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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Bibliographic Details
Published inbioRxiv
Main Authors Bernardi, Austen, Huang, Yihan, Harris, Bradley S, Xiong, Yongao, Nandi, Somen, Mcdonald, Karen A, Faller, Roland
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 16.07.2020
Subjects
ACE2
Algorithms
Angiotensin-converting enzyme 2
Computer applications
COVID-19
Fc receptors
Glycosylation
Mathematical models
Molecular modelling
Polysaccharides
Protein S
Proteins
Severe acute respiratory syndrome coronavirus 2
Spike protein
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Summary: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. Competing Interest Statement The authors have declared no competing interest. Footnotes * Simulations extended to 75 ns * https://doi.org/10.25338/B82G9B
DOI:10.1101/2020.05.05.079558