  RNA function is intimately related to its structural dynamics. Molecular
dynamics simulations are useful for exploring biomolecular flexibility but are
severely limited by the accessible timescale. Enhanced sampling methods allow
this timescale to be effectively extended in order to probe
biologically-relevant conformational changes and chemical reactions. Here, we
review the role of enhanced sampling techniques in the study of RNA systems. We
discuss the challenges and promises associated with the application of these
methods to force-field validation, exploration of conformational landscapes and
ion/ligand-RNA interactions, as well as catalytic pathways. Important technical
aspects of these methods, such as the choice of the biased collective variables
and the analysis of multi-replica simulations, are examined in detail. Finally,
a perspective on the role of these methods in the characterization of RNA
dynamics is provided.
