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Simultaneous NMR characterisation of multiple minima in the free energy landscape of an RNA UUCG tetraloop

Borkar, Aditi N.; Vallurupalli, Pramodh; Camilloni, Carlo; Kay, Lewis E.; Vendruscolo, Michele


Pramodh Vallurupalli

Carlo Camilloni

Lewis E. Kay

Michele Vendruscolo


© the Owner Societies 2017. RNA molecules in solution tend to undergo structural fluctuations of relatively large amplitude and to populate a range of different conformations some of which with low populations. It is still very challenging, however, to characterise the structures of these low populated states and to understand their functional roles. In the present study, we address this problem by using NMR residual dipolar couplings (RDCs) as structural restraints in replica-averaged metadynamics (RAM) simulations. By applying this approach to a 14-mer RNA hairpin containing the prototypical UUCG tetraloop motif, we show that it is possible to construct the free energy landscape of this RNA molecule. This free energy landscapes reveals the surprisingly rich dynamics of the UUCG tetraloop and identifies the multiple substates that exist in equilibrium owing to thermal fluctuations. The approach that we present is general and can be applied to the study of the free energy landscapes of other RNA or RNA-protein systems.


Borkar, A. N., Vallurupalli, P., Camilloni, C., Kay, L. E., & Vendruscolo, M. (2017). Simultaneous NMR characterisation of multiple minima in the free energy landscape of an RNA UUCG tetraloop. Physical Chemistry Chemical Physics, 19(4), 2797-2804.

Journal Article Type Article
Acceptance Date Dec 20, 2016
Online Publication Date Dec 20, 2016
Publication Date Jan 28, 2017
Deposit Date Jun 8, 2020
Journal Physical Chemistry Chemical Physics
Print ISSN 1463-9076
Electronic ISSN 1463-9084
Publisher Royal Society of Chemistry
Peer Reviewed Peer Reviewed
Volume 19
Issue 4
Pages 2797-2804
Public URL
Publisher URL!divAbstract