{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T20:48:49Z","timestamp":1778878129442,"version":"3.51.4"},"reference-count":71,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2019,5,6]],"date-time":"2019-05-06T00:00:00Z","timestamp":1557100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Comput Chem"],"published-print":{"date-parts":[[2019,8,15]]},"abstract":"<jats:p>Type 2 diabetes mellitus (T2Dm) is a neurodegenerative disease, which occurs due to the self\u2010association of human islet amyloid polypeptide (hIAPP), also known as human amylin. It was reported experimentally that choline\u2010<jats:italic>O<\/jats:italic>\u2010sulfate (COS), a small organic molecule having a tertiary amino group and sulfate group, can prevent the aggregation of human amylin without providing the mechanism of the action of COS in the inhibition process. In this work, we investigate the influence of COS on the full\u2010length hIAPP peptide by performing 500\u2009ns classical molecular dynamics simulations. From pure water simulation (without COS), we have identified the residues 11\u201320 and 23\u201336 that mainly participate in the fibril formation, but in the presence of 1.07\u2009M COS these residues become totally free of <jats:italic>\u03b2<\/jats:italic>\u2010sheet conformation. Our results also show that the sulfate oxygen of COS directly interacts with the peptide backbone, which leads to the local disruption of peptide\u2013peptide interaction. Moreover, the presence of favorable peptide\u2010COS vdW interaction energy and high coordination number of COS molecules in the first solvation shell of the peptide indicates the hydrophobic solvation of the peptide residues by COS molecules, which also play a crucial role in the prevention of <jats:italic>\u03b2<\/jats:italic>\u2010sheet formation. Finally, from the potential of mean force (PMFs) calculations, we observe that the free energy between two peptides is more negative in the absence of COS and with increasing concentration of COS, it becomes unfavorable significantly indicating that the peptide dimer formation is most stable in pure water, which becomes less favorable in the presence of COS. \u00a9 2019 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jcc.25851","type":"journal-article","created":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T04:11:12Z","timestamp":1557202272000},"page":"1957-1968","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Molecular dynamics simulation study on the inhibitory effects of choline\u2010<i>O<\/i>\u2010sulfate on hIAPP protofibrilation"],"prefix":"10.1002","volume":"40","author":[{"given":"Srijita","family":"Paul","sequence":"first","affiliation":[{"name":"Department of Chemistry Indian Institute of 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