Satellite Tobacco Mosaic Virus: Revealing Environmental Drivers of Capsid and Nucleocapsid Stability using High-Resolution Simulations

Satellite tobacco mosaic virus (STMV) is a model system for studying viral assembly and stability due to its architecture: a single-stranded RNA genome enclosed in an icosahedral capsid. Coupling a polarizable force-field to enhanced sampling, we explored at high-resolution the long-timescale structural dynamics of a complete ∼1M-atom STMV. RNA-free capsids exhibit remarkable stability at physiological salt concentrations, suggesting an evolutionary adaptation for capsid reuse during the viral life cycle. This observation challenges the notion that empty capsids are exclusively products of abortive assembly, positioning them instead as functional intermediates in viral reproduction. Additionally, RNA encapsidation creates electrostatic dependencies that magnesium ions mitigate, stabilizing both RNA and capsid through long-residence-time interactions with phosphate groups. Chloride ions further influence capsid permeability by modulating salt-bridge disruptions and interprotomeric interactions, with these effects being pH-dependent: enhanced at pH < 7, preserving nucleocapsid integrity, or weakened at pH = 7, facilitating disassembly and RNA release.