Beyond Plug and Pray: Context Sensitivity and in silico Design of Artificial Neomycin Riboswitches

Computational Approaches for RNA Structure Ensemble Deconvolution from Structure Probing Data

“…However, pioneering work by McCaskill enabled efficient computation of the partition function and the probabilities of observing each potential base pair in the ensemble under the thermodynamic model, 47 thereby greatly expanding the sophistication and scope of computational structure analysis. [48][49][50][51][52][53][54][55][56][57] Methods that leverage the thermodynamic model to obtain more detailed representations of the ensemble in the form of explicit suboptimal secondary structures were also developed. For example, it is possible to compute all the suboptimal secondary structures within a (small) energy increment from the MFE.…”

Cell-free riboswitches

“…49,50 The scarcity of engineered riboswitches that are transcriptionally regulated also extends to E. coli and other bacteria, with only a handful of such riboswitches reported. [51][52][53][54][55][56] This could partly be due to the fact that Gram-negative bacteria, including E. coli, seem to prefer translationally regulated riboswitches, whereas Gram-positive bacteria favor transcriptionally regulated ones. 5,7,57,58 Genes of the Gram-positive bacteria are more frequently organized in larger polycistronic operons which are regulated more efficiently by transcriptionally regulated riboswitches.…”

RNAxplorer: harnessing the power of guiding potentials to sample RNA landscapes

“…For instance, experimentally derived NMR structures ( Helmling et al , 2017 ) have been used to model concentration-dependent metabolite binding/unbinding kinetics ( Wolfinger et al , 2018 ). Furthermore, kinetic methods are invoked in rational design of artificial riboswitches ( Günzel et al , 2020 ). Folding dynamics can also be modeled on the level of tertiary structures, e.g.…”