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Development and simulation of fully glycosylated molecular models of ACE2-Fc fusion proteins and their interaction with the SARS-CoV-2 spike protein binding domain

We develop fully glycosylated computational models of ACE2-Fc fusion proteins which are promising targets for a COVID-19 therapeutic. These models are tested in their interaction with a fragment of the receptor-binding domain (RBD) of the Spike Protein S of the SARS-CoV-2 virus, via atomistic molecu...

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Autores principales: Bernardi, Austen, Huang, Yihan, Harris, Bradley, Xiong, Yongao, Nandi, Somen, McDonald, Karen A., Faller, Roland
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406073/
https://www.ncbi.nlm.nih.gov/pubmed/32756606
http://dx.doi.org/10.1371/journal.pone.0237295
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author Bernardi, Austen
Huang, Yihan
Harris, Bradley
Xiong, Yongao
Nandi, Somen
McDonald, Karen A.
Faller, Roland
author_facet Bernardi, Austen
Huang, Yihan
Harris, Bradley
Xiong, Yongao
Nandi, Somen
McDonald, Karen A.
Faller, Roland
author_sort Bernardi, Austen
collection PubMed
description We develop fully glycosylated computational models of ACE2-Fc fusion proteins which are promising targets for a COVID-19 therapeutic. These models are tested in their interaction with a fragment of the receptor-binding domain (RBD) of the Spike Protein S of the SARS-CoV-2 virus, via atomistic molecular dynamics simulations. We see that some ACE2 glycans interact with the S fragments, and glycans are influencing the conformation of the ACE2 receptor. Additionally, we optimize algorithms for protein glycosylation modelling in order to expedite future model development. All models and algorithms are openly available.
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spelling pubmed-74060732020-08-13 Development and simulation of fully glycosylated molecular models of ACE2-Fc fusion proteins and their interaction with the SARS-CoV-2 spike protein binding domain Bernardi, Austen Huang, Yihan Harris, Bradley Xiong, Yongao Nandi, Somen McDonald, Karen A. Faller, Roland PLoS One Research Article We develop fully glycosylated computational models of ACE2-Fc fusion proteins which are promising targets for a COVID-19 therapeutic. These models are tested in their interaction with a fragment of the receptor-binding domain (RBD) of the Spike Protein S of the SARS-CoV-2 virus, via atomistic molecular dynamics simulations. We see that some ACE2 glycans interact with the S fragments, and glycans are influencing the conformation of the ACE2 receptor. Additionally, we optimize algorithms for protein glycosylation modelling in order to expedite future model development. All models and algorithms are openly available. Public Library of Science 2020-08-05 /pmc/articles/PMC7406073/ /pubmed/32756606 http://dx.doi.org/10.1371/journal.pone.0237295 Text en © 2020 Bernardi et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Bernardi, Austen
Huang, Yihan
Harris, Bradley
Xiong, Yongao
Nandi, Somen
McDonald, Karen A.
Faller, Roland
Development and simulation of fully glycosylated molecular models of ACE2-Fc fusion proteins and their interaction with the SARS-CoV-2 spike protein binding domain
title Development and simulation of fully glycosylated molecular models of ACE2-Fc fusion proteins and their interaction with the SARS-CoV-2 spike protein binding domain
title_full Development and simulation of fully glycosylated molecular models of ACE2-Fc fusion proteins and their interaction with the SARS-CoV-2 spike protein binding domain
title_fullStr Development and simulation of fully glycosylated molecular models of ACE2-Fc fusion proteins and their interaction with the SARS-CoV-2 spike protein binding domain
title_full_unstemmed Development and simulation of fully glycosylated molecular models of ACE2-Fc fusion proteins and their interaction with the SARS-CoV-2 spike protein binding domain
title_short Development and simulation of fully glycosylated molecular models of ACE2-Fc fusion proteins and their interaction with the SARS-CoV-2 spike protein binding domain
title_sort development and simulation of fully glycosylated molecular models of ace2-fc fusion proteins and their interaction with the sars-cov-2 spike protein binding domain
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406073/
https://www.ncbi.nlm.nih.gov/pubmed/32756606
http://dx.doi.org/10.1371/journal.pone.0237295
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