The journal Nature recently reported on synthetic calcium ion channels designed from scratch by artificial intelligence. This research, completed at the Institute for Protein Design at the University of Washington School of Medicine, demonstrates the feasibility of constructing transmembrane proteins with specific functions through computational means.

Biochemistry professor David Baker stated: "Biochemists have been studying ion channels for decades, and debates about how they work have been almost as long. We set out to build new versions so that biologists can precisely control cell signaling." The research team used the RFdiffusion artificial intelligence program, starting from the selective filter structure, to gradually construct complete channel proteins capable of specifically conducting calcium ions.

Similar to naturally occurring calcium channels on the membranes of nerve cells and muscle cells, this synthetic channel can regulate the flow of calcium ions, thereby affecting electrical signal conduction. The primary completer of the research, postdoctoral researcher Liu Yuxin, explained: "By building channels that can be precisely controlled, we hope to study and ultimately manipulate cell behavior in entirely new ways." The team successfully generated amino acid sequences that can stably exist in lipid bilayers by adjusting the design tools.

The researchers expressed the designed calcium channels in insect cells and used patch-clamp technology for functional validation. Experimental results showed that multiple designed channels could effectively conduct calcium ions, with selectivity for calcium ions reaching five times that of sodium ions. Cryo-electron microscopy three-dimensional structure analysis confirmed that the atomic-level structure of the synthetic channels highly matched the computational models.

This research method provides a new approach for in-depth exploration of the selectivity mechanisms of ion channels. The research team plans to continue using this design strategy to systematically study the physical principles of metal ion transport through membrane proteins, which are of great significance for understanding processes such as neural signal transmission and immune cell activation.