Towards Automated Design of Riboswitches

TL;DR

This paper introduces libLEARNA, a novel computational method for designing diverse, high-quality riboswitch libraries that improve candidate yield and reduce experimental screening costs.

Contribution

The work presents a new structure-based design approach for riboswitches, enabling the creation of diverse candidate libraries with enhanced quality and quantity.

Findings

30% more unique high-quality candidates produced

Designs follow established protocols for theophylline riboswitches

Method reduces costs and time in riboswitch discovery

Abstract

Experimental screening and selection pipelines for the discovery of novel riboswitches are expensive, time-consuming, and inefficient. Using computational methods to reduce the number of candidates for the screen could drastically decrease these costs. However, existing computational approaches do not fully satisfy all requirements for the design of such initial screening libraries. In this work, we present a new method, libLEARNA, capable of providing RNA focus libraries of diverse variable-length qualified candidates. Our novel structure-based design approach considers global properties as well as desired sequence and structure features. We demonstrate the benefits of our method by designing theophylline riboswitch libraries, following a previously published protocol, and yielding 30% more unique high-quality candidates.