Abstract

Many serious medical conditions are caused by the accumulation of amyloid aggregates in tissues and organs. One of the most well-known amyloidogenic proteins is the prion protein (PrP), which may undergo conformational change between the normal cellular isoform PrPC and the aggregation-prone isoform PrPSc. Elucidation of this conformational transition is necessary for understanding the onset and propagation of prion diseases. However, the flexibility of PrP hinders its research by the experimental methods of protein structure determination. Here, we implement de novo protein modelling and molecular dynamics simulations to predict the interdomain interactions of the full-length PrPC. Our theoretical findings can serve as the basis for mutational analysis and for further studies of the amyloidogenic behavior of the prion protein.

中文翻译：

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全长Pri蛋白的分子动力学模拟

摘要

淀粉样蛋白聚集体在组织和器官中的积累引起许多严重的医学疾病。最著名的淀粉样蛋白之一是the病毒蛋白（PrP），它可能会在正常细胞亚型PrPC和易于聚集的亚型PrPSc之间发生构象变化。阐明这种构象转变对于理解of病毒疾病的发作和传播是必要的。然而，PrP的灵活性阻碍了其通过蛋白质结构测定实验方法的研究。在这里，我们实施从头蛋白质建模和分子动力学模拟，以预测全长PrPC的域间相互作用。我们的理论发现可以作为突变分析和进一步研究the病毒蛋白的淀粉样蛋白生成行为的基础。