Department of Theoretical Chemistry, University of Vienna, Vienna, Austria.
Methods Mol Biol. 2024;2726:315-346. doi: 10.1007/978-1-0716-3519-3_13.
Although RNA molecules are synthesized via transcription, little is known about the general impact of cotranscriptional folding in vivo. We present different computational approaches for the simulation of changing structure ensembles during transcription, including interpretations with respect to experimental data from literature. Specifically, we analyze different mutations of the E. coli SRP RNA, which has been studied comparatively well in previous literature, yet the details of which specific metastable structures form as well as when they form are still under debate. Here, we combine thermodynamic and kinetic, deterministic, and stochastic models with automated and visual inspection of those systems to derive the most likely scenario of which substructures form at which point during transcription. The simulations do not only provide explanations for present experimental observations but also suggest previously unnoticed conformations that may be verified through future experimental studies.
尽管 RNA 分子是通过转录合成的，但人们对共转录折叠在体内的普遍影响知之甚少。我们提出了不同的计算方法来模拟转录过程中结构构象的变化，包括对文献中实验数据的解释。具体来说，我们分析了大肠杆菌 SRP RNA 的不同突变，该 RNA 在以前的文献中已经得到了比较好的研究，但关于哪些亚稳定结构形成以及何时形成，仍存在争议。在这里，我们将热力学和动力学、确定性和随机性模型结合起来，并对这些系统进行自动和可视化检查，以得出在转录过程中的哪个时间点形成哪些亚结构的最可能场景。这些模拟不仅为当前的实验观察提供了解释，还提出了以前未注意到的构象，这些构象可能通过未来的实验研究得到验证。
