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Most coarse-grained models of individual capsomers associated with viruses employ rigid building blocks that do not exhibit shape adaptation during self-assembly. We develop a coarse-grained general model of viral capsomers that incorporates their stretching and bending energies while retaining many features of the rigid-body models, including an overall trapezoidal shape with attractive interaction sites embedded in the lateral walls to favor icosahedral capsid assembly. Molecular dynamics simulations of deformable capsomers reproduce the rich self-assembly behavior associated with a general T=1 icosahedral virus system in the absence of a genome. Transitions from non-assembled configurations to icosahedral capsids to kinetically-trapped malformed structures are observed as the steric attraction between capsomers is increased. An assembly diagram in the space of capsomer–capsomer steric attraction and capsomer deformability reveals that assembling capsomers of higher deformability into capsids requires increasingly large steric attraction between capsomers. Increasing capsomer deformability can reverse incorrect capsomer–capsomer binding, facilitating transitions from malformed structures to symmetric capsids; however, making capsomers too soft inhibits assembly and yields fluid-like structures.
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From Disorder to Icosahedral Symmetry: How Conformation-Switching Subunits Enable RNA Virus Assembly
Icosahedral capsids are ubiquitous among spherical viruses, yet their assem- bly pathways and governing interactions remain elusive. We present a molecular dynamics model that incorporates essential physical and biological interactions, including protein diffusion, genome flexibility, and a conformational switch that mimics allostery and activates the elastic properties of proteins upon binding. This switch makes the simulations computationally feasible and enables the assembly of icosahedral capsids around a flexible genome—overcoming long-standing lim- itations in previous models. Using this framework, we successfully reproduce the self-assembly of subunits around a flexible genome into icosahedral shells with numbers greater than one – most notably 3, the most common structure in na- ture – a feat that rigid-body models have so far failed to achieve. We systematically explore the range of morphologies formed with different genome architectures, in line with in vitro experiments using cowpea chlorotic mottle virus capsid proteins: viral RNAs with more complex structure form more complete and stable capsids than linear ones. These results provide a predictive framework for genome-guided assembly and capsid design.
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- Award ID(s):
- 2131963
- PAR ID:
- 10632174
- Publisher / Repository:
- Science Advances
- Date Published:
- Journal Name:
- Science advances
- ISSN:
- 2375-2548
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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