RNA design
RNA design is the inverse of structure prediction: given a target structure, or a set of structures a molecule should switch between, find a sequence that folds accordingly. The problem is underdetermined, i.e. many sequences fold into the same structure and some targets have no good sequence at all, so design is a search under constraints rather than a calculation. The thermodynamic model scores a candidate at equilibrium; whether it also switches in time has to be checked with a kinetic model, because a sequence can satisfy every structural constraint and still fold too slowly or through the wrong intermediate.
These posts cover ligand-triggered riboswitches designed with explicit kinetic criteria, the use of probing data in design decisions, an essay on mRNA vaccine design, and the rational design of mechanically active RNAs that resist an exoribonuclease, a direction that grew out of the flavivirus xrRNA work. The glossary defines ensemble defect and xrRNA.
Sequence editability of the theophylline RNA aptamer
Molecular dynamics of five theophylline aptamer variants whose binding site is left unchanged: which edits in the surrounding helices keep ligand recognition intact, and which weaken it from the outside.
Rational design of mechanically active RNAs
This Nucleic Acids Research paper shows that synthetic xrRNAs can be designed from topological rules and validated experimentally as mechanically active RNAs.
A first look at rational design of mechanically active RNAs
A preprint-stage note on the design logic behind synthetic xrRNAs and mechanically active RNAs.
Strukturierte RNAs in Viren (in German)
In this mini-review we discuss the concept of RNA structure conservation in viruses, using exoribonuclease-resistant RNAs from flaviviruses as prominent examples
The link between mRNA vaccine design and barbeque optimization
A short podcast appearance on optimization, data sharing, and what mRNA design can teach us about iterative engineering problems.