Shape similarity measures for the design of small RNA switches
Shape similarity measures for the design of small RNA switches
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DOI：
10.1080/07391102.2006.10507094
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发表时间：
2006-08-01
影响因子：
4.4
通讯作者：
Barash, Danny
中科院分区：
文献类型：
--
作者：
Avihoo, Assaf;Barash, Danny
RNA二级结构中的构象转换最近引起了相当大的关注，这是由于在生物体中发现了“核糖开关”。这些是在细菌中发现的遗传控制元件，并提供了一种独特的调节机制，该机制基于在两种高度稳定的状态之间切换，这两种状态之间被能量屏障隔开。在核糖开关中，能量屏障被直接代谢物结合穿过，这促进了通过变构手段的调节。然而，其他事件触发因素也可能导致转换发生，例如单点突变和温度的轻微变化。具有这些事件触发器的开关的示例在过去已经实验性地报道。在这里，目标是通过计算设计依赖于这些触发器的小RNA开关。为此，我们的计算机模拟利用各种不同的相似性措施来评估初始状态和触发状态之间的距离，基于二级结构本身的拓扑结构。我们描述了这些组合的相似性措施，依赖于粗粒度和细粒度的RNA二级结构的图形表示。作为我们模拟的结果，我们提供了一些大约30-50 nt的候选序列，沿着驱动转换的确切触发物。所考虑的事件触发器可以通过Zuker的mfold或维也纳包来建模。所提出的依赖于形状测量的方法可以进一步用于通过模拟各种事件触发器并计算它们对形状的影响来计算地生成更多候选。
Conformational switching in the secondary structure of RNAs has recently attracted considerable attention, fostered by the discovery of 'riboswitches' in living organisms. These are genetic control elements that were found in bacteria and offer a unique regulation mechanism based on switching between two highly stable states, separated by an energy barrier between them. In riboswitches, the energy barrier is crossed by direct metabolite binding, which facilitates regulation by allosteric means. However, other event triggers can cause switching to occur, such as single-point mutations and slight variations in temperature. Examples of switches with these event triggers have already been reported experimentally in the past. Here, the goal is to computationally design small RNA switches that rely on these,triggers. Towards this end, our computer simulations utilize a variety of different similarity measures to assess the distances between an initial state and triggered states, based on the topology of the secondary structure itself. We describe these combined similarity measures that rely on both coarse-grained and fine-grained graph representations of the RNA secondary structure. As a result of our simulations, we provide some candidate sequences of approximately 30-50 nt, along with the exact triggers that drive the switching. The event triggers under consideration can be modelled by Zuker's mfold or the Vienna package. The proposed methodology that rely on shape measures can further be used to computationally generate more candidates by simulating various event triggers and calculating their effect on the shape.