xchem-fragmenstein 1.0.0

Merging, linking and placing compounds by stitching them together like a reanimated corpse

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. For GitHub documentation see:

• Installation
• Theory
• Python usage — ideal for coders!
• Examples
• Command line usage — ideal for non-coders!
• Limitations
• Manuscript data repository
• Paper Authors
• FAQ

Badges and notebooks

Example of multiple applications:

Name	Colab Link	PyRosetta	Description
Light		❌	Generate molecules and see how they merge and how a placed compound fairs
Pipeline w/o Pyrosetta		❌	Given a template and a some hits, merge them and place the most similar purchasable analogues from Enamine REAL
Pipeline w/ PyRosetta		✔	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
• Figures for the upcoming manuscript are in a separate repo
• The conversion of a rdkit Chem.Mol that cannot be sanitised to an analogue that can is done by the molecular rectifier package
• The conversion of a rdkit Chem.Mol to a PyRosetta residue type (a "params file") is done via the rdkit-to-params package
• The pipeline demo colab notebook uses Brian Shoichet's SmallWorld webapp, interfaced via its API in Python
• The playground demo colab notebook features a JSME widget — JSME is a popular JS only molecular editor
• 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)
• Fragmenstein combine route does not check if a compound is purchasable. Above NextMove Software SmallWorld is used (SmallWorld hosted by John Irwin) to find the top N analogues, via an API.
• In 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) and then placed with Fragmenstein.
• Steph Wills's fragment network merges repo enumerates superstructures of two parent hits from catalogue and places them with Fragmenstein.
• SynDirElla performs a retrosynthesis of a compound, enumerates close analogues of the synthons and places their combinations