Metal cations and RNA - a highly charged problem with a dynamic future

Metal cations are essential for RNA folding and function, two interlinked and vitally important processes. The mechanism by which cations regulate these processes has promising medical and biotechnological applications: Gaining detailed insight allows us to make targeted use of cations to manipulate structure formation, biological function, and even gene expression or to build functional RNA nanomaterial within a cell.

Resolving the role of metal cations is challenging experimentally since the resolution even of state of the art techniques is insufficient to characterize the exact interactions. Here, computational methods can contribute significant insight. As a first step to quantitatively describe cation-RNA interaction, we develop optimized force field parameters for mono- and divalent metal cations. The optimized parameters allow us to capture the fine differences between distinct metal cations including specific ion binding affinities and the kinetics of cation binding to the backbone of RNA and to the nucleobases.
In a second step, we investigate the role of different metal cations in systems of increasing complexity ranging from basic structural motifs to regulatory RNA elements.