Department of Chemistry, Aligarh Muslim University, Aligarh, 202002, UP, India.
J Mol Model. 2022 Jun 14;28(7):188. doi: 10.1007/s00894-022-05180-1.
The human islet amyloid polypeptide or amylin is secreted along with insulin by pancreatic islets. Under the drastic environmental conditions, amylin can aggregate to form amyloid fibrils. This amyloid plaque of hIAPP in the pancreatic cells is the cause of type II diabetes. Early stages of amylin aggregates are more cytotoxic than the matured fibrils. Here, we have used the all-atom molecular dynamic simulation to see the effect of water, TMAO, urea and urea/TMAO having ratio 2:1 of different concentrations on the amylin protein. Our study suggest that the amylin protein forms β-sheets in its monomeric form and may cause the aggregation of protein through the residue 13-17 and the C-terminal region. α-Helical content of protein increases with an increase in TMAO concentration by decreasing the SASA value of protein, increase in intramolecular hydrogen bonds and on making the short-range hydrophobic interactions. Electrostatic potential surfaces show that hydrophobic groups are buried and normalised configurational entropy of backbone, and side-chain atoms is lesser in the presence of TMAO, whereas opposite behaviour is obtained in the case of urea. Counteraction effect of TMAO using Kast model towards urea is also observed in ternary solution of urea/TMAO.
人胰岛淀粉样多肽或胰岛淀粉样多肽与胰岛素一起由胰岛分泌。在剧烈的环境条件下，胰岛淀粉样多肽可以聚集形成淀粉样纤维。这种胰岛细胞中的 hIAPP 淀粉样斑块是 II 型糖尿病的病因。胰岛淀粉样多肽的早期聚集比成熟纤维更具细胞毒性。在这里，我们使用全原子分子动力学模拟来观察水、TMAO、尿素和 2:1 比例不同浓度的尿素/TMAO 对胰岛淀粉样多肽蛋白的影响。我们的研究表明，胰岛淀粉样多肽蛋白在其单体形式下形成 β-折叠，并可能通过残基 13-17 和 C 末端区域引起蛋白质的聚集。随着 TMAO 浓度的增加，蛋白质的α-螺旋含量增加，通过降低蛋白质的 SASA 值、增加分子内氢键以及形成短程疏水相互作用来实现。静电势能表面表明，在 TMAO 存在下，疏水区被埋藏，并且主链原子的构象熵正常化，而在尿素的情况下则得到相反的结果。在用 Kast 模型对尿素的反作用效应也在尿素/TMAO 的三元溶液中观察到。
