Encapsulation of a polymer by an icosahedral virus

Abstract

The coat proteins of many viruses spontaneously form icosahedral capsids around nucleic acids or other polymers. Elucidating the role of the packaged polymer in capsid formation could promote biomedical efforts to block viral replication and enable use of capsids in nanomaterials applications. To this end, we perform Brownian dynamics on a coarse-grained model that describes the dynamics of icosahedral capsid assembly around a flexible polymer. We identify several mechanisms by which the polymer plays an active role in its encapsulation, including cooperative polymer-protein motions. These mechanisms are related to experimentally controllable parameters such as polymer length, protein concentration, and solution conditions. Furthermore, the simulations demonstrate that assembly mechanisms are correlated to encapsulation efficiency, and we present a phase diagram that predicts assembly outcomes as a function of experimental parameters. We anticipate that our simulation results will provide a framework for designing in vitro assembly experiments on single-stranded RNA virus capsids.

Energies and pressures in viruses: contribution of nonspecific electrostatic interactions

“…It seems likely that the spatial inhomogeneity of the capsid charge, obeying the icosahedral symmetry of the capsid, may be responsible for ordering of the ss-RNA molecule 120 that has been observed in several experiments 108,109 , but also in simulations in Ref. 121 . It is also of interest to note that the ssRNA may locally form double stranded RNA hairpins, increasing the binding energy in this way, both via the increase of packing density and occurrence of inter-base hydrogen bonding.…”

“…to bring the total charge of the assembled virus within the borders enabling a spontaneous assembly (Brownian dynamics studies of ssRNA (generic polymer) virus assembly which account for the electrostatic interactions via model pairwise interactions can be found in Ref. 121 ). The electrostatic interactions between the ssRNA and the proteins can thus be viewed as the reason for the characteristic size of the virus 111,230 † † .…”

Thermodynamic basis for the genome to capsid charge relationship in viral encapsidation

“…If the RNA are sufficiently large, and on account of their electrostatic repulsion with each other, the likelihood of multiple RNA nucleating one capsid is low and, for the optimal length question, we may confine ourselves to the population of single RNA-encapsidated viral particles. Also, following previous theoretical works (3,(5)(6)(7)(10)(11)(12)(13)(14)(15), we treat the RNA as a linear polyelectrolyte, and ignore the secondary structures (16). This approximation is in part a computational necessity and in part guided by the motivation to elucidate the generic features of electrostatically driven viral assembly by using simple models.…”

RNA topology remolds electrostatic stabilization of viruses

“…In virtually all theoretical studies published to date investigating the overcharging in viruses, the genome is modeled as a simple linear polyelectrolyte chain [15,[22][23][24]. Thus the phenomenon of overcharging is associated with many factors other than the structure of RNA [14][15][16][17]22].…”