{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T13:07:17Z","timestamp":1763125637502,"version":"3.45.0"},"reference-count":62,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The process of islet amyloid formation by the polypeptide hormone human IAPP contributes to the loss of\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010cell function in type\u20102 diabetes. The S20G mutation in human IAPP has been linked to an increased risk of diabetes in individuals of Japanese and Chinese ancestry and leads to more rapid amyloid formation in vitro. The molecular basis of the S20G enhancement of amyloid formation was explored via experiments with genetically coded and non\u2010coded amino acids combined with energy decomposition analysis. Ser20 was replaced by L\u2010Ala, Gly, D\u2010Ser, and D\u2010Ala. All variants form amyloid more rapidly than wild type IAPP, and the largest effect is observed with the S20G mutant. The rank order of the rates to form amyloid is S20G \u2265 S20D\u2010Ala &gt; S20A &gt; S20D\u2010Ser &gt; wild type. Energy decomposition calculations were used to examine the steric consequences of replacing Ser\u201020 with Gly and with D and L\u2010amino acids in existing models of IAPP amyloid fibrils. The experimental data and computational analysis indicate that the accelerated rate of amyloid formation by S20G IAPP is due to a combination of factors and cannot be ascribed to just the removal of unfavorable sidechain steric interactions in the fibril state or solely due to the need to populate conformations with a positive value of backbone dihedral angle \u03d5. Constraining the backbone conformation propensities to favor positive \u03d5 angles appears to have the dominant effect.\n                  <\/jats:p>","DOI":"10.1002\/pro.70308","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T07:21:57Z","timestamp":1761808917000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Experimental and computational analysis of the basis for accelerated amyloid formation by a disease linked mutant of human islet amyloid polypeptide"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9809-4193","authenticated-orcid":false,"given":"Lakshan","family":"Manathunga","sequence":"first","affiliation":[{"name":"Department of Chemistry Stony Brook University  Stony Brook New York USA"},{"name":"Laufer Center for Physical and Quantitative Biology Stony Brook University  Stony Brook New York 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