The formation of dense, linear arrays (fibrils) by biomolecules is the hallmark of a number of degenerative diseases, such as Alzheimer’s and type-2 diabetes. Protein fibrils have also attracted interest as building blocks for new materials. It has long been recognized that surfaces can affect the fibrillation process. Recent work on the model fibril forming protein human islet amyloid polypeptide (hIAPP) has shown that while the protein concentration is highest at hydrophobic surfaces, the rate of fibril formation is lower than on other surfaces. To understand this, replica exchange molecular dynamics simulations were used to investigate the conformations that hIAPP adopts on surfaces of different hydrophobicities. The hydrophobic surface stabilizes $\alpha$-helical structures which are significantly different to those found on the hydrophilic surface and in bulk solution. There is also a greatly reduced conformational ensemble on the hydrophobic surface due to long-lived contacts between hydrophobic residues on the protein and the surface. This new microscopic information will help us determine the mechanism of the enhancement of fibril formation on surfaces and provides new insight into the effect of nanointerfaces and protein conformation.

中文翻译：

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表面化学对胰岛淀粉样多肽构象的影响。

生物分子形成密集的线性阵列（原纤维）是许多退行性疾病的标志，例如阿尔茨海默氏症和 2 型糖尿病。蛋白质原纤维作为新材料的构建块也引起了人们的兴趣。人们早就认识到表面会影响原纤化过程。最近对模型原纤维形成蛋白人胰岛淀粉样多肽 (hIAPP) 的研究表明，虽然疏水表面的蛋白质浓度最高，但原纤维形成率低于其他表面。为了理解这一点，使用复制交换分子动力学模拟来研究 hIAPP 在不同疏水性表面上采用的构象。疏水表面稳定$\alpha$-与亲水表面和本体溶液中发现的那些显着不同的螺旋结构。由于蛋白质和表面上的疏水残基之间的长期接触，疏水表面上的构象集合也大大减少。这一新的微观信息将帮助我们确定增强表面原纤维形成的机制，并为纳米界面和蛋白质构象的影响提供新的见解。