An international research team, including a Korea-based researcher, designed large protein assemblies that self-assemble in a way similar to viruses in nature using artificial intelligence (AI).
The Ministry of Science and ICT said that Lee Sang-min, a professor in the Department of Chemical Engineering at Pohang University of Science and Technology POSTECH, worked with the team of 2024 Nobel chemistry laureate David Baker of the University of Washington to develop a design principle in which a single artificial protein self-assembles into a virus-like structure. The findings were published in Nature on the 21st.
The "protein nanocage" is a hollow structure at the nm (nanometer, one-billionth of a meter) scale formed by multiple proteins binding on their own. Its interior space can hold drugs, genetic material, or enzymes, and its surface can be decorated with substances such as vaccine antigens.
Because of this, protein nanocages have already been continuously evaluated for potential use in vaccine and drug delivery research. For example, ferritin, an iron-storage protein, naturally forms a hollow spherical structure and has been studied as a platform for antigen display or drug loading.
To realize protein nanocages, the team applied "quasi-symmetry" to artificial protein design. Quasi-symmetry is a principle in which the pattern does not repeat in an entirely identical way but forms an overall ordered structure, as seen in viruses in nature.
The team used a trimer—three proteins assembled together—as the basic unit and, using an AI-based protein structure generation tool, designed a new consolidation structure. With this tool, the team designed the consolidation sites so that the proteins would not spread out like a flat sheet but instead close into a rounded, dome-like shell.
The designed proteins were actually produced using Escherichia coli. When their structures were observed with cryo-electron microscopy, the proteins were found to self-assemble into rounded shells ranging from about 70 nm to 220 nm in diameter. The smallest assembly resembled a precise "nano soccer ball."
The team plans follow-up studies to more uniformly control the size of the assemblies by using internal scaffold proteins or nucleic acids as templates. If the size and uniformity of the assemblies can be tuned more precisely, their potential applications are expected to grow in bio and medical fields, including targeted drug delivery, genetic material delivery, and vaccine antigen display.
Professor Lee Sang-min said, "Viruses are a good natural model showing that sophisticated molecular structures can be built without perfect symmetry," adding, "This study confirms that adjusting only the minute angles between protein blocks can change the size and shape of the final assembly."
References
Nature (2026), DOI: https://doi.org/10.1038/s41586-026-10554-z