The School of Chemistry and Molecular Engineering at Peking University, the research group of Professor Chen Peng from the Peking University Tsinghua Joint Center for Life Sciences, and the research group of Professor Wang Chu have developed a protein activation technology that integrates "machine learning and biological orthogonal shear reaction" through continuous and in-depth cooperation, achieving a breakthrough in the "near cage" strategy from live cells to live animals. The related achievements were recently published online in the international academic journal Cell under the title "General Strategy for Protein Activation Assisted by Machine Learning". Orthogonal biological reactions refer to chemical reactions that can occur within living organisms but do not interfere with normal biological processes. The development of such reactions not only broadens the biological application boundaries of traditional organic chemical reactions, but also introduces the logic of synthetic chemistry into the study of life systems, revolutionizing the molecular analysis and precise regulation of life processes, and providing a new perspective for revealing complex physiological and pathological mechanisms. ”Chen Peng stated that orthogonal biological reactions, represented by "click chemistry," effectively solve key scientific problems such as in situ labeling and enrichment in complex life systems. However, this chemical reaction mode still has limitations and is difficult to regulate and analyze the functions of biomolecules. Chen Peng introduced that this study, driven by the fusion of machine learning and orthogonal shear reaction in biology, has obtained an innovative protein in situ activation platform technology that can instantly activate the function of target proteins in live animals and precisely regulate protein-protein interactions. This new technology can also achieve precise regulation of cell phenotype, induce apoptosis of tumor cells, and enhance anti-tumor immune response. It can be said that this new technology has propelled the orthogonal cleavage reaction of biology into a new era of 'arbitrary protein+in vivo application', marking an important breakthrough in the development of in vivo chemical reactions. It not only provides a powerful tool for in situ research of dynamic biological processes, but also opens up new avenues for on-demand precision therapy. "Chen Peng told reporters that this study further demonstrates the effectiveness and universality of the combination of machine learning and structural modeling methods in expanding enzyme substrate spectra, and is expected to equip various protein machines with 'control switches' to activate protein functions as needed in live animals, enhance anti-tumor immune response, and promote disease mechanism research and targeted therapy strategy development. (New Society)