Coarse-grained models for protein aggregation.
Coarse-grained models for protein aggregation.
复制标题
DOI：
10.1016/j.sbi.2011.02.002
复制
发表时间：
2011-04
影响因子：
6.8
通讯作者：
Chun Wu;J. Shea
中科院分区：
文献类型：
--
作者：
Chun Wu;J. Shea
可溶性蛋白质聚集成纤维状物质是一个复杂的过程，跨越许多长度和时间尺度，并且涉及大量路径内和路径外中间物质的形成。尽管存在这种复杂性，但聚合过程背后的几个要素似乎是通用的。动力学通常遵循成核生长过程，具有非常不同序列的蛋白质聚集形成相似的原纤维结构，填充具有足够结构相似性的中间体以结合常见抗体。本综述重点关注一种计算方法，该方法利用聚合的共同特征来简化或“粗粒度”蛋白质的表示。我们重点介绍了粗粒度建模的最新进展，并说明了这些模型如何能够为蛋白质聚集机制和聚集中间体的性质提供新的线索。讨论了单体状态下易于聚集的构象的作用以及固有的β-折叠和聚集倾向在调节聚集途径中的影响。
The aggregation of soluble proteins into fibrillar species is a complex process that spans many lengths and time scales, and that involves the formation of numerous on-pathway and off-pathway intermediate species. Despite this complexity, several elements underlying the aggregation process appear to be universal. The kinetics typically follows a nucleation-growth process, and proteins with very different sequences aggregate to form similar fibril structures, populating intermediates with sufficient structural similarity to bind to a common antibody. This review focuses on a computational approach that exploits the common features of aggregation to simplify or ‘coarse-grain’ the representation of the protein. We highlight recent developments in coarse-grained modeling and illustrate how these models have been able to shed new light into the mechanisms of protein aggregation and the nature of aggregation intermediates. The roles of aggregation prone conformations in the monomeric state and the influence of inherent β-sheet and aggregation propensities in modulating aggregation pathways are discussed.