Physical Ingredients Controlling Stability and Structural Selection of Empty Viral Capsids

Abstract

One of the crucial steps in the viral replication cycle is the self-assembly of its protein shell. Typically, each native virus adopts a unique architecture, but the coat proteins of many viruses have the capability to self-assemble in vitro into different structures by changing the assembly conditions. However, the mechanisms determining which of the possible capsid shapes and structures is selected by a virus are still not well-known. We present a coarse-grained model to analyze and understand the physical mechanisms controlling the size and structure selection in the assembly of empty viral capsids. Using this model and Monte Carlo simulations, we have characterized the phase diagram and stability of T = 1,3,4,7 and snub cube shells. In addition, we have studied the tolerance of different shells to changes in physical parameters related to ambient conditions, identifying possible strategies to induce misassembly or failure. Finally, we discuss the factors that select the shape of a capsid as spherical, faceted, elongated, or decapsidated. Our model sheds important light on the ingredients that control the assembly and stability of viral shells. This knowledge is essential to get capsids with well-defined size and structure that could be used for promising applications in medicine or bionanotechnology.

Spontaneous non-canonical assembly of CcmK hexameric components from β-carboxysome shells of cyanobacteria

“…recently defined energetic regimes and conditions that lead to empty or cargo-filled BMC [ 31 ]. In our model, hexamers were represented as nearly spherical beads interacting with a simple potential that included: a short-range repulsion term that prevents hexamer collapse; an attraction term driving the assembly; bending and torsion terms accounting for the preferred angle of interaction between hexamers and the energetic cost of bending and twisting them from the optimal angle (more details are provided as M&M and ref [ 45 ]). Based on this model, Brownian dynamics simulations successfully reproduced the formation of assembled patches of CcmK1.…”

“…The interaction between hexamers is modeled using the same potential as in Ref. [ 45 ], which depends on three main parameters: the binding energy between hexamers, ϵ 0 ; the preferred angle of the inter-hexamer interaction, ν ; and the local bending stiffness dictated by α . The interaction between an hexamer and the substrate was modeled using a potential where z is the vertical distance to the substrate, σ s = σ /2 is the equilibrium distance, ϵ s is the adhesion strength and θ i is the polar angle of the orientation of hexamer i.…”

The Missing Tailed Phages: Prediction of Small Capsid Candidates

“…There are several interrelated scientific observations that make the lack of small icosahedral capsids striking among tailed phages. First, T = 1 and T = 3 icosahedral capsid architectures are optimal thermodynamic configurations for protein shells and are the most kinetically favorable icosahedral capsids [13,[24][25][26][27]. T = 1 and T = 3 are the most common architectures imaged among viruses [15].…”

Viral nanomechanics with a virtual atomic force microscope

“…Although the interactions between individual proteins are presumably very complex, the effective capsomer-capsomer interactions are expected to be simpler and more isotropic. Accordingly, our model [53] is coarse-grained at the level of capsomers, i.e. pentamers and hexamers, which are the basic structural units of a viral shell.…”

“…Finally, a nice characteristic of the model is that the interaction parameters can be connected to elastic modulus in the continuum limit. In particular, the 2D Young's modulus is approximately given by [53]…”