Deciphering the kinetic mechanism of spontaneous self-assembly of icosahedral capsids
Deciphering the kinetic mechanism of spontaneous self-assembly of icosahedral capsids
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DOI：
10.1021/nl062449h
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发表时间：
2007-02-01
期刊：
影响因子：
10.8
通讯作者：
Brooks, Charles L., III
中科院分区：
文献类型：
--
作者：
Nguyen, Hung D.;Reddy, Vijay S.;Brooks, Charles L., III
病毒蛋白自组装成二十面体衣壳是一个有趣但知之甚少的现象，阐明这一现象可能有助于探索衣壳在材料科学和医学中的有益应用。使用粗粒模型的衣壳蛋白的分子动力学模拟，我们表明，完整的衣壳和非理想化结构的形成之间的竞争是强烈依赖于蛋白质的浓度和温度，发生动力学作为一个级联的基本反应，其中自由单体被添加到不断增长的低聚物上的下坡自由能景观。然而，最终亚基的插入是病毒衣壳组装中限速的、能量上不利的步骤。已构建相图，以显示在每个浓度和温度下衣壳或非理想化结构稳定的区域。我们预计，我们的研究结果将提供指导，在确定合适的条件下所需的体外病毒衣壳组装实验。
Self-assembly of viral proteins into icosahedral capsids is an interesting yet poorly understood phenomenon of which elucidation may aid the exploration of beneficial applications of capsids in materials science and medicine. Using molecular dynamics simulations of coarse-grained models for capsid proteins, we show that the competition between the formation of full capsids and nonidealized structures is strongly dependent upon the protein concentration and temperature, occurring kinetically as a cascade of elementary reactions in which free monomers are added to the growing oligomers on a downhill free-energy landscape. However, the insertion of the final subunits is the rate-limiting, energetically unfavorable step in viral capsid assembly. A phase diagram has been constructed to show the regions where capsids or nonidealized structures are stable at each concentration and temperature. We anticipate that our findings will provide guidance in identifying suitable conditions required for in vitro viral capsid assembly experiments.