Using the 2'dG riboswitch as an example this study explains how co-transcriptional folding under kinetic control can be efficiently modeled with ViennaRNA tools
This article focuses on the design rules for de-novo or re-design of riboswitches in synthetic biology applications. We present an efficient approach for the computational prediction of co-transcriptional RNA riboswitch folding in the presence of a ligand. Using the I-A 2’-deoxyguanosine (2’dG)-sensing riboswitch from Mesoplasma florum, which has recently been studied by NMR spectroscopy, as an example we show that our results are in good agreement with experimental data. Computational predictions yield substantial mechanistic insight, allowing us not only to understand natural riboswitches on a mechanistic level but also to perform systematic in silico screening and analysis of novel designs before expensive experimental validation.