{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T18:12:58Z","timestamp":1764785578222,"version":"3.41.2"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>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\u00b0C through 75\u00b0C. 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\u00b0C, 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\u2019s 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.<\/jats:p>","DOI":"10.3389\/fmolb.2025.1545041","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T05:10:53Z","timestamp":1739250653000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Simulations of pH and thermal effects on SARS-CoV-2 spike glycoprotein"],"prefix":"10.3389","volume":"12","author":[{"given":"Ziyuan","family":"Niu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgios","family":"Kementzidis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam","family":"Rafailovich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcia","family":"Simon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evangelos","family":"Papadopoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bertal H.","family":"Aktas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuefan","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"B2","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1126\/science.abj8754","article-title":"Accurate prediction of protein structures and interactions using a three-track neural network","volume":"373","author":"Baek","year":"2021","journal-title":"Science"},{"key":"B3","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1002\/(sici)1097-0134(199702)27:2<213::aid-prot8>3.0.co;2-g","article-title":"Geometric versus topological clustering: an insight into conformation mapping","volume":"27","author":"Becker","year":"1997","journal-title":"Proteins"},{"key":"B4","doi-asserted-by":"publisher","first-page":"3257","DOI":"10.1021\/ct300400x","article-title":"Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone \u03c6, \u03c8 and side-chain \u03c7(1) and \u03c7(2) dihedral angles","volume":"8","author":"Best","year":"2012","journal-title":"J. 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