Statistical mechanical prediction of ligand perturbation to RNA secondary structure and application to riboswitches,Journal of Computational Chemistry

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Statistical mechanical prediction of ligand perturbation to RNA secondary structure and application to riboswitches
Journal of Computational Chemistry ( IF 3.4 ) Pub Date : 2020-03-27 , DOI: 10.1002/jcc.26195
Osama Alaidi ₁ , Fareed Aboul-Ela ₂

Affiliation

The realization that noncoding RNA is implicated in numerous cellular processes, makes it imperative to understand and predict RNA‐folding. RNA secondary structure prediction is more tractable than tertiary structure or protein structure. Yet insights into RNA structure–function relationships are complicated by coupling between RNA‐folding and ligand‐binding. Here, perturbations to equilibrium secondary structure conformational distributions for two riboswitches are calculated in the presence of bound cognate ligands. This work incorporates a key factor coupling ligand binding to RNA conformation but not considered in most previous calculations: the differential affinity of the ligand for a range of RNA‐folding intermediates. Significant shifts in the free energy landscape (FEL) due to the ligand occur for transcripts of lengths corresponding to the “decision window,” following transcription of the so‐called anti‐terminator helix. The results suggest how ligand perturbation can stabilize the formation of an intermediate conformation, readily facilitating terminator hairpin formation in the full‐length riboswitch.

中文翻译：

配体扰动对 RNA 二级结构的统计力学预测及其在核糖开关中的应用

认识到非编码 RNA 与许多细胞过程有关，因此理解和预测 RNA 折叠势在必行。RNA二级结构预测比三级结构或蛋白质结构更容易处理。然而，由于 RNA 折叠和配体结合之间的耦合，对 RNA 结构 - 功能关系的了解变得复杂。在这里，在结合的同源配体存在的情况下，计算了两个核糖开关的平衡二级结构构象分布的扰动。这项工作结合了与 RNA 构象结合的关键因素偶联配体，但在之前的大多数计算中都没有考虑：配体对一系列 RNA 折叠中间体的不同亲和力。在所谓的抗终止子螺旋的转录之后，对应于“决定窗口”长度的转录本发生了由于配体而导致的自由能景观（FEL）的显着变化。结果表明配体扰动如何稳定中间构象的形成，容易促进全长核糖开关中终止子发夹的形成。

更新日期：2020-03-27

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