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Molecular Dynamics Studies on the Structural Characteristics for the Stability Prediction of SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the COVID-19 pandemic in the world. The spike protein of the various proteins encoded in SARS-CoV-2 binds to human ACE2, fuses, and enters human cells in the respiratory system. Spike protein, however, is highly variable, and many...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395978/ https://www.ncbi.nlm.nih.gov/pubmed/34445414 http://dx.doi.org/10.3390/ijms22168714 |
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author | Choi, Kwang-Eun Kim, Jeong-Min Rhee, JeeEun Park, Ae Kyung Kim, Eun-Jin Kang, Nam Sook |
author_facet | Choi, Kwang-Eun Kim, Jeong-Min Rhee, JeeEun Park, Ae Kyung Kim, Eun-Jin Kang, Nam Sook |
author_sort | Choi, Kwang-Eun |
collection | PubMed |
description | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the COVID-19 pandemic in the world. The spike protein of the various proteins encoded in SARS-CoV-2 binds to human ACE2, fuses, and enters human cells in the respiratory system. Spike protein, however, is highly variable, and many variants were identified continuously. In this study, Korean mutants for spike protein (D614G and D614A-C terminal domain, L455F and F456L-RBD, and Q787H-S2 domain) were investigated in patients. Because RBD in spike protein is related to direct interaction with ACE2, almost all researches were focused on the RBD region or ACE2-free whole domain region. The 3D structure for spike protein complexed with ACE2 was recently released. The stability analysis through RBD distance among each spike protein chain and the binding free energy calculation between spike protein and ACE2 were performed using MD simulation depending on mutant types in 1-, 2-, and 3-open-complex forms. D614G mutant of CT2 domain, showing to be the most prevalent in the global pandemic, showed higher stability in all open-complex forms than the wild type and other mutants. We hope this study will provide an insight into the importance of conformational fluctuation in the whole domain, although RBD is involved in the direct interaction with ACE2. |
format | Online Article Text |
id | pubmed-8395978 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83959782021-08-28 Molecular Dynamics Studies on the Structural Characteristics for the Stability Prediction of SARS-CoV-2 Choi, Kwang-Eun Kim, Jeong-Min Rhee, JeeEun Park, Ae Kyung Kim, Eun-Jin Kang, Nam Sook Int J Mol Sci Article Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the COVID-19 pandemic in the world. The spike protein of the various proteins encoded in SARS-CoV-2 binds to human ACE2, fuses, and enters human cells in the respiratory system. Spike protein, however, is highly variable, and many variants were identified continuously. In this study, Korean mutants for spike protein (D614G and D614A-C terminal domain, L455F and F456L-RBD, and Q787H-S2 domain) were investigated in patients. Because RBD in spike protein is related to direct interaction with ACE2, almost all researches were focused on the RBD region or ACE2-free whole domain region. The 3D structure for spike protein complexed with ACE2 was recently released. The stability analysis through RBD distance among each spike protein chain and the binding free energy calculation between spike protein and ACE2 were performed using MD simulation depending on mutant types in 1-, 2-, and 3-open-complex forms. D614G mutant of CT2 domain, showing to be the most prevalent in the global pandemic, showed higher stability in all open-complex forms than the wild type and other mutants. We hope this study will provide an insight into the importance of conformational fluctuation in the whole domain, although RBD is involved in the direct interaction with ACE2. MDPI 2021-08-13 /pmc/articles/PMC8395978/ /pubmed/34445414 http://dx.doi.org/10.3390/ijms22168714 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Choi, Kwang-Eun Kim, Jeong-Min Rhee, JeeEun Park, Ae Kyung Kim, Eun-Jin Kang, Nam Sook Molecular Dynamics Studies on the Structural Characteristics for the Stability Prediction of SARS-CoV-2 |
title | Molecular Dynamics Studies on the Structural Characteristics for the Stability Prediction of SARS-CoV-2 |
title_full | Molecular Dynamics Studies on the Structural Characteristics for the Stability Prediction of SARS-CoV-2 |
title_fullStr | Molecular Dynamics Studies on the Structural Characteristics for the Stability Prediction of SARS-CoV-2 |
title_full_unstemmed | Molecular Dynamics Studies on the Structural Characteristics for the Stability Prediction of SARS-CoV-2 |
title_short | Molecular Dynamics Studies on the Structural Characteristics for the Stability Prediction of SARS-CoV-2 |
title_sort | molecular dynamics studies on the structural characteristics for the stability prediction of sars-cov-2 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395978/ https://www.ncbi.nlm.nih.gov/pubmed/34445414 http://dx.doi.org/10.3390/ijms22168714 |
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