Mechanisms of Size Control and Polymorphism in Viral Capsid Assembly

TL;DR

This paper uses simulations to explore how viral capsids assemble into different shapes and sizes, revealing mechanisms for adaptive assembly and the importance of interaction strength.

Contribution

It introduces a simulation framework that explains size control and polymorphism in viral capsid assembly, aligning with recent experimental findings.

Findings

Adaptive cargo encapsidation depends on moderate interaction strengths.

Stronger interactions hinder assembly by stabilizing incompatible intermediates.

Capsids maintain subunit conformational order even with minimal energetic bias.

Abstract

We simulate the assembly dynamics of icosahedral capsids from subunits that interconvert between different conformations (or quasi-equivalent states). The simulations identify mechanisms by which subunits form empty capsids with only one morphology but adaptively assemble into different icosahedral morphologies around nanoparticle cargoes with varying sizes, as seen in recent experiments with brome mosaic virus (BMV) capsid proteins. Adaptive cargo encapsidation requires moderate cargo-subunit interaction strengths; stronger interactions frustrate assembly by stabilizing intermediates with incommensurate curvature. We compare simulation results to experiments with cowpea chlorotic mottle virus empty capsids and BMV capsids assembled on functionalized nanoparticles and suggest new cargo encapsidation experiments. Finally, we find that both empty and templated capsids maintain the precise spatial ordering of subunit conformations seen in the crystal structure even if interactions that preserve this arrangement are favored by as little as the thermal energy, consistent with experimental observations that different subunit conformations are highly similar.