Viral genome structures are optimal for capsid assembly

Understanding how virus capsids assemble around their nucleic acid (NA) genomes could promote efforts to block viral propagation or to reengineer capsids for gene therapy applications. We develop a coarse-grained model of capsid proteins and NAs with which we investigate assembly dynamics and thermo...

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Main Authors: Jason D Perlmutter, Cong Qiao, Michael F Hagan
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2013-06-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/00632
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author Jason D Perlmutter
Cong Qiao
Michael F Hagan
author_facet Jason D Perlmutter
Cong Qiao
Michael F Hagan
author_sort Jason D Perlmutter
collection DOAJ
description Understanding how virus capsids assemble around their nucleic acid (NA) genomes could promote efforts to block viral propagation or to reengineer capsids for gene therapy applications. We develop a coarse-grained model of capsid proteins and NAs with which we investigate assembly dynamics and thermodynamics. In contrast to recent theoretical models, we find that capsids spontaneously ‘overcharge’; that is, the negative charge of the NA exceeds the positive charge on capsid. When applied to specific viruses, the optimal NA lengths closely correspond to the natural genome lengths. Calculations based on linear polyelectrolytes rather than base-paired NAs underpredict the optimal length, demonstrating the importance of NA structure to capsid assembly. These results suggest that electrostatics, excluded volume, and NA tertiary structure are sufficient to predict assembly thermodynamics and that the ability of viruses to selectively encapsidate their genomic NAs can be explained, at least in part, on a thermodynamic basis.
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spelling doaj.art-a41604a6b2ce41ecaddc73562fd89dc02022-12-22T04:32:37ZengeLife Sciences Publications LtdeLife2050-084X2013-06-01210.7554/eLife.00632Viral genome structures are optimal for capsid assemblyJason D Perlmutter0Cong Qiao1Michael F Hagan2Martin A Fisher School of Physics, Brandeis University, Waltham, United StatesMartin A Fisher School of Physics, Brandeis University, Waltham, United StatesMartin A Fisher School of Physics, Brandeis University, Waltham, United StatesUnderstanding how virus capsids assemble around their nucleic acid (NA) genomes could promote efforts to block viral propagation or to reengineer capsids for gene therapy applications. We develop a coarse-grained model of capsid proteins and NAs with which we investigate assembly dynamics and thermodynamics. In contrast to recent theoretical models, we find that capsids spontaneously ‘overcharge’; that is, the negative charge of the NA exceeds the positive charge on capsid. When applied to specific viruses, the optimal NA lengths closely correspond to the natural genome lengths. Calculations based on linear polyelectrolytes rather than base-paired NAs underpredict the optimal length, demonstrating the importance of NA structure to capsid assembly. These results suggest that electrostatics, excluded volume, and NA tertiary structure are sufficient to predict assembly thermodynamics and that the ability of viruses to selectively encapsidate their genomic NAs can be explained, at least in part, on a thermodynamic basis.https://elifesciences.org/articles/00632virus capsidself assemblyRNA Packaging
spellingShingle Jason D Perlmutter
Cong Qiao
Michael F Hagan
Viral genome structures are optimal for capsid assembly
eLife
virus capsid
self assembly
RNA Packaging
title Viral genome structures are optimal for capsid assembly
title_full Viral genome structures are optimal for capsid assembly
title_fullStr Viral genome structures are optimal for capsid assembly
title_full_unstemmed Viral genome structures are optimal for capsid assembly
title_short Viral genome structures are optimal for capsid assembly
title_sort viral genome structures are optimal for capsid assembly
topic virus capsid
self assembly
RNA Packaging
url https://elifesciences.org/articles/00632
work_keys_str_mv AT jasondperlmutter viralgenomestructuresareoptimalforcapsidassembly
AT congqiao viralgenomestructuresareoptimalforcapsidassembly
AT michaelfhagan viralgenomestructuresareoptimalforcapsidassembly