Mechanisms Of Viral Capsid Assembly Around A Polymer

Abstract

to distinguish from a state of true thermodynamic equilibrium. The pseudo LMA describes partitioning of capsid proteins between assembled capsids and a metastable, supersaturated solution of free proteins. This metastable state decays logarithmically slowly. We show that the line energy of assembly intermediates is the key control parameter of the pseudo LMA.

Encapsulation of a polymer by an icosahedral virus

“…6a below). These observations are consistent with the results of Kivenson et al [60], suggesting that the dependence of assembly outcomes on system parameters does not depend strongly on subunit or capsid geometries. However, the present model enables us to examine the morphologies of failure modes as a function of system parameter values and in the presence of correlated polymer-subunit motions.…”

“…The off-pathway failure modes can be roughly separated into three categories, illustrated by representative snapshots in figure 3b: (1) Uncontained, in which the capsid closes around an incompletely encapsulated polymer. As discussed in Kivenson et al [60], uncontained configurations form when the addition of capsomer subunits and eventual capsid closure is fast compared to polymer incorporation; a large activation barrier hinders complete encapsulation of such configurations. Beyond a certain polymer length, uncontained configurations become thermodynamically favorable (see below).…”

“…Several previous modeling efforts have postulated roles of the RNA in the formation of icosahedral geometries [29, 58] and in enhancing assembly rates [59], but the final structure and assembly pathways were pre-assumed. Recently our group [60] explored capsid assembly around a flexible polymer with a model defined on a cubic lattice, which allowed simulation of large capsid-like cuboidal shells over long time scales. By simulating assembly with a wide range of capsid sizes and polymer lengths, we found that there is an optimal polymer length which maximizes encapsulation yields at finite observation times.…”

“…Depending on polymer length and solution conditions, the simulations predict assembly morphologies that include the polymer completely encapsulated by the icosahedral capsid or non-icosahedral capsules, and several forms of disordered assemblages that fail to completely enclose the polymer. Furthermore, we are able to determine the importance of cooperative subunit-polymer motions, which were poorly supported by the single particle Monte Carlo moves used in [60]. …”

“…[60], but that a different assembly mechanism emerges when the interactions between capsid subunits are very weak and interactions with the polymer are relatively strong. In this mechanism, first hypothesized by McPherson [61] and later by Refs.…”