An international research team led by a South Korean scientist has successfully used artificial intelligence (AI) to design a large-scale protein structure that faithfully reproduces the self-assembly principles found in naturally occurring viruses.
The Ministry of Science, Information and Communications Technology (MSIT) announced that Professor Sangmin Lee of the Pohang University of Science and Technology’s (POSTECH) School of Chemical Engineering, in collaboration with Professor David Baker of the University of Washington (2024 Nobel Prize Laureate in Chemistry), has developed a design principle that allows a single protein component to simultaneously form pentagonal and hexagonal arrays and self-assemble into virus-like structures.
This research was supported by the MSIT program. nature – The world’s most prestigious academic journal – Thursday, May 21st at midnight Korean time.
Protein nanocages: the most promising next-generation drug delivery platform
Protein nanocages have emerged as the most promising materials in the biomedical field for next-generation drug delivery. These are hollow nanometer (nm)-scale structures formed by the spontaneous association of multiple proteins. They can stably transport drugs, genetic material, and enzymes into their internal spaces, and antigens can attach to their outer shell.
However, existing design techniques rely heavily on computationally derived “perfectly symmetrical structures”, severely limiting the size and complexity of structures that can be achieved from a single protein building block.
Replicating nature’s blueprint: quasi-symmetry
In contrast, viruses that exist in nature repeatedly use a single type of protein hundreds to thousands of times, and construct huge shells while delicately adjusting the position of each protein and the local environment. This principle is known as quasi-symmetry, and in this study we have successfully implemented this elegant natural principle into the design of artificial proteins.
The researchers realized that the key to expanding the virus’s shell size lies in the angles and curvatures between the protein components. If the proteins lay too flat, the shell will not close. If the curvature is too large, the structure will be too small. By precisely engineering this balance, the team guided a single protein to simultaneously occupy both pentagonal and hexagonal environments depending on its position within the assembly.
To achieve this, we used trimeric units (clusters of three proteins) as basic building blocks and designed new connected structures using RFdiffusion, an AI-based protein structure generation tool. Similar to stacking connected building blocks at different angles, this approach allowed the proteins to fit into each other in different directions, producing giant dome-shaped shells rather than flat sheets.
Experimental verification using cryo-electron microscopy
The research team used E. coli to produce engineered proteins and observed their morphology using state-of-the-art cryo-electron microscopy. The results confirmed that proteins spontaneously assemble into spherical shells with sizes ranging from a minimum of 70 nm to a maximum of 220 nm. The smallest structure took the shape of an elaborate “nano-soccer ball,” while the largest was more than three times that size.
Significance and future prospects
The study attracted significant attention from the scientific community because it allowed for the freedom to construct large virus-like structures using a single fully AI-designed artificial protein, rather than reusing existing viral proteins. If commercialized, this technology is expected to enable innovative applications across the biomedical field, including targeted drug and genetic material delivery systems and vaccine antigen presentation platforms. Follow-up studies are also planned to use internal scaffold proteins or nucleic acids as templates to achieve more uniform size control.
Additionally, related research on artificial protein structures led by Professor Baker and Professor Sangmin Lee as co-authors nature on the same day.
This makes Professor Sangmin Lee the corresponding author of one paper and the co-author of another published in one of the world’s leading scientific journals, a remarkable and rare accomplishment.
Researcher’s comments
Viruses are nature’s best example of how perfect symmetry is not the only path to sophisticated molecular structures. ”
Professor Sangmin Lee of POSTECH
He explained that just as subtle changes in the angles between molecular tiles can turn a plane into a giant dome, this study shows that by precisely controlling the geometry of local protein blocks, the size and shape of the final assembly can be fine-tuned.
“This achievement is a remarkable demonstration of the world-class basic research capabilities of Korea’s leading scientists, achieved through collaboration with Nobel laureates,” said Kim Sung-soo, director of research and development policy at MSIT. He added, “MSIT will continue to provide unwavering support to improve the research capabilities of Korean scientists and produce globally pioneering results.”
sauce:
Pohang University of Science and Technology (POSTECH)
Reference magazines:
Lee, S. Others. (2026). Design of one-component quasisymmetric protein nanocages. nature. DOI: 10.1038/s41586-026-10554-z. https://www.nature.com/articles/s41586-026-10554-z
