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Merge pull request #68 from volkamerlab/update_READMEs
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Update README's
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kabu00002 authored May 6, 2024
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12 changes: 6 additions & 6 deletions README.md
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3.1. Notebooks covering the full analyses regarding the fragment and combinatorial libraries as described in
the corresponding paper.
3.2. WIP: Notebooks providing a custom filtering framework to reduce the fragment library size.
3.2. Notebooks providing a custom filtering framework to reduce the fragment library size.

Please find detailed description of files in `data/` and `notebooks/` in the folders' `README` files.
Please find detailed descriptions of files in `data/` and `notebooks/` in the folders' `README` files.

## Description

**Exploring the kinase inhibitor space using subpocket-focused fragmentation and recombination**

Protein kinases play a crucial role in many cell signaling processes,
making them one of the most important families of drug targets.
Fragment-based drug design has proven useful as one approach to develop novel kinase inhibitors.
Fragment-based drug design has proven useful as one approach to developing novel kinase inhibitors.
Usually, fragment-based methods follow a knowledge-driven approach, i.e., optimizing a focused set of fragments into
molecular hits.

Expand All @@ -49,10 +49,10 @@ well as back pocket 1 and 2 (B1 and B2), based on defined pocket-spanning residu
Each co-crystallized ligand is fragmented using the BRICS algorithm and its fragments are assigned to the respective
subpocket they occupy.
Following this approach, a fragment library is created with respective subpocket pools. This fragment library enables
an in-depth analysis of the chemical space of known kinase inhibitors, and can be used to enumerate recombined
an in-depth analysis of the chemical space of known kinase inhibitors and can be used to enumerate recombined
fragments in order to generate novel potential inhibitors.

WIP: Custom KinFragLib provides a pipeline to filter the fragments in KinFragLib checking for unwanted substructures (PAINS and Brenk et al.), lead-/drug-likeness (Rule of Three and QED), synthesizability (similarity to buyable building blocks and SYBA) and pairwise retrosynthesizability. Each filter can be (de-)activated and the parameters can be modified by the user to create a customized filtered fragment library.
We have added an extension with *CustomKinFragLib* which provides a pipeline to filter the fragments in KinFragLib checking for unwanted substructures (PAINS and Brenk et al.), lead-/drug-likeness (Rule of Three and QED), synthesizability (similarity to buyable building blocks and SYBA) and pairwise retrosynthesizability. Each filter can be (de-)activated and the parameters can be modified by the user to create a customized filtered fragment library.

## Quick start

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## License

This resource is licensed under the [MIT](https://opensource.org/licenses/MIT) license, a permissive open source license.
This resource is licensed under the [MIT](https://opensource.org/licenses/MIT) license, a permissive open-source license.

## Citation

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# WIP: Custom filtered fragment library
# Custom filtered fragment library

The (full) fragment library resulting from the KinFragLib fragmentation procedure comprises 7486 fragments, which are the basis for exploring the subpocket-based chemical space of ligands co-crystallized with kinases (see `data/fragment_library/`).

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5. Filter for pairwise retrosynthesizability (using ASKCOS) \[optional\]

- `custom_filter_results.csv`: File containing the filtering results, including per fragment, from the pre-filtered library, the SMILES and subpocket as indices, the calculated scores and boolean columns, if a fragment passes a specific filter, generated by the filtering steps.
- `AP.sdf`, `FP.sdf`, `GA.sdf`, `SE.sdf`, `B1.sdf`, and `B2.sdf`: custom filtered fragment library organized by subpocket (as decribed in `data/fragment_library`)

Please refer to the notebook `notebooks/custom_kinfraglib/2_1_custom_filters_pipeline.ipynb` to check how the data was generated and/or to generate your own custom fragment library (de-)activating filters and modifying the filtering parameters.
Please refer to the notebook `notebooks/custom_kinfraglib/2_1_custom_filters_pipeline.ipynb` to check how the data was generated and/or to generate your own custom fragment library (de-)activating filters and modifying the filtering parameters.

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