The assembly of picornavirus capsids proceeds through the stepwise oligomerization of capsid protein subunits and depends on interactions between critical residues known as hotspots. Few studies have described the identification of hotspot residues at the protein subunit interfaces of the picornavirus capsid, some of which could represent novel drug targets. Using a combination of accessible web servers for hotspot prediction, we performed a comprehensive bioinformatic analysis of the hotspot residues at the intraprotomer, interprotomer and interpentamer interfaces of the Theiler's murine encephalomyelitis virus (TMEV) capsid. Significantly, many of the predicted hotspot residues were found to be conserved in representative viruses from different genera, suggesting that the molecular determinants of capsid assembly are conserved across the family. The analysis presented here can be applied to any icosahedral structure and provides a platform for in vitro mutagenesis studies to further investigate the significance of these hotspots in critical stages of the virus life cycle with a view to identify potential targets for antiviral drug design.

中文翻译：

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热点残渣的计算机模拟预测，有助于形成小核糖核酸衣壳亚基界面的结构稳定性。

微小RNA病毒衣壳的组装通过衣壳蛋白亚基的逐步寡聚进行，并依赖于称为热点的关键残基之间的相互作用。很少有研究描述在小核糖核酸衣壳蛋白亚基界面处热点残基的鉴定，其中一些可能代表新的药物靶标。使用可访问的Web服务器的组合进行热点预测，我们对Theiler鼠脑脊髓炎病毒（TMEV）衣壳的Protomer，Protomer和Interpentamer接口处的热点残基进行了全面的生物信息学分析。重要的是，发现许多预测的热点残基在不同属的代表性病毒中都是保守的，提示衣壳装配的分子决定因素在整个家族中都是保守的。此处介绍的分析可以应用于任何二十面体结构，并为体外诱变研究提供一个平台，以进一步研究这些热点在病毒生命周期关键阶段的重要性，从而确定抗病毒药物设计的潜在靶标。