1. Evolving methods for rational de novo design of functional RNA molecules.
- Author
-
Hammer, Stefan, Günzel, Christian, Mörl, Mario, and Findeiß, Sven
- Subjects
- *
NON-coding RNA , *SYNTHETIC biology , *MOLECULES , *BIOLOGICAL systems , *OPEN-ended questions - Abstract
• Summarizes commonly used strategies to computationally design functional RNAs. • The complete approach from initial analysis to predictions and wet-lab experiments. • Computational design programs are thoroughly dissected into their algorithmic components. • Experimental methods for design verification and characterization are discussed. Artificial RNA molecules with novel functionality have many applications in synthetic biology, pharmacy and white biotechnology. The de novo design of such devices using computational methods and prediction tools is a resource-efficient alternative to experimental screening and selection pipelines. In this review, we describe methods common to many such computational approaches, thoroughly dissect these methods and highlight open questions for the individual steps. Initially, it is essential to investigate the biological target system, the regulatory mechanism that will be exploited, as well as the desired components in order to define design objectives. Subsequent computational design is needed to combine the selected components and to obtain novel functionality. This process can usually be split into constrained sequence sampling, the formulation of an optimization problem and an in silico analysis to narrow down the number of candidates with respect to secondary goals. Finally, experimental analysis is important to check whether the defined design objectives are indeed met in the target environment and detailed characterization experiments should be performed to improve the mechanistic models and detect missing design requirements. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF