Unlocking the potential of protein activation has historically posed challenges, necessitating extensive screening and biochemical assays. Dr. Kuen-Phon Wu at the Institute of Biological Chemistry has led a team to demonstrate a paradigm shift. By integrating the advanced deep learning tool, ProteinMPNN, they have engineered ubiquitin into a potent allosteric activator tailored for Rsp5 E3 ligase. The entire process was fully automated from protein designs to sample preparation to functional assays took only three months. This milestone heralds a new era, where AI-driven protein design obviates the need for exhaustive experimental screening and validation. This study has been published in in the journal ACS Synthetic Biology (August 2023).