Computer Simulations of Alzheimer's amyloid β-protein folding and assembly
Computer Simulations of Alzheimer's amyloid β-protein folding and assembly
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DOI：
10.2174/156720506779025170
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发表时间：
2006-12-01
影响因子：
2.1
通讯作者：
Stanley, H. Eugene
中科院分区：
文献类型：
--
作者：
Urbanc, Brigita;Cruz, Luis;Stanley, H. Eugene
淀粉样β蛋白(Aβ)的病理性折叠和聚集被广泛认为是从分子水平上理解阿尔茨海默病(AD)的核心。研究Aβ自组装的实验方法是有限的，因为大多数相关的聚集体都是准稳定的和不均匀的。相比之下，模拟可以提供对问题的重要见解，包括分子中对药物靶向有吸引力的特定位置，以及导致有毒组件生产的组装路径的细节。在这里，我们回顾了计算机模拟方法，以了解Aβ的结构生物学。我们讨论了这些模拟帮助指导实验工作的方式，以及实验结果如何指导理论和模拟方法的发展，这些方法可能对理解病理蛋白质折叠和组装有普遍意义。
Pathological folding and aggregation of the amyloid beta-protein (A beta) are widely perceived as central to understanding Alzheimer's disease (AD) at the molecular level. Experimental approaches to study A beta self-assembly are limited, because most relevant aggregates are quasi-stable and inhomogeneous. In contrast, simulations can provide significant insights into the problem, including specific sites in the molecule that would be attractive for drug targeting and details of the assembly pathways leading to the production of toxic assemblies. Here we review computer simulation approaches to understanding the structural biology of A beta. We discuss the ways in which these simulations help guide experimental work, and in turn, how experimental results guide the development of theoretical and simulation approaches that may be of general utility in understanding pathologic protein folding and assembly.