Controlling viral capsid assembly with templating

Abstract

We develop coarse-grained models that describe the dynamic encapsidation of functionalized nanoparticles by viral capsid proteins. We find that some forms of cooperative interactions between protein subunits and nanoparticles can dramatically enhance rates and robustness of assembly, as compared to the spontaneous assembly of subunits into empty capsids. For large core-subunit interactions, subunits adsorb onto core surfaces en masse in a disordered manner, and then undergo a cooperative rearrangement into an ordered capsid structure. These assembly pathways are unlike any identified for empty capsid formation. Our models can be directly applied to recent experiments in which viral capsid proteins assemble around the functionalized inorganic nanoparticles [Sun et al., Proc. Natl. Acad. Sci (2007) 104, 1354. In addition, we discuss broader implications for understanding the dynamic encapsidation of single-stranded genomic molecules during viral replication and for developing multicomponent nanostructured materials.

A theory for viral capsid assembly around electrostatic cores

“…Prior theoretical works have led to important insights about assembly around polymeric cores but were equilibrium studies [36][37][38][39][40][41] or considered specific RNA-mediated assembly pathways with phenomenological descriptions of proteinnucleic acid interactions. 42,43 Computer simulations of a model in which subunits assemble around rigid spherical cores 44,45 suggest that a core with a geometry commensurate with the lowest free energy empty-capsid morphology can increase assembly rates and the efficiency of assembly ͑com-pared to empty capsid assembly [46][47][48][49][50][51][52][53][54][55][56] ͒ through the effects of heterogeneous nucleation and templating; however, assembly is frustrated for core-subunit interaction strengths that are too strong. 44 Cores that are not size matched with the lowest free energy capsid morphology can direct assembly into alternative capsid morphologies for moderate core-subunit interaction strengths.…”

“…Effective packaging even occurs at a binding free energy g b = 0, showing that assembly on cores can occur under conditions for which spontaneous empty-capsid assembly is not favorable, as seen in experiments 24 and simulations. 44,45 On core surfaces nanoparticle-subunit electrostatic interactions and attractive subunit-subunit interactions overcome subunitsubunit electrostatic repulsions to drive assembly ͓g H = −15.6 kcal/ mol per subunit for g b = 0, Eq. ͑1͔͒.…”

Unlocking Internal Prestress from Protein Nanoshells

“…Because of their robust assembly and regular icosahedral symmetry, spherical viral capsids have been an ideal system for exploring the physical principles governing macromolecular assembly. Coarsegrained molecular dynamics studies have shown that icosahedral capsid assembly can be successfully simulated through precise design of subunit interfaces and local assembly rules for smaller viruses [4][5][6][7]. However, as capsid size and the number of units grows, assembly simulations suffer a "closure catastrophy," becoming kinetically trapped in "monster particle" states, i.e., misassembled aggregates and open shells [5].…”

Optimal architectures of elongated viruses

“…Recently, significant progress has been made in understanding the physical and geometrical principles governing the architecture of in vivo-and in vitro-reconstituted quasispherical viruses (10)(11)(12)(13)(14)(15)(16). Structures of a large number of spherical viruses have been examined in detail for several years (17)*, but the precise geometry and architecture of many nonspherical viruses, in particular those with prolate shapes, have not yet been fully understood.…”