Formalization of RNA folding

Hello! I am a student who recently started playing Eterna and want to ask you guys a question about the formalization of RNA folding. Certain bases appear to be more critical “nodes” in determining the structure, whereas others are more flexible ones whose identity can be tweaked without as drastic an effect. It is somewhat similar to how people sometimes view intrinsically disordered regions in proteins, where particular regions are particularly sensitive to mutations (ie, are more critical “nodes”) and others are less so (this study).

Is there currently a way to formalize this sort of hierarchy of structure, say, in terms of the bases and the locations of those bases with respect to one another? From how the game’s presented, it looks like much of the modeling of structure is based on free energy minimization. But I’d be very curious if there’ve been other formalizations (eg, those that have fleshed out basic RNA folding principles that Eterna players have converged on).

I ask because it seems it would be simpler to do this for RNA since, at least as I understand it, the folding is generated by discrete base-pairing rules. whereas with for example proteins or chromosomes, the interaction “units” are larger (eg, groups of amino acids) and so maybe more difficult to “handle” from a modeling perspective.

Thanks and look forward to any thoughts!

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