Exploring the parameter space of complex self-assembly through virus capsid models
Exploring the parameter space of complex self-assembly through virus capsid models
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DOI：
10.1529/biophysj.107.107284
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发表时间：
2008-02-01
影响因子：
3.4
通讯作者：
Schwartz, Russell
中科院分区：
文献类型：
--
作者：
Sweeney, Blake;Zhang, Tiequan;Schwartz, Russell
我们使用离散事件随机模拟来表征二十面体病毒衣壳组装模型的参数空间作为单体-单体结合率的函数。模拟揭示了以三种主要组装机制为特征的参数空间、标准成核限制单体吸积途径和两种不同的分层组装途径，以及以动力学捕获物质为特征的非生产性区域。大部分生产参数空间还由这些域之间的边界区域组成，其中混合路径可能起作用。研究比较的更简单的八聚体系统揭示了三个类似的途径，但其特征是与二十面体模型中可见的急剧变化相比，对参数变化的敏感性要低得多。该模型表明，组装条件的适度变化（与体外和体内组装环境之间的预期差异一致）可能会导致组装途径发生重大变化。这些结果表明，我们在从理论或体外模型得出有关体内衣壳自组装动力学的结论时必须谨慎，因为系统可访问的基本组装机制的性质在简单和复杂模型系统之间、理论模型和模拟结果之间以及体外和体内组装条件之间可能存在很大差异。
We use discrete event stochastic simulations to characterize the parameter space of a model of icosahedral viral capsid assembly as functions of monomer-monomer binding rates. The simulations reveal a parameter space characterized by three major assembly mechanisms, a standard nucleation-limited monomer-accretion pathway and two distinct hierarchical assembly pathways, as well as unproductive regions characterized by kinetically trapped species. Much of the productive parameter space also consists of border regions between these domains where hybrid pathways are likely to operate. A simpler octamer system studied for comparison reveals three analogous pathways, but is characterized by much lesser sensitivity to parameter variations in contrast to the sharp changes visible in the icosahedral model. The model suggests that modest changes in assembly conditions, consistent with expected differences between in vitro and in vivo assembly environments, could produce substantial shifts in assembly pathways. These results suggest that we must be cautious in drawing conclusions about in vivo capsid self-assembly dynamics from theoretical or in vitro models, as the nature of the basic assembly mechanisms accessible to a system can substantially differ between simple and complex model systems, between theoretical models and simulation results, and between in vitro and in vivo assembly conditions.