Experimental and Computational Druggability Exploration of the 14-3-3ζ/SOS1pS1161PPI Interface

The exploration of the druggability of certain protein-protein interactions (PPIs) still remains a challenging task in drug discovery. Here, we present a case study using the 14-3-3-PPI, showing how small molecules can be located that are able to modulate this key oncogenic pathway. A workflow embracing biophysical techniques and MD simulations was developed to evaluate the potential of a 14-3-3ζ PPI system to bind new tool compounds. The significance of the use of computational approaches to compensate for the limitations of experimental techniques is demonstrated. © 2020 American Chemical Society.