Simulations of pH and thermal effects on SARS-CoV-2 spike glycoprotein
We performed triplicate and long-time all-atom molecular dynamics simulations to investigate the structures and dynamics of the SARS-CoV-2 spike glycoprotein (S-protein) for a broad range of pH = 1 through 11 and temperatures of 3°C through 75°C. This study elucidates the complex interplay between p...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-02-01
|
| Series: | Frontiers in Molecular Biosciences |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2025.1545041/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823859417661046784 |
|---|---|
| author | Ziyuan Niu Georgios Kementzidis Miriam Rafailovich Marcia Simon Evangelos Papadopoulos Bertal H. Aktas Yuefan Deng |
| author_facet | Ziyuan Niu Georgios Kementzidis Miriam Rafailovich Marcia Simon Evangelos Papadopoulos Bertal H. Aktas Yuefan Deng |
| author_sort | Ziyuan Niu |
| collection | DOAJ |
| description | We performed triplicate and long-time all-atom molecular dynamics simulations to investigate the structures and dynamics of the SARS-CoV-2 spike glycoprotein (S-protein) for a broad range of pH = 1 through 11 and temperatures of 3°C through 75°C. This study elucidates the complex interplay between pH and thermal effects on S-protein structures, with implications for its behavior under diverse conditions, and identifies the RBD as a primary region of the structural deviations. We found: 1) Structural deviations in the S-protein backbone at pH = 1 are 210% greater than those at pH = 7 at 75°C, with most of the deviations appearing in the receptor-binding domain (RBD). Smaller structural changes are observed at pH = 3 and 11. 2) The pH and thermal conditions impact on the protein structures: substantial acidic and basic conditions expand the protein’s solvent exposure, while high heat contracts. This effect is primarily pH-driven at extreme acidity and thermo-driven at moderate pH. 3) The Gibbs free energy landscape reveals that pH as the main driver of structural changes. 4) The parametrized methods enable the predictions of the S-protein properties at any reasonable pH and thermal conditions without explicit MD simulations. |
| format | Article |
| id | doaj-art-a578af265f0b4d959c01f94e5d04276a |
| institution | Kabale University |
| issn | 2296-889X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj-art-a578af265f0b4d959c01f94e5d04276a2025-02-11T05:10:19ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2025-02-011210.3389/fmolb.2025.15450411545041Simulations of pH and thermal effects on SARS-CoV-2 spike glycoproteinZiyuan Niu0Georgios Kementzidis1Miriam Rafailovich2Marcia Simon3Evangelos Papadopoulos4Bertal H. Aktas5Yuefan Deng6Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, United StatesDepartment of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, United StatesDepartment of Materials Science and Chemical Engineering, Stony Brook University, Stony Brook, NY, United StatesDepartment of Oral Biology and Pathology, Stony Brook University, Stony Brook, NY, United StatesDivision of Hematology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United StatesDivision of Hematology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United StatesDepartment of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, United StatesWe performed triplicate and long-time all-atom molecular dynamics simulations to investigate the structures and dynamics of the SARS-CoV-2 spike glycoprotein (S-protein) for a broad range of pH = 1 through 11 and temperatures of 3°C through 75°C. This study elucidates the complex interplay between pH and thermal effects on S-protein structures, with implications for its behavior under diverse conditions, and identifies the RBD as a primary region of the structural deviations. We found: 1) Structural deviations in the S-protein backbone at pH = 1 are 210% greater than those at pH = 7 at 75°C, with most of the deviations appearing in the receptor-binding domain (RBD). Smaller structural changes are observed at pH = 3 and 11. 2) The pH and thermal conditions impact on the protein structures: substantial acidic and basic conditions expand the protein’s solvent exposure, while high heat contracts. This effect is primarily pH-driven at extreme acidity and thermo-driven at moderate pH. 3) The Gibbs free energy landscape reveals that pH as the main driver of structural changes. 4) The parametrized methods enable the predictions of the S-protein properties at any reasonable pH and thermal conditions without explicit MD simulations.https://www.frontiersin.org/articles/10.3389/fmolb.2025.1545041/fullSARS-CoV-2spike proteinAAMDpH solventthermal conditions |
| spellingShingle | Ziyuan Niu Georgios Kementzidis Miriam Rafailovich Marcia Simon Evangelos Papadopoulos Bertal H. Aktas Yuefan Deng Simulations of pH and thermal effects on SARS-CoV-2 spike glycoprotein Frontiers in Molecular Biosciences SARS-CoV-2 spike protein AAMD pH solvent thermal conditions |
| title | Simulations of pH and thermal effects on SARS-CoV-2 spike glycoprotein |
| title_full | Simulations of pH and thermal effects on SARS-CoV-2 spike glycoprotein |
| title_fullStr | Simulations of pH and thermal effects on SARS-CoV-2 spike glycoprotein |
| title_full_unstemmed | Simulations of pH and thermal effects on SARS-CoV-2 spike glycoprotein |
| title_short | Simulations of pH and thermal effects on SARS-CoV-2 spike glycoprotein |
| title_sort | simulations of ph and thermal effects on sars cov 2 spike glycoprotein |
| topic | SARS-CoV-2 spike protein AAMD pH solvent thermal conditions |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2025.1545041/full |
| work_keys_str_mv | AT ziyuanniu simulationsofphandthermaleffectsonsarscov2spikeglycoprotein AT georgioskementzidis simulationsofphandthermaleffectsonsarscov2spikeglycoprotein AT miriamrafailovich simulationsofphandthermaleffectsonsarscov2spikeglycoprotein AT marciasimon simulationsofphandthermaleffectsonsarscov2spikeglycoprotein AT evangelospapadopoulos simulationsofphandthermaleffectsonsarscov2spikeglycoprotein AT bertalhaktas simulationsofphandthermaleffectsonsarscov2spikeglycoprotein AT yuefandeng simulationsofphandthermaleffectsonsarscov2spikeglycoprotein |