Project A11 – Regulating RNA by cations: Insight from MD simulations

Working on this project:

Nadine Schwierz & Team

The aim of project A11 is to investigate the mechanism of regulating RNA by cations using molecular dynamics simulations. In order to provide a thorough understanding of the role of cations in RNA regulation, we use a multidisciplinary approach of combining all-atom molecular dynamics simulations and various experimental techniques including NMR (A1, Schwalbe), time-resolved spectroscopy (A7, Wachtveitl), reversible photoswitching (A6, Heckel), EPR/PELDOR (A3, Prisner), and single-molecule FRET (B12, Hengesbach). In particular, we will focus on three objectives: Aim 1: Development of a quantitative description of cation-RNA interactions by optimizing ionic force field parameters, characterizing ion binding affinities and exchange kinetics and validating against existing experimental data (RNA duplexes from A3 and hammerhead ribozyme from A3 and A10). Aim 2: Characterization of ion selectivity and cation exchange kinetics of an RNA G-quadruplex by combining molecular dynamics simulations and results from NMR experiments (A1) and time-resolved spectroscopy (A7, A6). Aim 3: Identification of the mechanism of cation sensing by the guanidine-II riboswitch by calculating the binding affinity of guanidinium cations based on free energy perturbation simulations and by resolving the energy landscape of the conformational transition in response to changes in the guanidinium concentration using enhanced sampling simulation techniques in close collaboration with experiments (A1, A7, and B12).