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However, the underlying molecular mechanism is not well understood. In this study, as a first step to understand pH\u2010modulated A\u03b2 fibril formation, we investigated the conformations of A\u03b2 (16\u201322) octamers by performing extensive all\u2010atom replica exchange molecular dynamics simulations at both neutral and acidic pH. Our simulations showed that the residues Phe20 and Ala21 in the C terminal have higher \u03b2\u2010sheet probability (78.8%, 55.8%) at acidic pH than (62.3%, 43.6%) at neutral pH. Out\u2010of\u2010register antiparallel \u03b2\u2010strand alignments of the A\u03b2 (16\u201322) peptide are predominantly in the 1\u2010, 2\u2010, and 3\u2010residue shifts at both pH conditions, which agrees well with solid\u2010state NMR results on A\u03b2 peptides. We also found that there are multiple in\u2010register and out\u2010of\u2010register parallel \u03b2\u2010strand alignments under both pH conditions. However, the pH conditions affect the probability of \u03b2\u2010strand alignments for the A\u03b2 (16\u201322) peptide, and the residue\u2010residue interaction of bilayer \u03b2\u2010sheet and \u03b2\u2010barrel are different at different pH conditions. Our analysis showed that the electrostatic interactions among peptides are much stronger at neutral pH than at acidic pH, while the vdW interactions are slightly stronger at acidic pH than at neutral pH. These results provide atomistic insight into the early stage of aggregation of amyloid\u2010\u03b2 (A\u03b2) peptides at acidic and neutral pH conditions.<\/jats:p>","DOI":"10.1002\/prot.70012","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T01:29:54Z","timestamp":1751419794000},"page":"2101-2111","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>pH<\/scp>\n                    \u2010Dependent \u03b2\u2010Strand Alignment of the Alzheimer's Amyloid\u2010\u03b2 (16\u201322) Peptide"],"prefix":"10.1002","volume":"93","author":[{"given":"Junfeng","family":"Wan","sequence":"first","affiliation":[{"name":"Department of Mathematics and Physics Shanghai University of Electric Power  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yin","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Physics, Key Laboratory of Computational Physical Sciences (Ministry of Education) Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9110-5585","authenticated-orcid":false,"given":"Philippe","family":"Derreumaux","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie Th\u00e9orique, UPR 9080 CNRS Universit\u00e9 Paris Cit\u00e9, Institut de Biologie Physico Chimique, et Institut Universitaire de France  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5814-3328","authenticated-orcid":false,"given":"Guanghong","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Physics, Key Laboratory of Computational Physical Sciences (Ministry of Education) Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Mathematics and Physics Shanghai University of Electric Power  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"World Alzheimer Report 2015. 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