Mechanisms of Size Control and Polymorphism in Viral Capsid Assembly

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.

Electrostatic interactions in biological DNA-related systems

“…403 Intrinsic curvature of capsomer-capsomer junctions predisposes the final size of capsids to be formed, while a flexibility of these connections permits the formation of shells of different sizes, e.g. for in vitro capsid assembly around artificial cores 428,429 and polymers. 398 Capsomers of many viruses bear rather high electric charges on their surfaces and contain ionizable groups, 430 that are often distributed quite non-uniformly, see Fig.…”

Mechanisms of kinetic trapping in self-assembly and phase transformation

“…In self-assembly, this is known as "kinetic trapping." In recent years, several studies 4,5,[10][11][12][13][14][15][16][17][18] have observed that self-assembly is most efficient when structures are stabilised by large numbers of relatively weak interactions. In particular, while strong interparticle bonds stabilise the ordered equilibrium state, they are also associated with kinetic trapping effects that frustrate the assembly process.…”

A minimal representation of the self-assembly of virus capsids

“…The simplest models represent the capsomers as isotropic bodies, but they require additional geometrical constraints such as a template of the virus capsid [14][15][16][17][18][19] . In other more complex models each capsomer is represented as a discrete set of either isotropic 17,[20][21][22][23][24] or anisotropic interaction centres [25][26][27] , or as a continuous body of interaction points plus some extra discrete centres 28 .…”