Yakov Pechersky c6cabf4153 Speed-up tautomer canonicalization, no API changes (#9134) ...

* Speed up tautomer canonicalization by deferring on SSSR calc

* Lazy kekulization for tautomer enumeration

Defer kekulization of tautomers until they are actually needed for
transform matching. This avoids creating kekulized copies for:
1. The initial tautomer (until first iteration)
2. New tautomers that may never be processed (if enumeration ends early)

The Tautomer class now supports lazy initialization of the kekulized
form via getKekulized() method.

Performance improvement: ~7% additional speedup (total ~22-24% from baseline)

* Use count-only substructure matching in tautomer scoring

* Add SubstructMatchCount regression test

* MolStandardize: reduce enumerate overhead

* MolStandardize: avoid per-tautomer ring recomputation

* Atom: cache PeriodicTable pointer in valence calcs

* Atom: reuse PeriodicTable in getEffectiveAtomicNum

* PeriodicTable: add atomic fast path for getTable

* GraphMol: reduce ROMol copy reallocations

* MolStandardize: use quickCopy for per-match product copies

Use RWMol(*kmol, true) in tautomer enumeration to avoid copying properties/bookmarks/conformers for each candidate. This reduces deep-copy overhead without changing chemistry.

* MolStandardize: pre-filter scoring patterns by element/connectivity

For tautomer scoring, pre-compute which SubstructTerms are relevant for
a given input molecule. Since tautomerization only moves H atoms and
changes bond orders (never creates/destroys heavy-atom bonds), patterns
requiring missing elements or connectivity can be skipped for all
tautomers of that molecule.

Two-stage filtering:
1. Element check: skip patterns requiring atoms not in the molecule
2. Connectivity check: skip patterns whose bond-order-agnostic structure
   doesn't match the input molecule's connectivity

This reduces the number of VF2 substructure calls per tautomer from 12
to typically 3-5, depending on the molecule's composition.

* MolStandardize: preserve molecule properties for canonical tautomer

Copy molecule properties from the original input to the canonical tautomer
result. Since quickCopy during enumeration skips d_props to avoid overhead,
extended SMILES data like link nodes (LN) was lost. This restores them
on the final result.

* TautomerQuery: preserve molecule properties (e.g. link nodes) in tautomers

TautomerQuery::fromMol() uses TautomerEnumerator::enumerate() which uses
quickCopy for performance. This doesn't copy molecule properties like
_molLinkNodes. Without this fix, XQMol output would lose link node
extensions in the SMILES.

Copy properties from the original query molecule to all enumerated
tautomers before constructing the TautomerQuery. This preserves extended
SMILES data without impacting enumeration performance.

* MolStandardize: use parallel iteration and cache bond lookups

Replace O(n) getAtomWithIdx/getBondWithIdx calls with parallel iteration
over atom/bond ranges in canonicalizeInPlace and enumerate. Cache bond
lookups in setTautomerStereoAndIsoHs to avoid repeated O(n) searches.

* perf: add specialized matchers for simple tautomer scoring patterns

Replace VF2 graph matching with O(n) loops for 6 simple patterns:
- countDoubleOrAromaticBonds: C=O, N=O, P=O patterns
- countMethyls: [CX4H3] methyl groups
- countCarbonDoubleHetero: [C]=[/home/dcvuser/rdkit;Code/GraphMol/MolStandardize/Tautomer.h] aliphatic C=hetero
- countAromaticCarbonExocyclicN: [c]=aromatic C=exocyclic N
Complex patterns (benzoquinone, oxim, guanidine, aci-nitro) still use VF2.
Combined with the pre-filtering optimization, this achieves ~3.7x speedup
(~2500ms vs ~9300ms original) for tautomer canonicalization.

* Fix tautomer canonicalize dropping conformers from quickCopy

quickCopy (RWMol(*mol, true)) skips conformers, so tautomer
enumeration products lose 2D/3D coordinates. This causes InChI
generation to omit the /b (double bond E/Z stereo) layer, since
E/Z is derived from atomic coordinates.

Fix: copy conformers from the original molecule onto the canonical
tautomer after pickCanonical in TautomerEnumerator::canonicalize().

Tests: SMILES-based E/Z check in testTautomer.cpp, molblock-based
conformer preservation check in catch_tests.cpp.

* add test on canonicalize losing stereo

* add regression test for exocyclic C=C tautomer canonicalization

The getTautomerStateKey() pre-filter (commit 2595ef748) can falsely
deduplicate distinct tautomers when their atom-index-ordered state
patterns happen to match, leading canonicalize() to pick the wrong
canonical form for molecules with STEREOTRANS-pinned exocyclic C=C
bonds after RemoveHs.

Test verifies that O=C(CC1=CC2=CC=COC2)NC1=O canonicalizes to the
exocyclic form O=C1CC(=CC2=CC=COC2)C(=O)N1, not the endocyclic form
O=C1C=C(C=C2CC=COC2)C(=O)N1.

Currently expected to FAIL until the state key dedup bug is fixed.

* MolStandardize: expand tautomer connectivity SMARTS

* MolStandardize: scope tautomer pattern enum

* MolStandardize: trim tautomer pattern enum

* MolStandardize: use symmetric ring scoring

2026-03-31 06:42:40 +02:00

31 KiB

Raw Blame History

View Raw