From disorder to icosahedral symmetry: How conformation-switching subunits enable RNA virus assembly
Siyu Li, Guillaume Tresset, Roya Zandi
Abstract
Icosahedral capsids are ubiquitous among spherical viruses, yet their assembly pathways and governing interactions remain elusive. We present a molecular dynamics model that incorporates essential physical and biological features, including protein diffusion, genome flexibility, and a conformational switch that mimics allostery and activates the elastic properties of proteins upon binding. This switch makes the simulations computationally feasible, overcoming long-standing limitations of previous models. Using this framework, we successfully reproduce the self-assembly of subunits into icosahedral shells with T numbers greater than one—most notably T = 3, the most common structure in nature—a feat rigid-body models have so far failed to achieve. We also examine how genome architecture influences assembly and observe trends consistent with experiments using cowpea chlorotic mottle virus proteins: RNAs with more complex structure yield more complete capsids than do linear ones. These results establish a predictive framework for genome-guided assembly and offer insight into designing synthetic capsids for biomedical applications.