On the Use of Coarse-Grained Thermodynamic Landscapes to Efficiently Estimate Folding Kinetics for RNA Molecules

Abstract

RNA folding pathways play an important role in various biological processes, such as 1) the conformational switch in spliced leader RNA from Leptomonas collosoma, which controls transsplicing of a portion of the 5’ exon, and 2) riboswitches–portions of the 5’ untranslated region of mRNA that regulate genes by allostery. Since RNA folding pathways are determined by the thermodynamic landscape, we have developed a number of novel algorithms—including FFTbor and FFTbor2D—which efficiently compute the coarse-grained energy landscape for a given RNA sequence. These energy landscapes can then be used to produce a model for RNA folding kinetics that can compute both the mean first passage time (MFPT) and equilibrium time in a deterministic and efficient manner, using a new software package we call Hermes. The speed of the software provided within Hermes—namely FFTmfpt and FFTeq—present what we believe to be the first suite of kinetic analysis tools for RNA sequences that are suitable for high throughput usage, something we believe to be of interest in the field of synthetic design.