INS10-0501
Design of protein nanocages using programmed symmetry breaking
Topic
S10. AI-assisted Design and Simulation of Polymers
When and Where
Sep 29, 2026
17:05 - 17:30
Room 109
Session Chairs
Jian JIANG
Presenter(s)
Sangmin Lee (Pohang University of Science and Technology (POSTECH))
Co-Author(s)
Abstract
Protein nanocages are promising platforms for vaccine design, biologics delivery, and synthetic nanomaterials, but conventional point-group symmetric assemblies are limited in size and complexity. Inspired by viral symmetry breaking and quasisymmetry, we developed design strategies to generate higher triangulation number and quasisymmetric protein cages. Pseudosymmetrization of trimeric building blocks enabled T = 4 tetrahedral, octahedral, and icosahedral cages containing 48, 96, and 240 subunits. In parallel, programmed curvature combined with parametric cage modeling and RFdiffusion generated large quasisymmetric assemblies, including T = 3 to T = 36 cages with 180 to 2160 subunits and diameters up to 220 nm. Electron microscopy and cryo-EM confirmed the designed architectures and revealed how local interface symmetry breaking drives global penton and hexon formation. These results establish a general framework for designing complex protein nanocages for multivalent antigen display, targeted delivery, and biomolecular materials.
