from fragmenstein.laboratory.validator import hits_check
# Fragmenstein
## Stitched molecules
Fragmenstein: Merging, linking and placing compounds by stitching bound compounds together like a reanimated corpse.
Fragmenstein can perform two different tasks:
* **Combine** hits (merging and linking) based on their atomic overlap
* **Place** a given followup molecule based on one or more parent hits
NB. Whereas docking uses pre-generates comformers and finds the best pose that best matches the parent (if set-up to do so),
Fragmenstein creates a monstrous comformer from the parent(s) and then minimises it, optionally in the protein.
Hence why I call it a 'placement' not docking tool.
## Index
For documentation in Read-the-documents see [fragmenstein.readthedocs.io](https://fragmenstein.readthedocs.io/en/latest/).
For GitHub documentation see:
* [Installation](doc_00_installation.html)
* [Theory](doc_01_workings.html)
* [Python usage](doc_02_usage.html) — ideal for coders!
* [Examples](doc_03_examples.html)
* [Command line usage](doc_04_cmd.html) — ideal for non-coders!
* [Limitations](doc_05_limitations.html)
* [Manuscript data repository](https://github.com/matteoferla/Fragmenstein-manuscript-data.html)
* [Paper Authors](doc_06_authors.html)
* [FAQ](doc_07_FAQ.html)
## Badges and notebooks
[](https://fragmenstein.readthedocs.io/en/latest/?badge=latest)
[](https://github.com/matteoferla/Fragmenstein)
[](https://github.com/matteoferla/Fragmenstein)
[](https://github.com/matteoferla/Fragmenstein)
[](https://github.com/matteoferla/Fragmenstein)
[](https://github.com/matteoferla/Fragmenstein/raw/master/LICENCE)
[](https://github.com/matteoferla/Fragmenstein)
[](https://github.com/matteoferla/Fragmenstein)
[](https://github.com/matteoferla/Fragmenstein)
[](https://github.com/matteoferla/Fragmenstein)
[](https://pypi.org/project/fragmenstein)
[](https://pypi.org/project/fragmenstein)
[](https://pypi.org/project/fragmenstein)
[](https://pypi.org/project/fragmenstein)
[](https://pypi.org/project/fragmenstein)
[](https://pypi.org/project/fragmenstein)
[](https://codeclimate.com/github/matteoferla/Fragmenstein)
[](https://codeclimate.com/github/matteoferla/Fragmenstein)
[](https://codeclimate.com/github/matteoferla/Fragmenstein)
Example of multiple applications: [](https://www.youtube.com/watch?v=kieDWYkzmiE)
| Name | Colab Link | PyRosetta | Description |
|:-----------------------|:---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| :---: | :--- |
| Light | [](https://colab.research.google.com/github/matteoferla/Fragmenstein/blob/master/colab-notebooks/colab_playground.ipynb) | ❌| Generate molecules and see how they merge
and how a placed compound fairs|
| Pipeline w/o Pyrosetta | [](https://colab.research.google.com/github/matteoferla/Fragmenstein/blob/master/colab-notebooks/colab_fragmenstein_Wictor.ipynb) | ❌| Given a template and a some hits,
merge them
and place the most similar purchasable analogues from Enamine REAL |
| Pipeline w/ PyRosetta | [](https://colab.research.google.com/github/matteoferla/Fragmenstein/blob/master/colab-notebooks/colab_fragmenstein.ipynb) | ✔| Given a template and a some hits,
merge them
and place the most similar purchasable analogues from Enamine REAL |
## See Also
* ChemRXiv preprint — https://chemrxiv.org/engage/chemrxiv/article-details/65d751ab9138d23161b7ea38
* Fragmenstein is used in Schuller et. al. 2021
[](https://doi.org/10.1126%2Fsciadv.abf8711)
* Figures for the upcoming manuscript are in a separate
[repo](https://github.com/matteoferla/Fragmenstein-manuscript-data)
* The conversion of a rdkit Chem.Mol that cannot be sanitised to an analogue that can
is done by the [molecular rectifier package](https://github.com/matteoferla/molecular_rectifier)
* The conversion of a rdkit Chem.Mol to a PyRosetta residue type (a "params file") is done via
the [rdkit-to-params package](https://github.com/matteoferla/rdkit_to_params)
* The pipeline demo colab notebook uses Brian Shoichet's [SmallWorld webapp](https://sw.docking.org/),
interfaced via [its API in Python](https://github.com/matteoferla/Python_SmallWorld_API)
* The playground demo colab notebook features a [JSME widget](https://github.com/matteoferla/JSME_notebook_hack) —
[JSME](http://www.jcheminf.com/content/5/1/24) is a popular JS only molecular editor
* [Molecular Rectifier](https://github.com/matteoferla/molecular_rectifier) is used to correct the mistakes in the merged molecules,
and is usable for other algorithms, especially de novo design via denoising diffusion probabilistic models
(cf [blogpost discussion for the latter](https://www.blopig.com/blog/2024/09/out-of-the-box-rdkit-valid-is-an-imperfect-metric-a-review-of-the-kekulizeexception-and-nitrogen-protonation-to-correct-this/))
* Fragmenstein combine route does not check if a compound is purchasable. Above NextMove Software SmallWorld is used
([SmallWorld hosted by John Irwin](sw.docking.org)) to find the top N analogues,
via [an API](https://github.com/matteoferla/Python_SmallWorld_API).
* In [Arthorian Quest](https://github.com/matteoferla/Arthorian-Quest), a parent combound is coverted with ease into an ambiguous SMARTS pattern,
catalogue compounds are searched with NextMove Software's Arthor ([hosted by John Irwin](arthor.docking.org)) and then placed with Fragmenstein.
* Steph Wills's [fragment network merges repo](https://github.com/stephwills/fragment_network_merges)
enumerates superstructures of two parent hits from catalogue and places them with Fragmenstein.
* [SynDirElla](https://github.com/kate-fie/syndirella) performs a retrosynthesis of a compound, enumerates close analogues of the synthons and places their combinations