Riboswitch can bind small molecules to regulate gene expression. Unlike other RNAs, riboswitch relies on its conformational switching for regulation. However, the understanding of the switching mechanism is still limited. Here, we focussed on the add A-riboswitch to illustrate the dynamical switching mechanism as an example. We performed molecular dynamics simulation, conservation and co-evolution calculations to infer the dynamical motions and evolutionary base pairings. The results suggest that the binding domain is stable for molecule recognition and binding, whereas the switching base pairings are co-evolutionary for translation. The understanding of the add A-riboswitch switching mechanism provides a potential solution for riboswitch drug design.

中文翻译：

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加法A-核糖开关切换机制的计算研究

核糖开关可以结合小分子来调节基因表达。与其他 RNA 不同，核糖开关依赖于其构象转换进行调节。但是，对切换机制的理解仍然有限。在这里，我们将重点放在 add A-riboswitch 上，以举例说明动态切换机制。我们进行了分子动力学模拟、守恒和共同进化计算，以推断动力学运动和进化碱基配对。结果表明，结合域对于分子识别和结合是稳定的，而转换碱基配对对于翻译是共同进化的。对add A-核糖开关开关机制的理解为核糖开关药物设计提供了潜在的解决方案。