Modeling Conformational Flexibility and Evolution of Structure: RNA as an Example

In this chapter, RNA secondary structures are used as an appropriate toy model to illustrate an application of the landscape concept to understand the molecular basis of structure formation, optimization, adaptation, and evolution in simple systems. Two classes of landscapes are considered (1) conformational landscapes mapping RNA conformations into free energies of formation and (2) sequence–structure mappings assigning minimum free energy structures to sequences. Even without referring to suboptimal conformations, optimization of RNA structures by mutation and selection reveals interesting features on the population level that can be interpreted by means of sequence–structure maps. The full power of the RNA model unfolds when sequence–structure maps and conformational landscapes are merged into a more advanced mapping that assigns a whole spectrum of conformations to the individual sequence. The scenario is complicated further – but at the same time made more realistic – by considering kinetic effects that allow for the assignment of two or more long-lived conformations, together with their suboptimal folds, to a single sequence. In this case, molecules can be designed, which fulfil multiple functions by switching back and forth from one stable conformation to the other or by changing conformation through allosteric binding of effectors. The evolution of noncoding RNAs is presented as an example for the application of landscape-based concepts.

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