molecular-standardization

Name: molecular-standardization
Author: GPTomics

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How to install molecular-standardization?

gptomics/bioskills/molecular-standardization

$npx -y skills add GPTomics/bioSkills --skill molecular-standardization

Installs into the current project.

Summary

Standardizes molecular structures using the ChEMBL structure pipeline for normalization and parent selection plus RDKit rdMolStandardize for explicit custom steps such as tautomer canonicalization, salt/solvent stripping, charge handling, stereochemistry handling, mixture selecti

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SKILL.md

1	## Version Compatibility
2
3	Reference examples tested with: RDKit 2024.09+ and chembl_structure_pipeline 1.2+. MolVS 0.1.1 is a legacy package; use RDKit's maintained `rdMolStandardize` module for custom pipelines.
4
5	Before using code patterns, verify installed versions match. If versions differ:
6	- Python: `pip show <package>` then `help(module.function)` to check signatures
7
8	If code throws ImportError, AttributeError, or TypeError, introspect the installed
9	package and adapt the example to match the actual API rather than retrying.
10
11	# Molecular Standardization
12
13	Convert raw molecular structures into a consistent form for ML training data, deduplication, registry, and cross-database joining. Skipping standardization can create data leakage when alternate representations of one compound enter different splits, distort QSAR inputs, and cause database join misses. The ChEMBL structure pipeline (Bento et al. 2020) is built on RDKit and applies ChEMBL-specific normalization and parent-selection rules. canSARchem (Dolciami et al. 2022) adds canonical-tautomer selection before parent extraction. RDKit's maintained `rdMolStandardize` module provides primitives for building an explicit custom pipeline.
14
15	For format-level I/O and aromaticity perception, see `chemoinformatics/molecular-io`. For descriptor calculation after standardization, see `chemoinformatics/molecular-descriptors`.
16
17	## Standardization Pipeline Stages
18
19	\| Stage \| RDKit Tool \| Operation \| Common errors caught \|
20	\|-------\|-----------\|-----------\|----------------------\|
21	\| 1. Sanitization \| `Chem.SanitizeMol` \| Kekulize, assign aromaticity, fix valences \| Wrong valence on N/O \|
22	\| 2. Salt stripping \| `rdMolStandardize.FragmentRemover` or `LargestFragmentChooser` \| Remove counterions \| Cl-, Na+, K+, OH- \|
23	\| 3. Mixture choice \| `LargestFragmentChooser` \| Pick parent fragment \| Co-crystals, hydrates \|
24	\| 4. Charge neutralization \| `Uncharger` \| Neutralize while preserving net charge \| Permanent charges preserved (quaternary N+) \|
25	\| 5. Tautomer canonicalization \| `TautomerEnumerator.Canonicalize` \| Pick canonical tautomer \| Keto/enol; amide/imidate \|
26	\| 6. Stereo standardization \| `Chem.AssignStereochemistry` \| Consistent stereo descriptors \| Lost wedges, ambiguous R/S \|
27	\| 7. Isotope normalization \| Explicitly set selected atom isotope labels to 0 \| Remove 13C, 2H labels \| Tracer studies; preserve labels when scientifically meaningful \|
28	\| 8. Output canonicalization \| `Chem.MolToSmiles(canonical=True)` \| Canonical SMILES + InChIKey \| Round-trip stability \|
29
30	## Pipeline Reconciliation
31
32	\| Pipeline \| Origin \| Tautomer canonicalization \| Salt definition \| Use case \|
33	\|----------\|--------\|---------------------------\|-----------------\|----------\|
34	\| ChEMBL pipeline \| EBI ChEMBL \| Not performed by `standardize_mol` or `get_parent_mol` \| ChEMBL salt list (extensive) \| ChEMBL-compatible registration \|
35	\| canSARchem \| ICR Cancer Research UK \| Canonical tautomer BEFORE parent extraction \| Extended salt list \| Cancer drug discovery \|
36	\| PubChem (OpenEye) \| NIH NCBI \| OpenEye QUACPAC tautomer \| PubChem salt list \| Bioassay data, large-scale \|
37	\| RDKit rdMolStandardize default \| Greg Landrum \| RDKit TautomerEnumerator \| RDKit default \| General purpose, open source \|
38
39	Key difference (canSARchem vs ChEMBL):
40	- ChEMBL standardizes the representation and extracts a parent, but does not canonicalize tautomers.
41	- canSARchem canonicalizes the tautomer before parent extraction.
42
43	This difference matters when alternate tautomeric inputs must be registered as one parent. Do not describe ChEMBL output as tautomer-canonical unless an explicit tautomer step is added and documented.
44
45	## ChEMBL Structure Pipeline (Reference Implementation)
46
47	ChEMBL's standardization is the most widely-used reference. The Python package `chembl_structure_pipeline` exposes the validated pipeline.
48
49	Goal: Apply the industry-reference ChEMBL standardization pipeline to a SMILES.
50
51	Approach: Parse SMILES with RDKit, run `standardize_mol` (sanitize, normalize, and standardize charges), then `get_parent_mol` (strip salts/counter-ions), and emit canonical SMILES. Add `rdMolStandardize.TautomerEnumerator` separately only when the project requires tautomer canonicalization.
52
53	```python
54	from chembl_structure_pipeline import standardize_mol, get_parent_mol
55	from rdkit import Chem
56
57	def ch

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molecular-standardization

1.1kstars185forks

View on GitHub

How to install molecular-standardization?

gptomics/bioskills/molecular-standardization

$npx -y skills add GPTomics/bioSkills --skill molecular-standardization

Installs into the current project.

Summary

Files · 1

View on GitHub

SKILL.md

1	## Version Compatibility
2
3	Reference examples tested with: RDKit 2024.09+ and chembl_structure_pipeline 1.2+. MolVS 0.1.1 is a legacy package; use RDKit's maintained `rdMolStandardize` module for custom pipelines.
4
5	Before using code patterns, verify installed versions match. If versions differ:
6	- Python: `pip show <package>` then `help(module.function)` to check signatures
7
8	If code throws ImportError, AttributeError, or TypeError, introspect the installed
9	package and adapt the example to match the actual API rather than retrying.
10
11	# Molecular Standardization
12
13	Convert raw molecular structures into a consistent form for ML training data, deduplication, registry, and cross-database joining. Skipping standardization can create data leakage when alternate representations of one compound enter different splits, distort QSAR inputs, and cause database join misses. The ChEMBL structure pipeline (Bento et al. 2020) is built on RDKit and applies ChEMBL-specific normalization and parent-selection rules. canSARchem (Dolciami et al. 2022) adds canonical-tautomer selection before parent extraction. RDKit's maintained `rdMolStandardize` module provides primitives for building an explicit custom pipeline.
14
15	For format-level I/O and aromaticity perception, see `chemoinformatics/molecular-io`. For descriptor calculation after standardization, see `chemoinformatics/molecular-descriptors`.
16
17	## Standardization Pipeline Stages
18
19	\| Stage \| RDKit Tool \| Operation \| Common errors caught \|
20	\|-------\|-----------\|-----------\|----------------------\|
21	\| 1. Sanitization \| `Chem.SanitizeMol` \| Kekulize, assign aromaticity, fix valences \| Wrong valence on N/O \|
22	\| 2. Salt stripping \| `rdMolStandardize.FragmentRemover` or `LargestFragmentChooser` \| Remove counterions \| Cl-, Na+, K+, OH- \|
23	\| 3. Mixture choice \| `LargestFragmentChooser` \| Pick parent fragment \| Co-crystals, hydrates \|
24	\| 4. Charge neutralization \| `Uncharger` \| Neutralize while preserving net charge \| Permanent charges preserved (quaternary N+) \|
25	\| 5. Tautomer canonicalization \| `TautomerEnumerator.Canonicalize` \| Pick canonical tautomer \| Keto/enol; amide/imidate \|
26	\| 6. Stereo standardization \| `Chem.AssignStereochemistry` \| Consistent stereo descriptors \| Lost wedges, ambiguous R/S \|
27	\| 7. Isotope normalization \| Explicitly set selected atom isotope labels to 0 \| Remove 13C, 2H labels \| Tracer studies; preserve labels when scientifically meaningful \|
28	\| 8. Output canonicalization \| `Chem.MolToSmiles(canonical=True)` \| Canonical SMILES + InChIKey \| Round-trip stability \|
29
30	## Pipeline Reconciliation
31
32	\| Pipeline \| Origin \| Tautomer canonicalization \| Salt definition \| Use case \|
33	\|----------\|--------\|---------------------------\|-----------------\|----------\|
34	\| ChEMBL pipeline \| EBI ChEMBL \| Not performed by `standardize_mol` or `get_parent_mol` \| ChEMBL salt list (extensive) \| ChEMBL-compatible registration \|
35	\| canSARchem \| ICR Cancer Research UK \| Canonical tautomer BEFORE parent extraction \| Extended salt list \| Cancer drug discovery \|
36	\| PubChem (OpenEye) \| NIH NCBI \| OpenEye QUACPAC tautomer \| PubChem salt list \| Bioassay data, large-scale \|
37	\| RDKit rdMolStandardize default \| Greg Landrum \| RDKit TautomerEnumerator \| RDKit default \| General purpose, open source \|
38
39	Key difference (canSARchem vs ChEMBL):
40	- ChEMBL standardizes the representation and extracts a parent, but does not canonicalize tautomers.
41	- canSARchem canonicalizes the tautomer before parent extraction.
42
43	This difference matters when alternate tautomeric inputs must be registered as one parent. Do not describe ChEMBL output as tautomer-canonical unless an explicit tautomer step is added and documented.
44
45	## ChEMBL Structure Pipeline (Reference Implementation)
46
47	ChEMBL's standardization is the most widely-used reference. The Python package `chembl_structure_pipeline` exposes the validated pipeline.
48
49	Goal: Apply the industry-reference ChEMBL standardization pipeline to a SMILES.
50
51	Approach: Parse SMILES with RDKit, run `standardize_mol` (sanitize, normalize, and standardize charges), then `get_parent_mol` (strip salts/counter-ions), and emit canonical SMILES. Add `rdMolStandardize.TautomerEnumerator` separately only when the project requires tautomer canonicalization.
52
53	```python
54	from chembl_structure_pipeline import standardize_mol, get_parent_mol
55	from rdkit import Chem
56
57	def ch

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