Exploring the multiple conformational states of RNA genome through interhelical dynamics and network analysis

Abstract

The structural variation of RNA is often very transient and can be easily missed in experiments. Molecular dynamics simulation studies along with network analysis can be an effective tool to identify prominent conformations of such dynamic biomolecular systems. Here we describe a method to effectively sample different RNA conformations at six different temperatures based on the changes in the interhelical orientations. This method gives the information about prominent states of the RNA as well as the probability of the existence of different conformations and their interconnections during the process of evolution. In the case of the SARS-CoV-2 genome, the change of prominent structures was found to be faster at 333 K as compared to higher temperatures due to the formation of the non-native base pairs. ΔΔG calculated between 288 K and 363 K are found to be 10.31 kcal/mol (88 nt) considering the contribution from the multiple states of the RNA which agrees well with the experimentally reported denaturation energy for E. coli α mRNA pseudoknot (∼16 kcal/mol, 112 nt) determined by calorimetry/UV hyperchromicity and human telomerase RNA telomerase (4.5–6.6 kcal/mol, 54 nt) determined by FRET analysis. © 2022 Elsevier Inc.