Albany 2015:Book of Abstracts
June 9-13 2015
©Adenine Press (2012)
Constructing Free Energy Landscapes of RNAs at Atomic Resolution and Characterisation of their Excited States
Excited states (ES) are structures that have lifetimes typically shorter than milliseconds and populations typically lower than 5%. Particularly for RNA molecules, the existence of excited states has long been anticipated, but we have just started to understand their structures and roles in RNA function. Recent advances in NMR techniques have pointed out that RNA undergoes complex structural dynamics, which make it challenging to characterise the excited states of RNA, let alone isolate the ones that are relevant to its function. In this study, we address this particular problem by using a combination of sub-millisecond dynamics information from NMR residual dipolar couplings and atomic resolution construction of conformational ensembles using molecular dynamics simulations (Borkar et al. 2013) to construct free energy landscapes of RNA. Our results illustrate a rugged free energy landscape for RNA where several excited states exist around the native functional conformation. Our method can be generalised to study the free energy landscapes and dynamical behaviour of different RNA systems to relate their structures to functions. We anticipate that this type of approach could further be used to explore the potential of RNA-based drug therapeutics and improvement of nucleic acid force fields.
Borkar A. N., De Simone A., Montalvao R. W., Vendruscolo M. (2013). A method of determining RNA conformational ensembles using structure-based calculations of residual dipolar couplings. J Chem Phys. 138(21), 215103.
Aditi N. Borkar1*
1Department of Chemistry