From disorder to icosahedral symmetry: How conformation-switching subunits enable RNA virus assembly.

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 <i>T</i> numbers greater than one-most notably <i>T</i> = 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.