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To function as gene regulatory elements in response to environmental signals, riboswitches must adopt specific secondary structures on appropriate time scales. We employ kinetic Monte Carlo simulation to model the time-dependent folding during transcription of TPP riboswitch expression platforms. According to our simulations, riboswitch transcriptional terminators, which must adopt a specific hairpin configuration by the time they have been transcribed, fold with higher efficiency than Shine-Dalgarno sequesterers, whose proper structure is required only at the time of ribosomal binding. Our findings suggest both that riboswitch transcriptional terminator sequences have been naturally selected for high folding efficiency, and that sequesterers can maintain their function even in the presence of significant misfolding.
Understanding protein folding has been one of the great challenges in biochemistry and molecular biophysics. Over the past 50 years, many thermodynamic and kinetic studies have been performed addressing the stability of globular proteins. In comparis
Riboswitches are cis-acting regulatory RNA elements prevalently located in the leader sequences of bacterial mRNA. An adenine sensing riboswitch cis-regulates adeninosine deaminase gene (add) in Vibrio vulnificus. The structural mechanism regulating
We introduce a method for predicting RNA folding pathways, with an application to the most important RNA tetraloops. The method is based on the idea that ensembles of three-dimensional fragments extracted from high-resolution crystal structures are h
The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling approach, an
Energy landscape theory describes how a full-length protein can attain its native fold after sampling only a tiny fraction of all possible structures. Although protein folding is now understood to be concomitant with synthesis on the ribosome there h