Exploring the Paths of (Virus) Assembly
Exploring the Paths of (Virus) Assembly
复制标题
DOI：
10.1016/j.bpj.2010.06.030
复制
发表时间：
2010-09-08
影响因子：
3.4
通讯作者：
Zlotnick, Adam
中科院分区：
文献类型：
--
作者：
Moisant, Paul;Neeman, Henry;Zlotnick, Adam
具有数百个亚单位的病毒的组装或具有数百个氨基酸的蛋白质的折叠复杂的生物反应通常是自发和快速的。在这里，我们研究了一套完整的中间体，可用于组装一个假设的病毒样颗粒和这些中间体之间的连通性在图论启发的研究。使用建立程序，假设理想的几何形状，我们列举了完整的一套2，423，313种，用于从30个二聚体亚基形成二十面体。每个n-亚基中间体的稳定性由亚基之间的接触数定义。形成一个中间体的概率是基于从它的前辈到它的路径的数量。在定义对组装影响最大的群体子集时，基于稳定性和概率的标准都会选择一小群紧凑和退化的物种;因此，只有几百个中间体对组装做出了可测量的贡献。尽管可能的中间体的数量随着衣壳中亚基的数量而组合地增长，但对反应做出重大贡献的中间体的数量以小得多的函数增长，这一结果可能有助于我们理解组装和折叠反应。
Assembly of viruses that have hundreds of subunits or folding of proteins that have hundreds of amino acids complex biological reactions-are often spontaneous and rapid. Here, we examine the complete set of intermediates available for the assembly of a hypothetical viruslike particle and the connectivity between these intermediates in a graph-theory-inspired study. Using a build-up procedure, assuming ideal geometry, we enumerated the complete set of 2,423,313 species for formation of an icosahedron from 30 dimeric subunits. Stability of each n-subunit intermediate was defined by the number of contacts between subunits. The probability of forming an intermediate was based on the number of paths to it from its precedecessors. When defining population subsets predicted to have the greatest impact on assembly, both stability- and probability-based criteria select a small group of compact and degenerate species; ergo, only a few hundred intermediates make a measurable contribution to assembly. Though the number of possible intermediates grows combinatorially with the number of subunits in the capsid, the number of intermediates that make a significant contribution to the reaction grows by a much smaller function, a result that may contribute to our understanding of assembly and folding reactions.