Experimental and Computational Druggability Exploration of the 14-3-3ζ/SOS1pS<sup>1161</sup> PPI Interface
Alice Ballone, Francesca Picarazzi, Christine E. Prosser, Jeremy Davis, Christian Ottmann, Mattia Mori
Abstract
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.
Topics & Concepts
DruggabilityWorkflowDrug discoveryComputational biologyKey (lock)Computer scienceInterface (matter)Task (project management)ChemistryBioinformaticsBiologyBiochemistryEngineeringParallel computingDatabaseMaximum bubble pressure methodSystems engineeringGeneBubbleComputer security14-3-3 protein interactionsMicrotubule and mitosis dynamicsFungal and yeast genetics research