Modeling Kinetics of RNA RNA Interactions on Direct Paths
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Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.28.548983v1?rss=1

Authors: Waldl, M., Beckmann, I. K., Will, S., Hofacker, I. L.

Abstract: Interactions between RNAs are an essential mechanism in gene regulation. State-of-the-art tools predict RNA-RNA interactions based on thermodynamic stability but largely neglect kinetic effects. To overcome this limitation, we propose novel models of RNA-RNA interaction dynamics. On this basis we can improve our understanding of general principles that govern RNA-RNA interaction formation and improve target prediction tools. While the dynamics of secondary structure formation of single RNAs have been successfully modeled using transition systems between conformations, analogous approaches for RNA-RNA interaction quickly lead to infeasibly large systems. Therefore, we propose reducing the interaction system to the direct trajectories (shortest paths) from possible first contacts to full hybridization. This key idea enables studying general principles and relevant features of the interaction formation as well as model details; e.g. the relative speed of intra- and intermolecular folding. Due to the design of our RNA kinetics model, features like energy barriers can be computed efficiently. In the future, this could enable refining genome-wide target predictions through kinetic criteria. Beyond these immediate practical improvements, it could shed light on general principles like the long-debated influence of the accessibility of the initial contact site. RRIkinDP is is available on GitHub at https://github.com/mwaldl/RRIkinDP.

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