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Simulations of Phage T7 Capsid Expansion Reveal the Role of Molecular Sterics on Dynamics
Molecular dynamics techniques provide numerous strategies for investigating biomolecular energetics, though quantitative analysis is often only accessible for relatively small (frequently monomeric) systems. To address this limit, we use simulations in combination with a simplified energetic model t...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695174/ https://www.ncbi.nlm.nih.gov/pubmed/33171826 http://dx.doi.org/10.3390/v12111273 |
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author | Whitford, Paul C. Jiang, Wen Serwer, Philip |
author_facet | Whitford, Paul C. Jiang, Wen Serwer, Philip |
author_sort | Whitford, Paul C. |
collection | PubMed |
description | Molecular dynamics techniques provide numerous strategies for investigating biomolecular energetics, though quantitative analysis is often only accessible for relatively small (frequently monomeric) systems. To address this limit, we use simulations in combination with a simplified energetic model to study complex rearrangements in a large assembly. We use cryo-EM reconstructions to simulate the DNA packaging-associated 3 nm expansion of the protein shell of an initially assembled phage T7 capsid (called procapsid or capsid I). This is accompanied by a disorder–order transition and expansion-associated externalization displacement of the 420 N-terminal tails of the shell proteins. For the simulations, we use an all-atom structure-based model (1.07 million atoms), which is specifically designed to probe the influence of molecular sterics on dynamics. We find that the rate at which the N-terminal tails undergo translocation depends heavily on their position within hexons and pentons. Specifically, trans-shell displacements of the hexon E subunits are the most frequent and hexon A subunits are the least frequent. The simulations also implicate numerous tail translocation intermediates during tail translocation that involve topological traps, as well as sterically induced barriers. The presented study establishes a foundation for understanding the precise relationship between molecular structure and phage maturation. |
format | Online Article Text |
id | pubmed-7695174 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76951742020-11-28 Simulations of Phage T7 Capsid Expansion Reveal the Role of Molecular Sterics on Dynamics Whitford, Paul C. Jiang, Wen Serwer, Philip Viruses Article Molecular dynamics techniques provide numerous strategies for investigating biomolecular energetics, though quantitative analysis is often only accessible for relatively small (frequently monomeric) systems. To address this limit, we use simulations in combination with a simplified energetic model to study complex rearrangements in a large assembly. We use cryo-EM reconstructions to simulate the DNA packaging-associated 3 nm expansion of the protein shell of an initially assembled phage T7 capsid (called procapsid or capsid I). This is accompanied by a disorder–order transition and expansion-associated externalization displacement of the 420 N-terminal tails of the shell proteins. For the simulations, we use an all-atom structure-based model (1.07 million atoms), which is specifically designed to probe the influence of molecular sterics on dynamics. We find that the rate at which the N-terminal tails undergo translocation depends heavily on their position within hexons and pentons. Specifically, trans-shell displacements of the hexon E subunits are the most frequent and hexon A subunits are the least frequent. The simulations also implicate numerous tail translocation intermediates during tail translocation that involve topological traps, as well as sterically induced barriers. The presented study establishes a foundation for understanding the precise relationship between molecular structure and phage maturation. MDPI 2020-11-07 /pmc/articles/PMC7695174/ /pubmed/33171826 http://dx.doi.org/10.3390/v12111273 Text en © 2020 by the authors. 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 Whitford, Paul C. Jiang, Wen Serwer, Philip Simulations of Phage T7 Capsid Expansion Reveal the Role of Molecular Sterics on Dynamics |
title | Simulations of Phage T7 Capsid Expansion Reveal the Role of Molecular Sterics on Dynamics |
title_full | Simulations of Phage T7 Capsid Expansion Reveal the Role of Molecular Sterics on Dynamics |
title_fullStr | Simulations of Phage T7 Capsid Expansion Reveal the Role of Molecular Sterics on Dynamics |
title_full_unstemmed | Simulations of Phage T7 Capsid Expansion Reveal the Role of Molecular Sterics on Dynamics |
title_short | Simulations of Phage T7 Capsid Expansion Reveal the Role of Molecular Sterics on Dynamics |
title_sort | simulations of phage t7 capsid expansion reveal the role of molecular sterics on dynamics |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695174/ https://www.ncbi.nlm.nih.gov/pubmed/33171826 http://dx.doi.org/10.3390/v12111273 |
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