StraD: a coarse-grained simulation of co-transcriptional RNA folding

Co-transcriptional folding is a fundamental process in living cells. Since transient RNA structures that appear during transcription have crucial functions like molecular recognition in riboswitches, elucidating the mechanism of co-transcriptional folding is an important issue to comprehend RNA functions. In the present paper, we propose a novel algorithm, StraD, for RNA secondary structure kinetics simulation on a coarse-grained energy landscape. StraD explores an energy landscape where secondary structures are enumerated based on a constrained local flooding algorithm. The constraint and local search approach effectively reduces the number of conformations in the enumeration process, enabling StraD to perform efficient flooding-based simulations. We applied StraD to co-transcriptional folding simulations of artificial RNA switches. We found that the simulation results for the artificial RNA switches reproduced those by a fine-grained simulation method, Kinfold. Moreover, with Kinfold and StraD, we performed co-transcriptional folding simulation of <i>Saccharomyces cerevisiae</i> tRNAs and 5S rRNAs and found that suboptimal secondary structures obtained after the simulations include accurate structures.