This repository contains the source code, data, and scripts related to the research on β-hairpin G-loop motifs and minimal G-loop motifs involved in CRBN neosubstrate recognition. This project predicts and validates CRBN-compatible β-hairpin and helical G-loop proteins, contributing to our understanding of molecular glue degraders and their impact on neosubstrate recruitment. This repository reproduces the results of Mining the CRBN Target Space Redefines Rules for Molecular Glue-induced Neosubstrate Recognition (see Reference below).
The scripts in this repository enable mining of G-loop motifs across protein structures derived from PDB and AlphaFold2 models, based on the β-hairpin G-loop around glycine in CK1α. Identified motifs are further processed and validated for CRBN engagement using various biochemical assays.
- Parallelized mining: Efficiently process thousands of structural motifs using the provided Bash script, which parallelizes Python script execution across multiple cores.
- Motif validation: Predictions are filtered based on structural compatibility with CRBN.
- Datasets: Minimal test datasets are included in this repository. The full list of PDB structures are available at zenodo.org/XXX.
To run this code, clone the repository and install the required dependencies:
git clone [email protected]:monterosatx/gloop-mining.git
cd gloop-mining
./build_docker.sh./run_docker.sh
cd {/your/gloop/directory}
./run_test.sh
First download the AF2 and PDB models from zenodo:
Then, run the full list:
./run_all_list.sh
Mining the CRBN Target Space Redefines Rules for Molecular Glue-induced Neosubstrate Recognition
Authors: G. Petzold, P. Gainza, S. Annunziato, I. Lamberto, P. Trenh, L. A. McAllister, B. DeMarco, L. Schwander, R. D. Bunker, M. Zlotosch, R. SriRamaratnam, S. Gilberto, G. Langousis, E. J. Donckele, C. Quan, V. Strande, G. M. De Donatis, S. B. Alabi, J. Alers, M. Matysik, C. Staehly, A. Dubois, A. Osmont, M. Garskovas, D. Lyon, L. Wiedmer, V. Oleinikovas, R. Lieberherr, N. T. Rubin, D. T. Lam, N. I. Widlund, A. Ritzen, R. M. Caceres, D. Vigil, J. Tsai, O. Wallace, M. Peluso, A. Sadok, A. Paterson, V. Zarayskiy, B. Fasching, D. Bonenfant, M. Warmuth, J. Castle, S. A. Townson
bioRxiv 2024.10.07.616933; doi: https://doi.org/10.1101/2024.10.07.616933