On the Power and Challenges of Atomistic Molecular Dynamics to Investigate RNA Molecules

RNA molecules play a vital role in biological processes within the cell, with significant implications for science and medicine. Notably, the biological functions exerted by specific RNA molecules are often linked to the RNA conformational ensemble. However, the experimental characterization of such three-dimensional RNA structures is challenged by the structural heterogeneity of RNA and by its multiple dynamic interactions with binding partners such as small molecules, proteins, and metal ions. Consequently, our current understanding of the structure–function relationship of RNA molecules is still limited. In this context, we highlight molecular dynamics (MD) simulations as a powerful tool to complement experimental efforts on RNAs. Despite the recognized limitations of current force fields for RNA MD simulations, examining the dynamics of selected RNAs has provided valuable functional insights into their structures.