjectBuilder builder = SilentChemObjectBuilder.getInstance();
try (InputStream in = getClass().getResourceAsStream("bad-wedges-4nbors.mol");
try (InputStream in = getClass().getResourceAsStream("wedge_bad_d4.mol");
MDLV2000Reader mdlr = new MDLV2000Reader(in)) {
mdlr.getSetting("AddStereoElements").setSetting("false");
IAtomContainer mol = mdlr.read(builder.newAtomContainer());
Expand Down
12 changes: 12 additions & 0 deletions base/test-standard/src/test/resources/org/openscience/cdk/stereo/wedge_180_bad_d3.mol
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@@ -0,0 +1,12 @@

ChemDraw02112215352D

4 3 0 0 0 0 0 0 0 0999 V2000
-0.8250 0.4094 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.0000 0.4115 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.8250 0.4135 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
0.0021 -0.4135 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0
2 3 1 0
2 4 1 1
M END
12 changes: 12 additions & 0 deletions base/test-standard/src/test/resources/org/openscience/cdk/stereo/wedge_180_okay_d3.mol
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@@ -0,0 +1,12 @@

ChemDraw02112216072D

4 3 0 0 1 0 0 0 0 0999 V2000
-0.8250 0.4094 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.0000 0.4115 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.8250 0.4135 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
0.0021 -0.4135 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0
2 3 1 1
2 4 1 0
M END
12 changes: 12 additions & 0 deletions base/test-standard/src/test/resources/org/openscience/cdk/stereo/wedge_bad_d3.mol
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ChemDraw02112215332D

4 3 0 0 1 0 0 0 0 0999 V2000
-0.7145 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.0000 0.4125 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.7145 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
0.0000 -0.4125 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0
2 3 1 1
2 4 1 1
M END
0 ...nscience/cdk/stereo/bad-wedges-4nbors.mol → ...g/openscience/cdk/stereo/wedge_bad_d4.mol
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12 changes: 12 additions & 0 deletions base/test-standard/src/test/resources/org/openscience/cdk/stereo/wedge_okay_d3.mol
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ChemDraw02112215322D

4 3 0 0 1 0 0 0 0 0999 V2000
-0.7145 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.0000 0.4125 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.7145 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
0.0000 -0.4125 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0
2 3 1 6
2 4 1 1
M END