Computational Study of Helicase from SARS-CoV-2 in RNA-Free and Engaged Form
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the pandemic that broke out in 2020 and continues to be the cause of massive global upheaval. Coronaviruses are positive-strand RNA viruses with a genome of ~30 kb. The genome is replicated and transcribed by RNA-...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/23/14721 |
| _version_ | 1797463175416774656 |
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| author | Francesca Di Matteo Giorgia Frumenzio Balasubramanian Chandramouli Alessandro Grottesi Andrew Emerson Francesco Musiani |
| author_facet | Francesca Di Matteo Giorgia Frumenzio Balasubramanian Chandramouli Alessandro Grottesi Andrew Emerson Francesco Musiani |
| author_sort | Francesca Di Matteo |
| collection | DOAJ |
| description | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the pandemic that broke out in 2020 and continues to be the cause of massive global upheaval. Coronaviruses are positive-strand RNA viruses with a genome of ~30 kb. The genome is replicated and transcribed by RNA-dependent RNA polymerase together with accessory factors. One of the latter is the protein helicase (NSP13), which is essential for viral replication. The recently solved helicase structure revealed a tertiary structure composed of five domains. Here, we investigated NSP13 from a structural point of view, comparing its RNA-free form with the RNA-engaged form by using atomistic molecular dynamics (MD) simulations at the microsecond timescale. Structural analyses revealed conformational changes that provide insights into the contribution of the different domains, identifying the residues responsible for domain–domain interactions in both observed forms. The RNA-free system appears to be more flexible than the RNA-engaged form. This result underlies the stabilizing role of the nucleic acid and the functional core role of these domains. |
| first_indexed | 2024-03-09T17:46:57Z |
| format | Article |
| id | doaj.art-e7041eb08d4d43f98896a3cf36ebffbd |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:46:57Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e7041eb08d4d43f98896a3cf36ebffbd2023-11-24T11:06:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123231472110.3390/ijms232314721Computational Study of Helicase from SARS-CoV-2 in RNA-Free and Engaged FormFrancesca Di Matteo0Giorgia Frumenzio1Balasubramanian Chandramouli2Alessandro Grottesi3Andrew Emerson4Francesco Musiani5Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology, University of Bologna, Viale G. Fanin 40, 40127 Bologna, ItalySuper Computing Applications and Innovation, Department HPC, CINECA, via Magnanelli 6/3, 40033 Casalecchio di Reno, ItalySuper Computing Applications and Innovation, Department HPC, CINECA, via Magnanelli 6/3, 40033 Casalecchio di Reno, ItalyDepartment HPC, CINECA, via dei Tizii 6, 00185 Roma, ItalySuper Computing Applications and Innovation, Department HPC, CINECA, via Magnanelli 6/3, 40033 Casalecchio di Reno, ItalyLaboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology, University of Bologna, Viale G. Fanin 40, 40127 Bologna, ItalySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the pandemic that broke out in 2020 and continues to be the cause of massive global upheaval. Coronaviruses are positive-strand RNA viruses with a genome of ~30 kb. The genome is replicated and transcribed by RNA-dependent RNA polymerase together with accessory factors. One of the latter is the protein helicase (NSP13), which is essential for viral replication. The recently solved helicase structure revealed a tertiary structure composed of five domains. Here, we investigated NSP13 from a structural point of view, comparing its RNA-free form with the RNA-engaged form by using atomistic molecular dynamics (MD) simulations at the microsecond timescale. Structural analyses revealed conformational changes that provide insights into the contribution of the different domains, identifying the residues responsible for domain–domain interactions in both observed forms. The RNA-free system appears to be more flexible than the RNA-engaged form. This result underlies the stabilizing role of the nucleic acid and the functional core role of these domains.https://www.mdpi.com/1422-0067/23/23/14721SARS-CoV-2NSP13helicaseRNAmolecular dynamicsHPC |
| spellingShingle | Francesca Di Matteo Giorgia Frumenzio Balasubramanian Chandramouli Alessandro Grottesi Andrew Emerson Francesco Musiani Computational Study of Helicase from SARS-CoV-2 in RNA-Free and Engaged Form International Journal of Molecular Sciences SARS-CoV-2 NSP13 helicase RNA molecular dynamics HPC |
| title | Computational Study of Helicase from SARS-CoV-2 in RNA-Free and Engaged Form |
| title_full | Computational Study of Helicase from SARS-CoV-2 in RNA-Free and Engaged Form |
| title_fullStr | Computational Study of Helicase from SARS-CoV-2 in RNA-Free and Engaged Form |
| title_full_unstemmed | Computational Study of Helicase from SARS-CoV-2 in RNA-Free and Engaged Form |
| title_short | Computational Study of Helicase from SARS-CoV-2 in RNA-Free and Engaged Form |
| title_sort | computational study of helicase from sars cov 2 in rna free and engaged form |
| topic | SARS-CoV-2 NSP13 helicase RNA molecular dynamics HPC |
| url | https://www.mdpi.com/1422-0067/23/23/14721 |
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