RNA-like Polyelectrolyte in a Viral Capsid: Molecular Dynamics with Explicit Electrostatic Interactions

Abstract

The organization of RNA genomes within viral capsids is primarily controlled by electrostatic interactions between the negatively charged genome and positively charged N-terminal domains of coat proteins. In theoretical approaches, these interactions are commonly captured by mean-field models that smooth capsid charge over the inner surface and treat ionic screening as a continuum. However, charges are localized at discrete N-terminal binding sites and ionic screening arises from correlated ion distributions. Here we use molecular dynamics simulations with explicit ions, explicit water, and full Coulomb electrostatics to simulate a linear polyelectrolyte confined within a model capsid bearing discrete N-terminal-like charge sites. We first validate our approach by simulating a polyelectrolyte in bulk solution and demonstrating that persistence length decreases with increasing salt, matching experimental measurements for single-stranded RNA. When confined within a capsid, radial density profiles shift systematically inward from the capsid wall with increasing salt concentration, in agreement with mean-field predictions. By independently varying charge magnitude, binding-site density, and N-terminal protrusion length, we show that total electrostatic coupling governs global organization while geometric details modulate local genome-wall contact and angular genome organization near N-terminals (within the T=3 architecture, linear genome topology, and monovalent salt range studied here). Across all simulations, equilibration times increase sevenfold with salt, revealing kinetic effects inaccessible to equilibrium theory. These results validate continuum approximations for radial organization while revealing deviations arising from discrete molecular details and establishing a framework for future investigations of genome secondary structure, capsid geometry, and assembly kinetics.