Viral genome structures are optimal for capsid assembly

TL;DR

This study presents a coarse-grained model showing virus capsids assemble optimally around genomes that are negatively overcharged, with structure and electrostatics playing key roles in assembly thermodynamics.

Contribution

The paper introduces a new model demonstrating that electrostatics and NA structure are sufficient to explain capsid assembly and genome length selection, differing from previous models.

Findings

Capsids spontaneously overcharge during assembly.

Optimal genome lengths match natural viral genomes.

NA tertiary structure influences assembly thermodynamics.

Abstract

Understanding how virus capsids assemble around their nucleic acid (NA) genomes could promote efforts to block viral propagation or to reengineer capsids for gene therapy applications. We develop a coarse-grained model of capsid proteins and NAs with which we investigate assembly dynamics and thermodynamics. In contrast to recent theoretical models, we find that capsids spontaneously `overcharge'; i.e., the negative charge of the NA exceeds the positive charge on capsid. When applied to specific viruses, the optimal NA lengths closely correspond to the natural genome lengths. Calculations based on linear polyelectrolytes rather than base-paired NAs underpredict the optimal length, demonstrating the importance of NA structure to capsid assembly. These results suggest that electrostatics, excluded volume, and NA tertiary structure are sufficient to predict assembly thermodynamics and that the ability of viruses to selectively encapsidate their genomic NAs can be explained, at least in part, on a thermodynamic basis.