Molecular Dynamics and Intrinsic Disorder Analysis of the SARS-CoV-2 Nsp1 Structural Changes Caused by Substitution and Deletion Mutations

Document Type

Article

Publication Date

2022

Keywords

Sars-cov-2, Nsp1, Mutations, MD Simulation, Intrinsically Disordered Regions

Digital Object Identifier (DOI)

https://doi.org/10.1080/08927022.2022.2075546

Abstract

SARS-CoV-2 non-structural protein 1 (Nsp1) is a virulence factor that inhibits the translation of host mRNAs and interacts with viral RNA. To date, hundreds of mutations (base substitutions, deletions, and insertions) have been reported in SARS-CoV-2 Nsp1. Despite the relevance of Nsp1, a few studies have been conducted to understand the effect of those mutations on Nsp1 structure and function. In this study, the effects of the most frequent mutations were investigated using molecular dynamics simulations. We found that several mutations profoundly affect the local intrinsic disorder predisposition, with most deletions increasing disorder propensity and replacement mutations inducing variable effects. We found that deletions Δ80–90 and Δ156–158 destabilise the protein structure. For example, the Δ156–158 cause a higher root-mean-square deviation (RMSD) and Rg values than those of the wild-type of SARS-CoV-2 Nsp1. We also found that the SARS-CoV-2 Nsp1 is slightly more disordered than its counterpart from SARS-CoV. A better understanding of the complexity and dynamic nature of interactions between intrinsically disordered segments of Nsp1 and ribosome subunits might help develop novel therapeutic countermeasures against the SARS-CoV-2 variants.

Was this content written or created while at USF?

Yes

Citation / Publisher Attribution

Molecular Simulation, v. 48, issue 13, p. 1192-1201

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