Switchable Conformation in Protein Subunits: Unveiling Assembly Dynamics of Icosahedral Viruses

The packaging of genetic material within a protein shell called the capsid marks a pivotal step in the life cycle of numerous single-stranded RNA viruses. Understanding how hundreds, or even thousands, of proteins assemble around the genome to form highly symmetrical structures remains an unresolved puzzle. In this paper, we design novel subunits and develop a model that allows us to explore the assembly pathways and genome packaging mechanisms of icosahedral viruses, specifically focusing on the most abundant capsid architecture, $T=3$, which was previously inaccessible. Using molecular dynamics simulations, we observe capsid fragments, varying in protein number and morphology, assembling at different locations along the genome. Initially, these fragments create a disordered structure that later merges to form a highly symmetric capsid. The model proves effective in addressing several longstanding questions about virus assembly. For instance, it enables us to investigate the advantages of RNA packaging by capsid proteins over linear polymers. Our MD simulations align with our experimental findings from small-angle X-ray scattering and cryo-transmission electron microscopy, which explore the assembly products of viral capsid proteins around RNAs with distinct topologies.