{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:56:53Z","timestamp":1788328613359,"version":"build-2803163510"},"reference-count":83,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T00:00:00Z","timestamp":1710720000000},"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":["Proteins"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Human islet amyloid polypeptide (amylin or hIAPP) is a 37 residue hormone co\u2010secreted with insulin from \u03b2 cells of the pancreas. In patients suffering from type\u20102 diabetes, amylin self\u2010assembles into amyloid fibrils, ultimately leading to the death of the pancreatic cells. However, a research gap exists in preventing and treating such amyloidosis. Plumbagin, a natural compound, has previously been demonstrated to have inhibitory potential against insulin amyloidosis. Our investigation unveils collapsible regions within hIAPP that, upon collapse, facilitates hydrophobic and pi\u2010pi interactions, ultimately leading to aggregation. Intriguingly plumbagin exhibits the ability to bind these specific collapsible regions, thereby impeding the aforementioned interactions that would otherwise drive hIAPP aggregation. We have used atomistic molecular dynamics approach to determine secondary structural changes. MSM shows metastable states forming native like hIAPP structure in presence of PGN. Our in silico results concur with in vitro results. The ThT assay revealed a striking 50% decrease in fluorescence intensity at a 1:1 ratio of hIAPP to Plumbagin. This finding suggests a significant inhibition of amyloid fibril formation by plumbagin, as ThT fluorescence directly correlates with the presence of these fibrils. Further TEM images revealed disappearance of hIAPP fibrils in plumbagin pre\u2010treated hIAPP samples. Also, we have shown that plumbagin disrupts the intermolecular hydrogen bonding in hIAPP fibrils leading to an increase in the average beta strand spacing, thereby causing disaggregation of pre\u2010formed fibrils demonstrating overall disruption of the aggregation machinery of hIAPP. Our work is the first to report a detailed atomistic simulation of 22\u2009\u03bcs for hIAPP. Overall, our studies put plumbagin as a potential candidate for both preventive and therapeutic candidate for hIAPP amyloidosis.<\/jats:p>","DOI":"10.1002\/prot.26682","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T05:59:03Z","timestamp":1710741543000},"page":"1070-1084","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Natural compound plumbagin based inhibition of\n                    <scp>hIAPP<\/scp>\n                    revealed by Markov state models based on\n                    <scp>MD<\/scp>\n                    data along with experimental validations"],"prefix":"10.1002","volume":"92","author":[{"given":"Faisal","family":"Nabi","sequence":"first","affiliation":[{"name":"Interdisciplinary Biotechnology Unit, Aligarh Muslim University  Aligarh 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