{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:03:58Z","timestamp":1790636638857,"version":"4.1.0"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,24]],"date-time":"2022-03-24T00:00:00Z","timestamp":1648080000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Petchra Pra Jom Klao Doctoral Scholarship, KMUTT"},{"DOI":"10.13039\/501100017170","name":"Thailand Science Research and Innovation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100017170","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Aggregation of unfolded or misfolded proteins into amyloid fibrils can cause various diseases in humans. However, the fibrils synthesized in vitro can be developed toward useful biomaterials under some physicochemical conditions. In this study, atomistic molecular dynamics simulations were performed to address the mechanism of beta-sheet formation of the unfolded hen egg-white lysozyme (HEWL) under a high temperature and low pH. Simulations of the protonated HEWL at pH 2 and the non-protonated HEWL at pH 7 were performed at the highly elevated temperature of 450 K to accelerate the unfolding, followed by the 333 K temperature to emulate some previous\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies. The simulations showed that HEWL unfolded faster, and higher beta-strand contents were observed at pH 2. In addition, one of the simulation replicas at pH 2 showed that the beta-strand forming sequence was consistent with the \u2018K-peptide\u2019, proposed as the core region for amyloidosis in previous experimental studies. Beta-strand formation mechanisms at the earlier stage of amyloidosis were explained in terms of the radial distribution of the amino acids. The separation between groups of positively charged sidechains from the hydrophobic core corresponded to the clustering of the hydrophobic residues and beta-strand formation.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0249742","type":"journal-article","created":{"date-parts":[[2022,3,24]],"date-time":"2022-03-24T17:28:01Z","timestamp":1648142881000},"page":"e0249742","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":21,"title":["Molecular dynamics study on the effects of charged amino acid distribution under low pH condition to the unfolding of hen egg white lysozyme and formation of beta strands"],"prefix":"10.1371","volume":"17","author":[{"given":"Husnul Fuad","family":"Zein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrar","family":"Alam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piyapong","family":"Asanithi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4468-8885","authenticated-orcid":true,"given":"Thana","family":"Sutthibutpong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,3,24]]},"reference":[{"key":"pone.0249742.ref001","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1002\/jrs.5567","article-title":"Amyloid formation kinetics of hen egg white lysozyme under heat and acidic conditions revealed by Raman spectroscopy","volume":"50","author":"L Xing","year":"2019","journal-title":"J Raman Spectrosc"},{"key":"pone.0249742.ref002","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/j.jmb.2006.11.084","article-title":"Lysozyme Amyloidogenesis Is Accelerated by Specific Nicking and Fragmentation but Decelerated by Intact Protein Binding and Conversion","volume":"366","author":"R Mishra","year":"2007","journal-title":"J Mol Biol"},{"key":"pone.0249742.ref003","doi-asserted-by":"crossref","first-page":"14446","DOI":"10.1073\/pnas.1208228109","article-title":"Distinguishing crystal-like amyloid fibrils and glass-like amorphous aggregates from their kinetics of formation","volume":"109","author":"Y Yoshimura","year":"2012","journal-title":"Proc Natl Acad Sci"},{"key":"pone.0249742.ref004","doi-asserted-by":"crossref","first-page":"233","DOI":"10.4161\/19336896.2014.968464","article-title":"When amyloids become prions.","volume":"8","author":"R. 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