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...
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| Format: | Article |
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/16/8714 |
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| author | Kwang-Eun Choi Jeong-Min Kim JeeEun Rhee Ae Kyung Park Eun-Jin Kim Nam Sook Kang |
| author_facet | Kwang-Eun Choi Jeong-Min Kim JeeEun Rhee Ae Kyung Park Eun-Jin Kim Nam Sook Kang |
| author_sort | Kwang-Eun Choi |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T08:44:40Z |
| format | Article |
| id | doaj.art-4162d87b2b614172a64b280ce5b69519 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:44:40Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4162d87b2b614172a64b280ce5b695192023-11-22T07:59:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216871410.3390/ijms22168714Molecular Dynamics Studies on the Structural Characteristics for the Stability Prediction of SARS-CoV-2Kwang-Eun Choi0Jeong-Min Kim1JeeEun Rhee2Ae Kyung Park3Eun-Jin Kim4Nam Sook Kang5Graduate School of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, KoreaDivision of Emerging Infectious Diseases, Bureau of Infectious Disease Diagnosis Control, Korea Disease Control and Prevention Agency, 187 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si 28159, KoreaDivision of Emerging Infectious Diseases, Bureau of Infectious Disease Diagnosis Control, Korea Disease Control and Prevention Agency, 187 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si 28159, KoreaDivision of Emerging Infectious Diseases, Bureau of Infectious Disease Diagnosis Control, Korea Disease Control and Prevention Agency, 187 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si 28159, KoreaDivision of Emerging Infectious Diseases, Bureau of Infectious Disease Diagnosis Control, Korea Disease Control and Prevention Agency, 187 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si 28159, KoreaGraduate School of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, KoreaSevere 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.https://www.mdpi.com/1422-0067/22/16/8714SARS-CoV-2spike proteinmutantMD simulation |
| spellingShingle | Kwang-Eun Choi Jeong-Min Kim JeeEun Rhee Ae Kyung Park Eun-Jin Kim Nam Sook Kang Molecular Dynamics Studies on the Structural Characteristics for the Stability Prediction of SARS-CoV-2 International Journal of Molecular Sciences SARS-CoV-2 spike protein mutant MD simulation |
| 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 | SARS-CoV-2 spike protein mutant MD simulation |
| url | https://www.mdpi.com/1422-0067/22/16/8714 |
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