Towards Automated Design of Riboswitches
This work addresses the challenge of reducing costs and time in riboswitch discovery for synthetic biology, though it is incremental as it builds on existing protocols.
The paper tackled the problem of expensive and inefficient experimental screening for novel riboswitches by developing a computational method, libLEARNA, which designs diverse RNA libraries; it resulted in a 30% increase in unique high-quality candidates for theophylline riboswitches.
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.