{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T17:27:16Z","timestamp":1779902836016,"version":"3.53.1"},"reference-count":43,"publisher":"Proceedings of the National Academy of Sciences","issue":"50","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,12,14]]},"abstract":"<jats:p>Experimental findings suggest that oligomeric forms of the amyloid \u03b2 protein (A\u03b2) play a critical role in Alzheimer's disease. Thus, elucidating their structure and the mechanisms of their formation is critical for developing therapeutic agents. We use discrete molecular dynamics simulations and a four-bead protein model to study oligomerization of two predominant alloforms, A\u03b240 and A\u03b242, at the atomic level. The four-bead model incorporates backbone hydrogen-bond interactions and amino acid-specific interactions mediated through hydrophobic and hydrophilic elements of the side chains. During the simulations we observe monomer folding and aggregation of monomers into oligomers of variable sizes. A\u03b240 forms significantly more dimers than A\u03b242, whereas pentamers are significantly more abundant in A\u03b242 relative to A\u03b240. Structure analysis reveals a turn centered at Gly-37\u2013Gly-38 that is present in a folded A\u03b242 monomer but not in a folded A\u03b240 monomer and is associated with the first contacts that form during monomer folding. Our results suggest that this turn plays an important role in A\u03b242 pentamer formation. A\u03b2 pentamers have a globular structure comprising hydrophobic residues within the pentamer's core and hydrophilic N-terminal residues at the surface of the pentamer. The N termini of A\u03b240 pentamers are more spatially restricted than A\u03b242 pentamers. A\u03b240 pentamers form a \u03b2-strand structure involving Ala-2\u2013Phe-4, which is absent in A\u03b242 pentamers. These structural differences imply a different degree of hydrophobic core exposure between pentamers of the two alloforms, with the hydrophobic core of the A\u03b242 pentamer being more exposed and thus more prone to form larger oligomers.<\/jats:p>","DOI":"10.1073\/pnas.0408153101","type":"journal-article","created":{"date-parts":[[2004,12,7]],"date-time":"2004-12-07T01:24:54Z","timestamp":1102382694000},"page":"17345-17350","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":310,"title":["<i>In silico<\/i>\n            study of amyloid \u03b2-protein folding and oligomerization"],"prefix":"10.1073","volume":"101","author":[{"given":"B.","family":"Urbanc","sequence":"first","affiliation":[{"name":"Center for Polymer Studies, Department of Physics, Boston University, Boston, MA 02215; and Center for Neurologic Diseases, Brigham and Women's Hospital, and Department of Neurology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Cruz","sequence":"additional","affiliation":[{"name":"Center for Polymer Studies, Department of Physics, Boston University, Boston, MA 02215; and Center for Neurologic Diseases, Brigham and Women's Hospital, and Department of Neurology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Yun","sequence":"additional","affiliation":[{"name":"Center for Polymer Studies, Department of Physics, Boston University, Boston, MA 02215; and Center for Neurologic Diseases, Brigham and Women's Hospital, and Department of Neurology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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