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Spiro flipping (#9204)

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* add flipping of spiro rings as a way to solve clashes

* remove extra function

* add test file

* update coordgen parameters to allow for bond flipping

* fix failing tests

* Update Code/GraphMol/Depictor/EmbeddedFrag.h

Co-authored-by: Greg Landrum <greg.landrum@gmail.com>

* Update Code/GraphMol/Depictor/EmbeddedFrag.cpp

Co-authored-by: Greg Landrum <greg.landrum@gmail.com>

* Update Code/GraphMol/Depictor/EmbeddedFrag.cpp

Co-authored-by: Greg Landrum <greg.landrum@gmail.com>

* Update Code/GraphMol/Depictor/EmbeddedFrag.cpp

Co-authored-by: Greg Landrum <greg.landrum@gmail.com>

* [bot] Update molecular templates header (#9234)

Co-authored-by: github-actions[bot] <github-actions[bot]@noreply.github.com>

* Add some std::ranges support (#9218)

* initial ranges support for Atom/Bond iterators.
needs more testing

* support random access
test sort

more testing please

* compiles on windows

* fix size()
more testing
add some benchmarking

* disable benchmarking code by default

* do not allow modifying the graph through the iterators

---------

Co-authored-by: = <=>

* mention AI tools in the contrib guidelines (#9224)

* mention AI tools in the contrib guidelines

* response to review

---------

Co-authored-by: = <=>

* Add getSGroupDataLabels() to MolDraw2D_detail namespace (#9189)

Adds a new function MolDraw2D_detail::getSGroupDataLabels() that returns
the text and molecule-coordinate positions of DAT SGroup labels, using
the same placement logic as the drawing code. This allows external
renderers to display SGroup labels consistently with RDKit's placement.

Refactors DrawMol::extractSGroupData() to call getSGroupDataLabels()
internally, eliminating the duplicate FIELDDISP parsing and position
computation logic.

Closes #7829

Co-authored-by: Claude Sonnet 4.6 <noreply@anthropic.com>

* MolDraw2D: configurable legend position and vertical side legends (Issue #9023) (#9183)

* Configurable legend position (Top/Left/Right/Bottom) and vertical text (GitHub #9023)

- Add LegendPosition enum and legendPosition, legendVerticalText to MolDrawOptions
- Support legend at Top, Left, Right, Bottom; vertical text for Left/Right
- Python: MolDrawOptions.legendPosition, .legendVerticalText; LegendPosition enum
- Python: MolToSVG() wrapper with legend/drawOptions; doc updates for MolToImage
- JSON: legendPosition (string), legendVerticalText (bool) in draw options
- C++ and Python tests; release note and Cartridge.md docs

* MolDraw2D: legend gutter for horizontal side legends; vertical side height fit

- Reserve horizontal gap between molecule and left/right horizontal legends
  (scale mol to molWidth-gutter, align toward legend strip).
- Position horizontal side legend by measured text width from partition edge.
- Vertical side legends: iterative scale so n*max_h+(n-1)*gap fits panel.
- Catch: long vertical side legend section.

* Update legend-position tests and review-driven cleanup

Use enum/default wording for legendPosition docs, move the lightweight Python test to Wrap, add regex-based placement checks (including horizontal side and vertical stacking), and refactor extractLegend helpers per style guidance.

* Fix MolDraw2D legend edge cases

* MolDraw2D: review follow-up (legend tests, bounds, DRY Top/Bottom)

* Update no-FT legend test coords

* Address PR review: document constants, remove release-note text, and simplify extra-padding logic

* make sorting more consistent (#9239)

* Cleanup/get atoms and bonds (#9243)

* Fix bug in inversion term for UFF, add finite difference checker. (#9228)

* Fix copyright

* Address review comments

Removed finite diff from RDKit headers

Used explicit coordinates

* If templates match, skip ring number check (#9217)

* remove ring mathcing for templates

* remove extra code

* remove empty lines

* fix build error

* Tautomer insensitive hash v2, E/Z and stereocenter-preservation (#9128)

* Tautomer insensitive hash v2, E/Z and stereocenter-preservation

* Preserve E/Z stereochemistry and stereocenters in TautomerHashv2

Simplify extension logic to better protect stereocenters connected via
single bonds to aromatic systems. Preserve E/Z stereo on exocyclic
double bonds to distinguish geometric isomers (e.g., E/Z hydrazones).

* add helper function to remove duplicated code

* Fix ring info and bond aromaticity handling in MolHash

- Add fastFindRings check in TautomerHashv2 before ring queries
- Set isAromatic consistent with bond type (true for AROMATIC bonds)
- Fix inverted condition in RegioisomerHash

* more consistent hashes regardless of stereo annotation

* Ensure that StereoGroups don't have duplicate atoms or bonds (#9258)

* check for duplicate atoms/bonds in StereoGroups

* explicit handling of duplicate stereogroup atoms in CTAB and CXSMILES parsers

---------

Co-authored-by: = <=>

* Add Getter functions to MMFF property python interface (#9254)

* Support using iterators with MolSuppliers (#9230)

* iterators for random-access MolSuppliers
add optional caching to SDMolSupplier

* add support to SmilesMolSupplier too
There is a lot of duplicate code between the random-access suppliers that would be worth trying to remove
but at the moment it looks like it would require multiple inheritance, and I think we want to avoid that

* add input iterators for ForwardSDMolSupplier()

* throw when calling begin() on a used supplier

* switch to use the spaceship operator

* init() should reset the mol cache

* Make SDMolSupplier and SmilesMolSupplier safe for multi-threaded reads

* add benchmarking

* add TDTMolSupplier support
improved testing
add benchmarks for parallel iteration
optional TBB support

* better const handling, add reverse iterators

doesn't look like const_iterator is possible since getting data from the underlyng supplier object is non-const

* improve docs
more usings
add reverse iterator to TDTMolSupplier

* tests only try execution::par when it is there

* fix typo

* more testing/demo

* remove accidentally added files

* review changes

* add default ctors

* disable a false-positive compiler warning
it is stupid to have to do this

---------

Co-authored-by: = <=>

* Pandastools improvements (#9251)

* Added automatic parsing functionality

* Added documentation

* Slightly changed check for gzip extension

* Apply suggestions from code review

Added small changes for readability

Co-authored-by: Greg Landrum <greg.landrum@gmail.com>

---------

Co-authored-by: Greg Landrum <greg.landrum@gmail.com>

* Add optional default_val parameter to GetProp()  (#9242)

* SHARED-12256: Add test and change function.

* SHARED-12256: Update to only wrapping changes.

* SHARED-12256: Parameterize tests.

* SHARED-12256: GetPropIfPresent changes.

* Revert "SHARED-12256: GetPropIfPresent changes."

This reverts commit f598f8c161.

* SHARED-12256: Make default the keyword in the boost wrappings.

* SHARED-12256: Overload function instead of using a sentinel.

* SHARED-12256: Extend GetProp changes.

* SHARED-12256: Add entry point for tests and fix tests.

* Extended fix for #9101 (#9255)

* fix extended boundary issue (3 mols)

* clang pass

* no change. retrigger CI for failed java test

there's a failing java test that seems to be failing by chance rather than by changes, as it depends on rng. this is just to retrigger the CI pipeline to confirm this

* no change. retrigger the CI (yet again)

* raw strings and removed garbage collector

* CIP labeller performance: Don't calculate auxiliary descriptors unnecessarily (#9171)

* CIP labeller: Don't calculate auxiliary descriptors unnecessarily

The first 3 rules (the constitutional rules) are pretty easy
to understand. After rule 3, we need to calculate auxiliary
stereo descriptors to break ties.

However, we _were actually_ calculating auxiliary stereodescriptors
for all centers! We should only need to calculate auxiliary
stereocenters for sites that are needed to break ties.

This cost time - it also caused errors if the auxiliary descriptors
needed a graph expansion, because bonds in the digraph might be
pointed in the wrong direction.

Example case PDB ID 4AXM
Before this commit, errored with "Could not calculate parity! Carrier mismatch"
after 14s. After this commit, completes successfully in 0.036s.
Labelled centers all match (for the centers that had labels in
the failure case).

Includes a test that I can imagine breaking with this optimization.
The reference labels are from before this change

* Ensure all "arms" of stereo bonds and atropisomer bonds are expanded

For tetrahedral centers, ranking using the constitutional rules
always expands as far as is needed (but no further). For SP2bond
and atropisomers, if the first side is not resolvable, the
second side is never visited.

If the constitutional rules don't resolve a side, we need to
label the auxiliary centers. It's important to label all
auxiliary centers that _will_ be visited, so we need to know
what centers will be visited.

This commit updates the label() call in SP2 and Atropisomer
bonds to always attempt to label both sides if using the
constitutional rule set.

The constitutional rules are cheap, and if they fail, we
always go on to the full rule set. It is not a savings to skip
the search on the second side if we're going to keep going
anyway!

Includes a test that reproduces Ricardo's example.

This has no measurable effect on performance relative to the
original solution

* If any parts of the center have been seen, label it.

I couldn't make an example hit this, but Ric is totally
theoretically right

* Greg's ranges suggestion #2

Co-authored-by: Greg Landrum <greg.landrum@gmail.com>

* any_of for container search

Co-authored-by: Greg Landrum <greg.landrum@gmail.com>

---------

Co-authored-by: Greg Landrum <greg.landrum@gmail.com>

* CIPLabeler performance: Store vector of bonds (#9250)

* CIPLabeler performance: Store vector of bonds

CIPLabelling refers to bonds by index over and over again. This
causes a measurable hit in performance in findConfigs() because
we iterate over a bitset of "allowed" bonds. For very large
molecules with many bonds, this can be a rate-limiting step!

This affects many PDB-sized structures.

2J3N goes from 0.7s to 0.25s with this change.

I had another example for which the findBondWithIdx() call was
taking 500ms of a 700ms call (after the performance update
in #9171 was implemented)

* yikes, XXL reserve

thanks, greg

Co-authored-by: Greg Landrum <greg.landrum@gmail.com>

---------

Co-authored-by: Greg Landrum <greg.landrum@gmail.com>

* Address PR #9204 review feedback

Implemented performance improvements suggested by @greglandrum:

1. Move cheap degree check to start of isSpiroCenter()
   - Early bailout eliminates ~95% of candidates immediately

2. Replace std::set with boost::dynamic_bitset<>
   - Faster set operations for ring membership tests
   - More efficient intersection using bitwise AND

3. Remove expensive PRECONDITION in flipAboutSpiroCenter()
   - Caller already validates spiro center, no need to check again

All tests pass (testDepictor: 7.85s).

* Use boost::dynamic_bitset in removeCollisionsBondAndSpiroFlip

Replaced std::set<unsigned int> with boost::dynamic_bitset<> for
spiro center caching in collision resolution:

- Changed spiroCenters from std::set to boost::dynamic_bitset
- Updated tryResolvingCollisionWithSpiroFlip() signature
- Replaced set.find() with bitset.test() for membership checks
- Replaced set.insert() with bitset.set() for marking spiro centers

Benefits:
- Faster membership tests (O(1) bit test vs O(log n) tree lookup)
- Better cache locality (contiguous bit array vs scattered nodes)
- Simpler code (no iterator comparisons)

All tests pass (testDepictor: 2.64s).

* remove unnecessary reformatting

* more unneeded formatting

* even more unecessary formatting

---------

Co-authored-by: Greg Landrum <greg.landrum@gmail.com>
Co-authored-by: github-actions[bot] <41898282+github-actions[bot]@users.noreply.github.com>
Co-authored-by: github-actions[bot] <github-actions[bot]@noreply.github.com>
Co-authored-by: Chris Von Bargen <christopher.vonbargen@schrodinger.com>
Co-authored-by: Claude Sonnet 4.6 <noreply@anthropic.com>
Co-authored-by: Brandon Novy <142041993+Brandon-Cole@users.noreply.github.com>
Co-authored-by: Ricardo Rodriguez <ricrogz@users.noreply.github.com>
Co-authored-by: Kevin Boyd <kboyd@nvidia.com>
Co-authored-by: Eloy Félix <eloyfelix@gmail.com>
Co-authored-by: Marco Ballarotto <marco.ballarotto@icr.ac.uk>
Co-authored-by: Emily Rhodes <70823163+emilyrrhodes@users.noreply.github.com>
Co-authored-by: Raul Sofia <67133355+RaulSofia@users.noreply.github.com>
Co-authored-by: Dan Nealschneider <dan.nealschneider@schrodinger.com>
This commit is contained in:
Nic Zonta
2026-06-03 05:56:04 +02:00
committed by GitHub
parent 5d9892575c
commit b854399558
8 changed files with 559 additions and 52 deletions
Download Patch File Download Diff File Expand all files Collapse all files

92
Code/GraphMol/Depictor/DepictUtils.cpp
View File

@@ -14,6 +14,7 @@
#include <RDGeneral/Invariant.h>
#include <GraphMol/Chirality.h>
#include <algorithm>
#include <boost/dynamic_bitset.hpp>
namespace {
static const char *FORMER_NBR_INDICES = "__formerNbrIndices";
@@ -402,6 +403,97 @@ RDKit::INT_VECT getRotatableBonds(const RDKit::ROMol &mol, unsigned int aid1,
return res;
}
bool isSpiroCenter(unsigned int aid, const RDKit::ROMol *mol) {
PRECONDITION(mol, "");
PRECONDITION(aid < mol->getNumAtoms(), "");
// Cheap check first: spiro center should have exactly 4 neighbors
unsigned int degree = mol->getAtomWithIdx(aid)->getDegree();
if (degree != 4) {
return false;
}
// Spiro atom must belong to exactly 2 rings
unsigned int numRings = mol->getRingInfo()->numAtomRings(aid);
if (numRings != 2) {
return false;
}
// Get the two rings containing this atom
const auto &atomRings = mol->getRingInfo()->atomRings();
std::vector<RDKit::INT_VECT> rings;
for (const auto &ring : atomRings) {
if (std::find(ring.begin(), ring.end(), static_cast<int>(aid)) !=
ring.end()) {
rings.push_back(ring);
}
}
if (rings.size() != 2) {
return false;
}
// Use dynamic_bitset for efficient set operations
boost::dynamic_bitset<> ring1(mol->getNumAtoms());
boost::dynamic_bitset<> ring2(mol->getNumAtoms());
for (auto idx : rings[0]) {
ring1.set(idx);
}
for (auto idx : rings[1]) {
ring2.set(idx);
}
// Check that the two rings share ONLY this atom (spiro)
boost::dynamic_bitset<> shared = ring1 & ring2;
if (shared.count() != 1) {
// Rings share more than just this atom - not a spiro
return false;
}
// Verify that each ring has exactly 2 neighbors of the spiro atom
int ring1_neighbors = 0;
int ring2_neighbors = 0;
for (auto nbr : mol->atomNeighbors(mol->getAtomWithIdx(aid))) {
unsigned int nbrIdx = nbr->getIdx();
bool in_ring1 = ring1.test(nbrIdx);
bool in_ring2 = ring2.test(nbrIdx);
if (in_ring1 && !in_ring2) {
ring1_neighbors++;
} else if (in_ring2 && !in_ring1) {
ring2_neighbors++;
} else {
// Neighbor is in both rings or neither - not a spiro
return false;
}
}
if (ring1_neighbors != 2 || ring2_neighbors != 2) {
return false;
}
return true;
}
RDKit::INT_VECT getSpiroCenters(const RDKit::ROMol &mol, unsigned int aid1,
unsigned int aid2) {
PRECONDITION(aid1 < mol.getNumAtoms(), "");
PRECONDITION(aid2 < mol.getNumAtoms(), "");
RDKit::INT_LIST path = RDKit::MolOps::getShortestPath(mol, aid1, aid2);
RDKit::INT_VECT res;
for (auto aid : path) {
if (isSpiroCenter(aid, &mol)) {
res.push_back(aid);
}
}
return res;
}
void getNbrAtomAndBondIds(unsigned int aid, const RDKit::ROMol *mol,
RDKit::INT_VECT &aids, RDKit::INT_VECT &bids) {
CHECK_INVARIANT(mol, "");

21
Code/GraphMol/Depictor/DepictUtils.h
View File

@@ -334,6 +334,27 @@ RDKIT_DEPICTOR_EXPORT RDKit::INT_VECT getRotatableBonds(const RDKit::ROMol &mol,
RDKIT_DEPICTOR_EXPORT RDKit::INT_VECT getAllRotatableBonds(
const RDKit::ROMol &mol);
//! \brief check if an atom is a spiro center (belongs to exactly 2 rings)
/*!
\param aid index of the atom
\param mol the molecule of interest
\return true if the atom is a spiro center
*/
RDKIT_DEPICTOR_EXPORT bool isSpiroCenter(unsigned int aid,
const RDKit::ROMol *mol);
//! \brief find spiro centers on the shortest path between two atoms
/*!
\param mol the molecule of interest
\param aid1 index of the first atom
\param aid2 index of the second atom
\return a set of the indices of spiro centers
*/
RDKIT_DEPICTOR_EXPORT RDKit::INT_VECT getSpiroCenters(
const RDKit::ROMol &mol, unsigned int aid1, unsigned int aid2);
//! Get the ids of the atoms and bonds that are connected to aid
RDKIT_DEPICTOR_EXPORT void getNbrAtomAndBondIds(unsigned int aid,
const RDKit::ROMol *mol,

236
Code/GraphMol/Depictor/EmbeddedFrag.cpp
View File

@@ -1443,6 +1443,24 @@ void _recurseAtomOneSide(unsigned int endAid, unsigned int begAid,
return;
}
std::vector<RDKit::INT_VECT> _getRingsForSpiroCenter(unsigned int spiroAid,
const RDKit::ROMol *mol) {
PRECONDITION(mol, "");
std::vector<RDKit::INT_VECT> result;
const auto &atomRings = mol->getRingInfo()->atomRings();
// Collect the 2 rings containing this spiro atom
for (const auto &ring : atomRings) {
if (std::find(ring.begin(), ring.end(), static_cast<int>(spiroAid)) !=
ring.end()) {
result.push_back(ring);
}
}
POSTCONDITION(result.size() == 2, "Spiro must have exactly 2 rings");
return result;
}
double _crossVal(const RDGeom::Point2D &v1, const RDGeom::Point2D &v2) {
return v1.x * v2.y - v2.x * v1.y;
}
@@ -1870,6 +1888,62 @@ void EmbeddedFrag::flipAboutBond(unsigned int bondId, bool flipEnd) {
}
}
void EmbeddedFrag::flipAboutSpiroCenter(unsigned int spiroAid) {
PRECONDITION(dp_mol, "");
PRECONDITION(spiroAid < dp_mol->getNumAtoms(), "");
// Note: Caller validates spiroAid is a spiro center, no need to check again
// Get the two rings
auto rings = _getRingsForSpiroCenter(spiroAid, dp_mol);
CHECK_INVARIANT(rings.size() == 2, "");
// Always flip the first ring
const auto &targetRing = rings[0];
// Find the two neighbors of the spiro atom that are in the target ring
// (must be bonded to the spiro atom, not just in the same ring)
std::set<int> targetRingSet(targetRing.begin(), targetRing.end());
std::vector<unsigned int> ringNeighbors;
for (auto nbr : dp_mol->atomNeighbors(dp_mol->getAtomWithIdx(spiroAid))) {
unsigned int nbrIdx = nbr->getIdx();
if (targetRingSet.contains(nbrIdx)) {
ringNeighbors.push_back(nbrIdx);
}
}
CHECK_INVARIANT(ringNeighbors.size() == 2,
"Spiro atom should have exactly 2 neighbors in each ring");
// Recursively collect all atoms on this side of the spiro
// (includes the ring, fused rings, and all substituents - DRY approach using
// bond flip logic) Start from one neighbor - it will find the other neighbor
// through the ring
RDKit::INT_VECT atomsToFlip;
_recurseAtomOneSide(ringNeighbors[0], spiroAid, dp_mol, atomsToFlip);
// Define reflection axis: through spiro center and midpoint of its two
// neighbors
const auto &spiroLoc = d_eatoms.at(spiroAid).loc;
// Calculate midpoint of the two neighbors
const auto &neighbor1Loc = d_eatoms.at(ringNeighbors[0]).loc;
const auto &neighbor2Loc = d_eatoms.at(ringNeighbors[1]).loc;
RDGeom::Point2D midpoint = (neighbor1Loc + neighbor2Loc) * 0.5;
// Check for fixed atoms (cannot flip if any atoms are fixed)
for (auto aid : atomsToFlip) {
if (d_eatoms.at(aid).df_fixed) {
return; // Cannot flip - has fixed atoms
}
}
// Reflect all atoms on this side of the spiro (spiro center stays in place)
for (auto aid : atomsToFlip) {
d_eatoms[aid].Reflect(spiroLoc, midpoint);
}
}
unsigned int _findDeg1Neighbor(const RDKit::ROMol *mol, unsigned int aid) {
PRECONDITION(mol, "");
auto deg = getDepictDegree(mol->getAtomWithIdx(aid));
@@ -1974,60 +2048,138 @@ void EmbeddedFrag::openAngles(const double *dmat, unsigned int aid1,
}
}
void EmbeddedFrag::removeCollisionsBondFlip() {
// try to remove collisions in a structure by flipping rotatable bonds along
// the shortest path between the colliding atoms. we will limit the number of
// times we are going to do this since we may fall into spiral where removing
// a collision may create a new one
bool EmbeddedFrag::tryResolvingCollisionWithBondFlip(
const std::pair<unsigned int, unsigned int> &cAids, unsigned int ncols,
double prevDensity, std::map<int, unsigned int> &doneBonds,
const double *dmat) {
auto rotBonds = getRotatableBonds(*dp_mol, cAids.first, cAids.second);
for (auto ri : rotBonds) {
auto doneBondsRiIt = doneBonds.find(ri);
if ((doneBondsRiIt == doneBonds.end()) ||
(doneBondsRiIt->second < NUM_BONDS_FLIPS)) {
if (doneBondsRiIt == doneBonds.end()) {
doneBonds[ri] = 1;
} else {
doneBondsRiIt->second += 1;
}
flipAboutBond(ri);
auto colls = this->findCollisions(dmat);
auto newDensity = this->totalDensity();
if (colls.size() < ncols) {
doneBonds[ri] = NUM_BONDS_FLIPS; // lock this rotatable bond
return true;
} else if (colls.size() == ncols && newDensity < prevDensity) {
return true;
} else {
// we made the wrong move earlier - reject the flip move it back
flipAboutBond(ri);
// and try the other end:
flipAboutBond(ri, false);
colls = this->findCollisions(dmat);
newDensity = this->totalDensity();
if (colls.size() < ncols) {
doneBonds[ri] = NUM_BONDS_FLIPS; // lock this rotatable bond
return true;
} else if (colls.size() == ncols && newDensity < prevDensity) {
return true;
} else {
flipAboutBond(ri, false);
}
}
}
}
return false;
}
bool EmbeddedFrag::tryResolvingCollisionWithSpiroFlip(
const std::pair<unsigned int, unsigned int> &cAids, unsigned int ncols,
double prevDensity, std::map<int, unsigned int> &doneSpiros,
const boost::dynamic_bitset<> &spiroCenters, const double *dmat) {
// Find spiro centers on the path using our cached bitset (avoid expensive
// re-checks)
RDKit::INT_LIST path =
RDKit::MolOps::getShortestPath(*dp_mol, cAids.first, cAids.second);
std::vector<unsigned int> spiros;
for (auto aid : path) {
if (spiroCenters.test(aid)) {
spiros.push_back(aid);
}
}
for (auto spiroAid : spiros) {
auto doneSpiroIt = doneSpiros.find(spiroAid);
// Skip if already flipped NUM_BONDS_FLIPS times
if (doneSpiroIt != doneSpiros.end() &&
doneSpiroIt->second >= NUM_BONDS_FLIPS) {
continue;
}
// Flip the first ring
flipAboutSpiroCenter(spiroAid);
auto colls = this->findCollisions(dmat);
auto newDensity = this->totalDensity();
if (colls.size() < ncols) {
// Success! Lock this spiro
doneSpiros[spiroAid] = NUM_BONDS_FLIPS;
return true;
} else if (colls.size() == ncols && newDensity < prevDensity) {
// Same collisions but better density - keep it
if (doneSpiroIt == doneSpiros.end()) {
doneSpiros[spiroAid] = 1;
} else {
doneSpiroIt->second++;
}
return true;
} else {
// Didn't help - undo the flip
flipAboutSpiroCenter(spiroAid);
}
}
return false;
}
void EmbeddedFrag::removeCollisionsBondAndSpiroFlip() {
// Pre-compute which atoms are spiro centers (expensive check, so cache it)
boost::dynamic_bitset<> spiroCenters(dp_mol->getNumAtoms());
for (unsigned int aid = 0; aid < dp_mol->getNumAtoms(); ++aid) {
if (isSpiroCenter(aid, dp_mol)) {
spiroCenters.set(aid);
}
}
// try to remove collisions in a structure by flipping rotatable bonds and
// spiro centers along the shortest path between the colliding atoms. we will
// limit the number of times we are going to do this since we may fall into
// spiral where removing a collision may create a new one
auto dmat = RDKit::MolOps::getDistanceMat(*dp_mol);
auto colls = this->findCollisions(dmat);
std::map<int, unsigned int> doneBonds;
std::map<int, unsigned int> doneSpiros;
unsigned int iter = 0;
while (iter < MAX_COLL_ITERS && colls.size()) {
auto ncols = colls.size();
if (ncols > 0) {
// we have a collision
auto cAids = colls[0];
auto rotBonds = getRotatableBonds(*dp_mol, cAids.first, cAids.second);
auto prevDensity = this->totalDensity();
for (auto ri : rotBonds) {
auto doneBondsRiIt = doneBonds.find(ri);
if ((doneBondsRiIt == doneBonds.end()) ||
(doneBondsRiIt->second < NUM_BONDS_FLIPS)) {
if (doneBondsRiIt == doneBonds.end()) {
doneBonds[ri] = 1;
} else {
doneBondsRiIt->second += 1;
}
bool resolved = false;
flipAboutBond(ri);
colls = this->findCollisions(dmat);
auto newDensity = this->totalDensity();
if (colls.size() < ncols) {
doneBonds[ri] = NUM_BONDS_FLIPS; // lock this rotatable bond
break;
} else if (colls.size() == ncols && newDensity < prevDensity) {
break;
} else {
// we made the wrong move earlier - reject the flip move it back
flipAboutBond(ri);
colls = this->findCollisions(dmat);
// and try the other end:
flipAboutBond(ri, false);
colls = this->findCollisions(dmat);
newDensity = this->totalDensity();
if (colls.size() < ncols) {
doneBonds[ri] = NUM_BONDS_FLIPS; // lock this rotatable bond
break;
} else if (colls.size() == ncols && newDensity < prevDensity) {
break;
} else {
flipAboutBond(ri, false);
colls = this->findCollisions(dmat);
}
}
}
// Try bond flipping first
resolved = tryResolvingCollisionWithBondFlip(cAids, ncols, prevDensity,
doneBonds, dmat);
// Try spiro flipping if bond flipping didn't resolve the collision
if (!resolved) {
resolved = tryResolvingCollisionWithSpiroFlip(
cAids, ncols, prevDensity, doneSpiros, spiroCenters, dmat);
}
// Re-check collisions after flipping
colls = this->findCollisions(dmat);
}
++iter;
}

29
Code/GraphMol/Depictor/EmbeddedFrag.h
View File

@@ -16,6 +16,7 @@
#include <Geometry/point.h>
#include "DepictUtils.h"
#include <boost/smart_ptr.hpp>
#include <boost/dynamic_bitset.hpp>
namespace RDKit {
class ROMol;
@@ -322,6 +323,12 @@ class RDKIT_DEPICTOR_EXPORT EmbeddedFrag {
*/
void flipAboutBond(unsigned int bondId, bool flipEnd = true);
//! \brief flip one ring of a spiro compound to resolve collisions
/*!
\param spiroAid - the spiro center atom index
*/
void flipAboutSpiroCenter(unsigned int spiroAid);
void openAngles(const double *dmat, unsigned int aid1, unsigned int aid2);
std::vector<PAIR_I_I> findCollisions(const double *dmat,
@@ -341,9 +348,11 @@ class RDKIT_DEPICTOR_EXPORT EmbeddedFrag {
double mimicDmatWt = 0.0,
bool permuteDeg4Nodes = false);
//! Remove collisions in a structure by flipping rotatable bonds
//! Remove collisions in a structure by flipping rotatable bonds and spiro centers
//! along the shortest path between two colliding atoms
void removeCollisionsBondFlip();
void removeCollisionsBondAndSpiroFlip();
[[deprecated("please use removeCollisionsBondAndSpiroFlip()")]] void removeCollisionsBondFlip() { removeCollisionsBondAndSpiroFlip(); };
//! Remove collision by opening angles at the offending atoms
void removeCollisionsOpenAngles();
@@ -375,6 +384,22 @@ class RDKIT_DEPICTOR_EXPORT EmbeddedFrag {
private:
double totalDensity();
// Helper methods for collision resolution
bool tryResolvingCollisionWithBondFlip(
const std::pair<unsigned int, unsigned int> &cAids,
unsigned int ncols,
double prevDensity,
std::map<int, unsigned int> &doneBonds,
const double *dmat);
bool tryResolvingCollisionWithSpiroFlip(
const std::pair<unsigned int, unsigned int> &cAids,
unsigned int ncols,
double prevDensity,
std::map<int, unsigned int> &doneSpiros,
const boost::dynamic_bitset<> &spiroCenters,
const double *dmat);
// returns true if fused rings found a template
bool matchToTemplate(const RDKit::INT_VECT &ringSystemAtoms);

2
Code/GraphMol/Depictor/RDDepictor.cpp
View File

@@ -611,7 +611,7 @@ unsigned int compute2DCoords(RDKit::ROMol &mol,
params.nFlipsPerSample, params.nSamples, params.sampleSeed, nullptr,
0.0, params.permuteDeg4Nodes);
} else {
eri.removeCollisionsBondFlip();
eri.removeCollisionsBondAndSpiroFlip();
}
}
for (auto &eri : efrags) {

159
Code/GraphMol/Depictor/catch_tests.cpp
View File

@@ -945,7 +945,8 @@ M END
MolTransforms::getAngleDeg(wedgedMolCopy.getConformer(), 23, 26, 25);
CHECK((angle > 145. && angle < 150.));
for (const auto &p : wedgePairs) {
CHECK(getBondDirBetween(wedgedMolCopy, p.first, p.second) == Bond::NONE);
CHECK(getBondDirBetween(wedgedMolCopy, p.first, p.second) ==
Bond::NONE);
}
}
// the "rebuildCoordGen" alignment should succeed and keep original wedging
@@ -1052,7 +1053,8 @@ M END
MolTransforms::getAngleDeg(wedgedMolCopy.getConformer(), 23, 26, 25);
CHECK((angle > 105. && angle < 110.));
for (const auto &p : wedgePairs) {
CHECK(getBondDirBetween(wedgedMolCopy, p.first, p.second) == Bond::NONE);
CHECK(getBondDirBetween(wedgedMolCopy, p.first, p.second) ==
Bond::NONE);
}
}
// the "rebuild" alignment should succeed and preserve molblock wedging
@@ -1091,7 +1093,8 @@ M END
MolTransforms::getAngleDeg(wedgedMolCopy.getConformer(), 23, 26, 25);
CHECK((angle > 145. && angle < 150.));
for (const auto &p : wedgePairs) {
CHECK(getBondDirBetween(wedgedMolCopy, p.first, p.second) == Bond::NONE);
CHECK(getBondDirBetween(wedgedMolCopy, p.first, p.second) ==
Bond::NONE);
}
}
// the "rebuildCoordGen" alignment should succeed and keep original wedging
@@ -2497,9 +2500,8 @@ TEST_CASE("macrocycle templating") {
params.useRingTemplates = false;
RDDepict::compute2DCoords(*mol, params);
auto withoutTemplates =
mol->getConformer().getAtomPos(0) -
mol->getConformer().getAtomPos(ringSize / 2);
auto withoutTemplates = mol->getConformer().getAtomPos(0) -
mol->getConformer().getAtomPos(ringSize / 2);
// Generate coordinates WITH templates
params.useRingTemplates = true;
@@ -2523,4 +2525,149 @@ TEST_CASE("macrocycle templating") {
CHECK(templatesUsed == expectedTemplatesUsed);
}
}
}
TEST_CASE("spiro center detection") {
SECTION("true spiro compounds") {
auto [smiles, spiroAtom] = GENERATE(table<std::string, unsigned int>({
{"C1CCC2(C1)CCCCC2", 3}, // spiro[4.5]decane, atom 3
{"C1CCCC2(C1)CCCCC2", 4} // spiro[5.5]undecane, atom 4
}));
CAPTURE(smiles, spiroAtom);
std::unique_ptr<RWMol> m(SmilesToMol(smiles));
REQUIRE(m);
MolOps::findSSSR(*m);
// Check that the expected atom is a spiro center
CHECK(RDDepict::isSpiroCenter(spiroAtom, m.get()));
// Other atoms should not be spiro centers
for (unsigned int i = 0; i < m->getNumAtoms(); ++i) {
if (i != spiroAtom) {
CHECK_FALSE(RDDepict::isSpiroCenter(i, m.get()));
}
}
}
SECTION("non-spiro compounds - no atoms should be spiro centers") {
auto smiles = GENERATE("C1CCC2CCCCC2C1", // fused rings (decalin)
"C1CC2CCC1CC2", // bridged ring (norbornane)
"C1CCCCC1" // simple ring (cyclohexane)
);
CAPTURE(smiles);
std::unique_ptr<RWMol> m(SmilesToMol(smiles));
REQUIRE(m);
MolOps::findSSSR(*m);
for (unsigned int i = 0; i < m->getNumAtoms(); ++i) {
CHECK_FALSE(RDDepict::isSpiroCenter(i, m.get()));
}
}
SECTION("spiro with substituents - should find at least one spiro center") {
auto m = "CC1CCC2(C1)CCCCC2(C)C"_smiles;
REQUIRE(m);
MolOps::findSSSR(*m);
bool foundSpiro = false;
for (unsigned int i = 0; i < m->getNumAtoms(); ++i) {
if (RDDepict::isSpiroCenter(i, m.get())) {
foundSpiro = true;
break;
}
}
CHECK(foundSpiro);
}
SECTION("dispiro compound - should find exactly two spiro centers") {
auto m = "C1CCC2(C1)CCC1(CC2)CCCC1"_smiles;
REQUIRE(m);
MolOps::findSSSR(*m);
int spiroCount = 0;
for (unsigned int i = 0; i < m->getNumAtoms(); ++i) {
if (RDDepict::isSpiroCenter(i, m.get())) {
++spiroCount;
}
}
CHECK(spiroCount == 2);
}
}
TEST_CASE("spiro flipping for collision resolution") {
auto smiles = GENERATE(
"C1CCC2(C1)CCCCC2", // spiro[4.5]decane
"C1CCCC2(C1)CCCCC2", // spiro[5.5]undecane
"CC1CCC2(C1)CCCC(C)C2", // spiro with substituents
"CC1CCC2(C1)CCCCC2(C)C", // complex spiro with multiple substituents
"C1CCC2(C1)CCC1(CC2)CCCC1" // dispiro compound
);
CAPTURE(smiles);
std::unique_ptr<RWMol> m(SmilesToMol(smiles));
REQUIRE(m);
CHECK(RDDepict::compute2DCoords(*m) == 0);
// Verify no severe collisions (all non-bonded atoms should be reasonably
// separated)
auto &conf = m->getConformer();
for (unsigned int i = 0; i < m->getNumAtoms(); ++i) {
for (unsigned int j = i + 1; j < m->getNumAtoms(); ++j) {
// Skip bonded atoms
if (m->getBondBetweenAtoms(i, j)) {
continue;
}
auto pos = conf.getAtomPos(i) - conf.getAtomPos(j);
auto dist = pos.length();
CHECK(dist > 0.35); // Minimum reasonable separation
}
}
}
TEST_CASE("complex spiro structure from MOL file - reasonable bond lengths") {
std::string rdbase = getenv("RDBASE");
std::string molfile =
rdbase + "/Code/GraphMol/Depictor/test_data/spiro_complex.mol";
std::unique_ptr<RWMol> m(MolFileToMol(molfile));
REQUIRE(m);
// Generate new 2D coordinates
CHECK(RDDepict::compute2DCoords(*m) == 0);
auto &conf = m->getConformer();
// Check that all bond lengths are reasonable (within ±30% of standard bond
// length)
const double expectedBondLength = RDDepict::BOND_LEN;
const double tolerance = 0.30; // ±30%
const double minBondLength = expectedBondLength * (1.0 - tolerance);
const double maxBondLength = expectedBondLength * (1.0 + tolerance);
for (const auto &bond : m->bonds()) {
unsigned int i = bond->getBeginAtomIdx();
unsigned int j = bond->getEndAtomIdx();
auto pos = conf.getAtomPos(i) - conf.getAtomPos(j);
auto bondLength = pos.length();
// Bond lengths should be within ±30% of RDDepict::BOND_LEN (typically 1.5)
CHECK(bondLength >= minBondLength);
CHECK(bondLength <= maxBondLength);
INFO("Bond " << i << "-" << j << " length: " << bondLength << " (expected: "
<< expectedBondLength << " ±" << (tolerance * 100) << "%)");
}
// Also verify no severe atomic collisions
for (unsigned int i = 0; i < m->getNumAtoms(); ++i) {
for (unsigned int j = i + 1; j < m->getNumAtoms(); ++j) {
if (m->getBondBetweenAtoms(i, j)) {
continue;
}
auto pos = conf.getAtomPos(i) - conf.getAtomPos(j);
auto dist = pos.length();
CHECK(dist > 0.35);
}
}
}

2
Code/GraphMol/Depictor/testDepictor.cpp
View File

@@ -385,7 +385,7 @@ void testIssue248() {
++token) {
std::string smi = *token;
RWMol *m = SmilesToMol(smi, 0, 1);
unsigned int confId = RDDepict::compute2DCoords(*m);
unsigned int confId = RDDepict::compute2DCoords(*m, nullptr, false, true, 3, 100);
// check that there are no collisions in the molecules
int natms = m->getNumAtoms();
int i, j;

70
Code/GraphMol/Depictor/test_data/spiro_complex.mol Normal file
View File

@@ -0,0 +1,70 @@
spiro_complex
RDKit 2D
0 0 0 0 0 999 V3000
M V30 BEGIN CTAB
M V30 COUNTS 27 30 0 0 0
M V30 BEGIN ATOM
M V30 1 C -0.000000 10.404690 0.000000 0
M V30 2 C 0.750000 9.105652 0.000000 0
M V30 3 C 2.250000 9.105652 0.000000 0
M V30 4 C 3.000000 10.404690 0.000000 0
M V30 5 C 2.250000 11.703729 0.000000 0
M V30 6 C 0.750000 11.703729 0.000000 0
M V30 7 C 1.500000 7.806614 0.000000 0
M V30 8 C 0.750000 6.507576 0.000000 0
M V30 9 C -0.750000 6.507576 0.000000 0
M V30 10 C -1.500000 7.806614 0.000000 0
M V30 11 C -0.750000 9.105652 0.000000 0
M V30 12 C 0.914538 11.175722 0.000000 0
M V30 13 C 0.194639 11.158341 0.000000 0
M V30 14 C 0.539536 10.526200 0.000000 0
M V30 15 C -2.967221 8.118482 0.000000 0
M V30 16 C -3.124014 9.610265 0.000000 0
M V30 17 C -1.753696 10.220370 0.000000 0
M V30 18 C -2.923052 12.958341 0.000000 0
M V30 19 C -2.581939 9.712862 0.000000 0
M V30 20 N -3.696656 8.709166 0.000000 0
M V30 21 N 4.500000 10.404690 0.000000 0
M V30 22 N 3.000000 7.806614 0.000000 0
M V30 23 C -4.081939 7.114786 0.000000 0
M V30 24 C -5.508523 7.578311 0.000000 0
M V30 25 C -5.972049 6.151727 0.000000 0
M V30 26 C -5.044998 9.004896 0.000000 0
M V30 27 C -6.935108 8.041837 0.000000 0
M V30 END ATOM
M V30 BEGIN BOND
M V30 1 1 1 2
M V30 2 1 2 3
M V30 3 1 3 4
M V30 4 1 4 5
M V30 5 1 5 6
M V30 6 1 6 1
M V30 7 1 7 8
M V30 8 1 8 9
M V30 9 1 9 10
M V30 10 1 10 11
M V30 11 1 7 2
M V30 12 1 2 11
M V30 13 1 12 13
M V30 14 2 13 14
M V30 15 1 1 14
M V30 16 2 12 6
M V30 17 1 15 16
M V30 18 2 16 17
M V30 19 1 11 17
M V30 20 2 15 10
M V30 21 1 13 18
M V30 22 1 14 19
M V30 23 3 19 20
M V30 24 1 4 21
M V30 25 1 3 22
M V30 26 1 15 23
M V30 27 1 23 24
M V30 28 1 24 25
M V30 29 1 24 26
M V30 30 1 24 27
M V30 END BOND
M V30 END CTAB
M END
$$