Core Insights - The article discusses the significant advancements in the field of protein design, particularly focusing on light-responsive proteins and the challenges associated with their de novo design [5][6][12]. Group 1: Research Development - On August 28, 2025, a team from West Lake University published a study in Nature Chemistry, detailing the de novo design of light-responsive protein-protein interactions, enabling reversible formation of protein assemblies [3]. - The research developed a protein docking program suitable for non-natural amino acids, integrating light-responsive non-natural amino acid AzoF with codon expansion technology to design a series of reversible light-responsive proteins [3][7]. Group 2: Challenges in Protein Design - Despite advancements, a major challenge remains in programming new proteins to respond to environmental stimuli and switch between different structural states, which is crucial for precise control of their structure and function [5][6]. - Natural light-responsive proteins have limitations, such as the need for continuous light exposure, long reverse process times, and complex folding, making them difficult to express and apply in heterologous systems [6]. Group 3: Innovations and Applications - The research team successfully designed a variety of protein complexes, including light-responsive homopolymeric and heterodimeric proteins, demonstrating excellent light-responsive characteristics [7][8]. - The heterodimer LRD-7 showed a remarkable affinity change of 167 times in response to light, and the designed proteins exhibited strong thermal stability, maintaining their secondary structure even after heating to 95°C [8]. - The study also explored the creation of light-responsive protein hydrogels and the use of heterodimeric proteins to control gene expression signals [10][12]. Group 4: Future Implications - This research not only resulted in a series of de novo designed light-responsive proteins but also provided new methods and ideas for the design of light-controlled protein-protein interactions, laying a solid foundation for future developments in light-responsive target-binding proteins and molecular machines [12].