Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Wisconsin, USA.
Biophys J. 2010 Feb 3;98(3):443-51. doi: 10.1016/j.bpj.2009.10.029.
Amyloid deposits of amylin in the pancreas are an important characteristic feature found in patients with Type-2 diabetes. The aggregate has been considered important in the disease pathology and has been studied extensively. However, the secondary structures of the individual peptide have not been clearly identified. In this work, we present detailed solution structures of rat amylin using a combination of Monte Carlo and molecular dynamics simulations. A new Monte Carlo method is presented to determine the free energy of distinct biomolecular conformations. Both folded and random-coil conformations of rat amylin are observed in water and their relative stability is examined in detail. The former contains an alpha-helical segment comprised of residues 7-17. We find that at room temperature the folded structure is more stable, whereas at higher temperatures the random-coil structure predominates. From the configurations and weights we calculate the alpha-carbon NMR chemical shifts, with results that are in reasonable agreement with experiments of others. We also calculate the infrared spectrum in the amide I stretch regime, and the results are in fair agreement with the experimental line shape presented herein.
胰岛细胞中胰岛淀粉样多肽的沉淀是 2 型糖尿病患者的一个重要特征。该聚集体在疾病病理中被认为很重要，并且已经被广泛研究。然而，单个肽的二级结构尚未被明确确定。在这项工作中，我们使用蒙特卡罗和分子动力学模拟的组合，提出了详细的大鼠胰岛淀粉样多肽的溶液结构。提出了一种新的蒙特卡罗方法来确定不同生物分子构象的自由能。在水中观察到大鼠胰岛淀粉样多肽的折叠和无规卷曲构象，并且详细检查了它们的相对稳定性。前者包含由残基 7-17 组成的α-螺旋片段。我们发现，在室温下，折叠结构更稳定，而在较高温度下，无规卷曲结构占主导地位。从构象和权重我们计算了α-碳原子 NMR 化学位移，结果与其他人的实验结果相当吻合。我们还计算了酰胺 I 伸缩谱区的红外光谱，结果与本文提出的实验谱线形状相当吻合。
