Mutations in fragment site of SACK1G abolish interaction with CK1α

This repository includes the code and results of the computational analysis of our pre-print "Mutations within the predicted fragment-binding region of FAM83G/SACK1G abolish its interaction with the Ser/Thr kinase CK1α", which can be found here.

Directories

Within the AFDB_FAM83B_model and AFDB_FAM83G_model directories, the AlphaFold DB models for human SACK1B (Q5T0W9) and SACK1G (A6ND36) can be found, respectively.

The FAM83B_FRAGSYS directory includes the necessary data from the FRAGSYS [1] analysis of FAM83B/SACK1B, which was employed to hightlight the most likely sites to affect SACK1B function as well as the individual residues within them.

The FAM83G_SS_prediction_JPRED directory include JPred [2] secondary structure predictions for FAM83G/SACK1G employed to complement secondary structure assignments from the AlphaFold [3]three-dimensional structure models.

The FAM83_dimers directory includes the 3D structure models obtained in this work using the Colabfold v1.5.2 [4] implementation of AlphaFold Multimer v3 [5].

Finally, the notebooks directory includes the two Jupyter notebooks employed to carry out the computational analysis described in our manuscript.

Dependencies

• Colabfold
• Matplotlib
• Numpy
• Pandas
• Seaborn

References

1. Utgés, J.S., MacGowan, S.A., Ives, C.M. et al. Classification of likely functional class for ligand binding sites identified from fragment screening. Commun. Biol. 7, 320 (2024). https://doi.org/10.1038/s42003-024-05970-8
2. Alexey Drozdetskiy, Christian Cole, James Procter, Geoffrey J. Barton, JPred4: a protein secondary structure prediction server, Nucleic Acids Res., Volume 43, Issue W1, 1 July 2015, Pages W389–W394, https://doi.org/10.1093/nar/gkv332
3. Jumper, J., Evans, R., Pritzel, A. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021). https://doi.org/10.1038/s41586-021-03819-2
4. Mirdita, M., Schütze, K., Moriwaki, Y. et al. ColabFold: making protein folding accessible to all. Nat. Methods 19, 679–682 (2022). https://doi.org/10.1038/s41592-022-01488-1
5. Abramson, J., Adler, J., Dunger, J. et al. Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature 630, 493–500 (2024). https://doi.org/10.1038/s41586-024-07487-w