diff --git a/README.md b/README.md index 205ea642..fc6c08ba 100644 --- a/README.md +++ b/README.md @@ -27,9 +27,9 @@ This repository holds the following resources: 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 @@ -37,7 +37,7 @@ Please find detailed description of files in `data/` and `notebooks/` in the fol 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. @@ -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 @@ -103,7 +103,7 @@ We are looking forward to hearing from you! ## 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 diff --git a/data/fragment_library_custom_filtered/README.md b/data/fragment_library_custom_filtered/README.md index 6435f28d..56dd4302 100644 --- a/data/fragment_library_custom_filtered/README.md +++ b/data/fragment_library_custom_filtered/README.md @@ -1,4 +1,4 @@ -# 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/`). @@ -11,5 +11,6 @@ To reduce the fragment library size and enable the recombination avoiding combin 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. \ No newline at end of file +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.