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Unveiling the Hidden Rules of Spherical Viruses Using Point Arrays

Since its introduction, the Triangulation number has been the most successful and ubiquitous scheme for classifying spherical viruses. However, despite its many successes, it fails to describe the relative angular orientations of proteins, as well as their radial mass distribution within the capsid....

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Detalles Bibliográficos
Autor principal: Wilson, David P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232142/
https://www.ncbi.nlm.nih.gov/pubmed/32326043
http://dx.doi.org/10.3390/v12040467
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author Wilson, David P.
author_facet Wilson, David P.
author_sort Wilson, David P.
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description Since its introduction, the Triangulation number has been the most successful and ubiquitous scheme for classifying spherical viruses. However, despite its many successes, it fails to describe the relative angular orientations of proteins, as well as their radial mass distribution within the capsid. It also fails to provide any critical insight into sites of stability, modifications or possible mutations. We show how classifying spherical viruses using icosahedral point arrays, introduced by Keef and Twarock, unveils new geometric rules and constraints for understanding virus stability and key locations for exterior and interior modifications. We present a modified fitness measure which classifies viruses in an unambiguous and rigorous manner, irrespective of local surface chemistry, steric hinderance, solvent accessibility or Triangulation number. We then use these point arrays to explain the immutable surface loops of bacteriophage MS2, the relative reactivity of surface lysine residues in CPMV and the non-quasi-equivalent flexibility of the HBV dimers. We then explain how point arrays can be used as a predictive tool for site-directed modifications of capsids. This success builds on our previous work showing that viruses place their protruding features along the great circles of the asymmetric unit, demonstrating that viruses indeed adhere to these geometric constraints.
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spelling pubmed-72321422020-06-01 Unveiling the Hidden Rules of Spherical Viruses Using Point Arrays Wilson, David P. Viruses Article Since its introduction, the Triangulation number has been the most successful and ubiquitous scheme for classifying spherical viruses. However, despite its many successes, it fails to describe the relative angular orientations of proteins, as well as their radial mass distribution within the capsid. It also fails to provide any critical insight into sites of stability, modifications or possible mutations. We show how classifying spherical viruses using icosahedral point arrays, introduced by Keef and Twarock, unveils new geometric rules and constraints for understanding virus stability and key locations for exterior and interior modifications. We present a modified fitness measure which classifies viruses in an unambiguous and rigorous manner, irrespective of local surface chemistry, steric hinderance, solvent accessibility or Triangulation number. We then use these point arrays to explain the immutable surface loops of bacteriophage MS2, the relative reactivity of surface lysine residues in CPMV and the non-quasi-equivalent flexibility of the HBV dimers. We then explain how point arrays can be used as a predictive tool for site-directed modifications of capsids. This success builds on our previous work showing that viruses place their protruding features along the great circles of the asymmetric unit, demonstrating that viruses indeed adhere to these geometric constraints. MDPI 2020-04-20 /pmc/articles/PMC7232142/ /pubmed/32326043 http://dx.doi.org/10.3390/v12040467 Text en © 2020 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wilson, David P.
Unveiling the Hidden Rules of Spherical Viruses Using Point Arrays
title Unveiling the Hidden Rules of Spherical Viruses Using Point Arrays
title_full Unveiling the Hidden Rules of Spherical Viruses Using Point Arrays
title_fullStr Unveiling the Hidden Rules of Spherical Viruses Using Point Arrays
title_full_unstemmed Unveiling the Hidden Rules of Spherical Viruses Using Point Arrays
title_short Unveiling the Hidden Rules of Spherical Viruses Using Point Arrays
title_sort unveiling the hidden rules of spherical viruses using point arrays
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232142/
https://www.ncbi.nlm.nih.gov/pubmed/32326043
http://dx.doi.org/10.3390/v12040467
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