Research Highlights
AI Accelerates Protein Design and Enhances Enzyme Activity

Unlocking the potential of protein activation has historically posed challenges, necessitating extensive screening and biochemical assays. Kuen-Phon Wu 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. Published in ACS Synthetic Biology (August 2023), this work underscores the pivotal role of AI tools in revolutionizing biological and biomedical research.

The first authors of this work are research assistants: Hsi-Wen Kao and Wei-Lin Lu. Other authors include IBC specialists Dr. Meng-Ru Ho, Dr. Tzu-Ping Ko, the Wu group members, and Dr. Shang-Te Danny Hsu at IBC.

Article title: Robust Design of Effective Allosteric Activators for Rsp5 E3 Ligase Using the Machine Learning Tool ProteinMPNN

Article link: https://doi.org/10.1021/acssynbio.3c00042

Authors: Kao HW, Lu WL, Ho MR, Lin YF, Hsieh YJ, Ko TP, Hsu STD, Wu KP*