Model-based analysis of assembly kinetics for virus capsids or other spherical polymers
Model-based analysis of assembly kinetics for virus capsids or other spherical polymers
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DOI：
10.1016/s0006-3495(02)75245-4
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发表时间：
2002-08-01
影响因子：
3.4
通讯作者：
Zlotnick, A
中科院分区：
文献类型：
--
作者：
Endres, D;Zlotnick, A
病毒衣壳或其他球形聚合物的组装由数百个蛋白质亚基组成的空的封闭结构知之甚少。封闭球形聚合物的组装不同于末端开放聚合物的实例的细丝或晶体的聚合。必须考虑这一点，以进行有实际意义的分析。我们已经开发了一个模型的衣壳组装，级联的低阶反应的基础上，使我们能够计算动力学模拟。该模型的行为类似于在溶液中观察到的组装动力学（Zlotnick，A.，J. M.约翰逊，P.W.温菲尔德，S.斯塔尔和D.恩德雷斯1999.生物化学。38：14644-14652）。我们展示了两个例子，这个一般模型描述组装的十二面体和二十面体衣壳。使用基于这些例子的模拟，我们演示了如何从可访问的实验数据中提取组装参数的鲁棒估计。这些参数，核大小，平均成核速率，和平均自由能的协会可以确定从测量的亚基和衣壳的时间和浓度变化。附录中提供了对一般模型进行分析的数学推导。本文中开发的衣壳组装的理解是一般性的，提供的例子可以很容易地修改，以反映不同的生物系统。这种对病毒组装的增强理解将允许对影响组装的病毒稳定性和生物或抗病毒因素进行更定量的分析。
The assembly of virus capsids or other spherical polymers-empty, closed structures composed of hundreds of protein subunits-is poorly understood. Assembly of a closed spherical polymer is unlike polymerization of a filament or crystal, examples of open-ended polymers. This must be considered to develop physically meaningful analyses. We have developed a model of capsid assembly, based on a cascade of low-order reactions, that allows us to calculate kinetic simulations. The behavior of this model resembles assembly kinetics observed in solution (Zlotnick, A., J. M. Johnson, P. W. Wingfield, S. J. Stahl, and D. Endres. 1999. Biochemistry. 38:14644-14652). We exhibit two examples of this general model describing assembly of dodecahedral and icosahedral capsids. Using simulations based on these examples, we demonstrate how to extract robust estimates of assembly parameters from accessible experimental data. These parameters, nucleus size, average nucleation rate, and average free energy of association can be determined from measurement of subunit and capsid as time and concentration vary. Mathematical derivations of the analyses, carried out for a general model, are provided in an Appendix. The understanding of capsid assembly developed in this paper is general; the examples provided can be readily modified to reflect different biological systems. This enhanced understanding of virus assembly will allow a more quantitative analysis of virus stability and biological or antiviral factors that affect assembly.