{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:06:19Z","timestamp":1789985179577,"version":"4.0.1"},"reference-count":54,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004329","name":"Slovenian Research and Innovation Agency","doi-asserted-by":"publisher","award":["P2-0412"],"award-info":[{"award-number":["P2-0412"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]},{"award":["P2-0412"],"award-info":[{"award-number":["P2-0412"]}],"id":[{"id":"https:\/\/ror.org\/059bp8k51","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Protein folding is highly sensitive to environmental conditions such as pH, which can influence internal hydrogen bonding and interactions with the solvent. In this study, we use our FitFoldData online tool to analyze published differential scanning calorimetry (DSC) data on the unfolding of four proteins measured across different pH values. For each dataset, we examine the fitted thermodynamic parameters, including the intrapeptide and peptide\u2013solvent hydrogen-bonding energies (h and hps) and the Zimm\u2013Bragg cooperativity parameter (\u03c3). In the analyzed datasets, under both acidic and alkaline conditions, h and hps range from 2 to 8.5 kJ\/mol, while \u03c3 is on the order of 10\u22123 to 10\u22122. In addition, the two-state cooperativity parameter k2 is estimated from the DSC curves as the enthalpy ratio. By considering the size-dependent relative fluctuation, 1\/N, we introduce a \u201ctwo-state range\u201d around the value k2=1 for each protein with a given number N of peptide units. We find that pH can shift proteins into or out of the two-state range of k2 values.<\/jats:p>","DOI":"10.3390\/biom16091368","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:01:38Z","timestamp":1789981298000},"page":"1368","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["pH-Dependent Stability and Cooperativity of Protein Unfolding from Differential Scanning Calorimetry Using FitFoldData"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4815-7279","authenticated-orcid":false,"given":"Knarik","family":"Yeritsyan","sequence":"first","affiliation":[{"name":"Laboratory of Organic Matter Physics, University of Nova Gorica, Vipavska 13, SI-5000 Nova Gorica, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4037-5857","authenticated-orcid":false,"given":"Vladimir","family":"Uversky","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, USF Health Byrd Alzheimer\u2019s Research Institute, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., MDC07, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0563-5403","authenticated-orcid":false,"given":"Artem","family":"Badasyan","sequence":"additional","affiliation":[{"name":"Materials Research Laboratory, University of Nova Gorica, Vipavska 13, SI-5000 Nova Gorica, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0065-3233(08)60608-7","article-title":"Some Factors in the Interpretation of Protein Denaturation","volume":"Volume 14","author":"Kauzmann","year":"1959","journal-title":"Advances in Protein Chemistry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1002\/bip.360261104","article-title":"Protein stability curves","volume":"26","author":"Becktel","year":"1987","journal-title":"Biopolymers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1021\/cr960383c","article-title":"Protein Structure and the Energetics of Protein Stability","volume":"97","author":"Robertson","year":"1997","journal-title":"Chem. 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