Icosahedral capsid formation by capsomers and short polyions

Abstract

Kinetical and structural aspects of the capsomer-polyion co-assembly into icosahedral viruses have been simulated by molecular dynamics using a coarse-grained model comprising cationic capsomers and short anionic polyions. Conditions were found at which the presence of polyions of a minimum length was necessary for capsomer formation. The largest yield of correctly formed capsids was obtained at which the driving force for capsid formation was relatively weak. Relatively stronger driving forces, i.e., stronger capsomer-capsomer short-range attraction and∕or stronger electrostatic interaction, lead to larger fraction of kinetically trapped structures and aberrant capsids. The intermediate formation was investigated and different evolving scenarios were found by just varying the polyion length.

The Assembly Pathway of an Icosahedral Single-Stranded RNA Virus Depends on the Strength of Inter-Subunit Attractions

“…Multiplet structures are not unique to CCMV and have been reported to occur in the in vitro assembly of turnip crinkle virus [20] under “conditions that favor assembly so strongly that they lock in’ mistakes”, as well as for bacteriophage fr [28] when the RNA packaged was significantly longer than the viral genome. While the mechanism of multiplet formation has not been established experimentally, coarse-grained simulations [26,29] suggest that it is a form of kinetic trapping resulting from strong CP–CP attraction—consistent with our experimental observations and with other kinetic–thermodynamic models [30,31]. …”

Mechanisms of Virus Assembly

“…spontaneous curvature, section 4.1) and stoichiometry (76, 87). For RNA significantly below optimal length, multiple RNAs were packaged in each capsid (108, 113), as seen in coarse-grained dynamics simulations with short linear polyelectrolytes (111). In the experiments, capsid formation required equilibrium between multiple disordered protein-RNA complexes, leading to highly cooperative assembly (113).…”

Assembled viral-like nanoparticles from elastic capsomers and polyion

“…19 The viral genome has been treated as a flexible polymer or polyion chains with specific interactions, whereas the capsomer model, initially proposed by and later adopted by Mahalik and Muthukumar, 23 Zhang and Linse, 24,25 Zhang et al 26 Hagan and Zandi, 8 Perlmutter et al, 27 and Elrad and Hagan, 28 retained three prominent features for describing the virus formation. First, the coarse-grained building block representing a capsomer translates and rotates as a rigid body whose asymmetric shape is compatible with the icosahedral symmetry of the capsid, the choices being the triangular, [23][24][25][26]28 trapezoidal, [20][21][22] or pentagonal shape. 6,8,27,29 Second, the curvature allowing assembly toward the interior is obtained by designing truncated-pyramidal building block consisting of several layers of subunits.…”

“…6,8,27,29 Second, the curvature allowing assembly toward the interior is obtained by designing truncated-pyramidal building block consisting of several layers of subunits. [23][24][25][26] Third, the required capsomer wedge in reaching the final icosahedral structure is obtained by enabling the right inclination angle of the lateral sides of the capsomer to the surface normal. [23][24][25] An alternative option to construct the preferred curvature of the capsomer is to consider a single layer of subunits making the building block and "top" pseudo-atoms whose pair-interactions favor the wedge between two attached capsomers consistent with a dodecahedral 6,27 or an icosahedral 28,30 capsid.…”