Energy landscapes
The energy landscape of an RNA sequence is the set of all its secondary structures with their free energies, connected by elementary moves, i.e. opening or closing one base pair. Its local minima are the structures a molecule can rest in, the saddle points between them set the barriers, and the barrier tree summarises this topology in one diagram. Coarse-graining the landscape into basins turns an astronomically large structure space into a Markov process that can be solved.
The posts begin with the 2002 barrier-tree paper on degenerate landscapes and the lattice protein models that served as test systems, continue with methods for exploring the low-energy part of a landscape efficiently, and end with applications to co-transcriptional folding and RNA design. See energy landscape, barrier tree and saddle point.
Co-transcriptional riboswitch modeling with ViennaRNA
A landscape-based method for modeling how cotranscriptional folding and ligand binding interact in kinetically controlled riboswitches, illustrated with the 2'dG riboswitch from Mesoplasma florum.
In silico design of ligand-triggered RNA switches
A computational workflow for designing ligand-triggered RNA switches, with emphasis on sequence design, folding kinetics, and candidate prioritization.
Co-transcriptional folding and metastable states in riboswitch function
This paper uses NMR spectroscopy to resolve transcription intermediates of the 2'dG riboswitch at single-nucleotide resolution, showing how transcript length and metastable states govern ligand-controlled switching.
Memory-efficient exploration of RNA energy landscapes
This paper revisits the earlier flooding-based landscape methods and adapts them to RNA secondary structures with a local, memory-efficient enumeration strategy.
BarMap and RNA folding on dynamic energy landscapes
BarMap models RNA folding on changing energy landscapes by linking macrostates between landscape snapshots, enabling efficient analysis of co-transcriptional and externally perturbed folding scenarios.