A guide to computational cotranscriptional folding featuring the SRP RNA

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. ### Competing Interest Statement The authors have declared no competing interest.