Project A9 – Molecular Simulations of RNA Folding and Function

Working on this project:

Gerhard Hummer & Team

In Project A9, we use molecular simulations and modeling to develop a molecular-level understanding of the folding, dynamics, and function of RNA, and to contribute to the design of tools to target RNA regulatory processes. We have used molecular dynamics (MD) simulations of RNA structure and dynamics to guide the design of photo-activated nucleic acids and to interpret spectroscopic experiments. To harness the full power of molecular simulations, we have worked toward accurate force-field descriptions of RNA that make it possible to study RNA folding and dynamics in MD simulations. We have used coarse-grained MD simulations to study riboswitch folding and dynamics, and to resolve large-scale RNA conformational changes. Building on our progress in these areas, we now propose to use molecular simulations and integrative modeling as tools in the elucidation of the structure and dynamics of RNA in vivo (Aim 1). We will develop a platform for the hierarchical assembly of 3D RNA structures using building blocks with accurate local structure. We will apply this approach to study the SMN2 pre-mRNA structure. In Aim 2, we will study RNA dynamics using MD simulations in conjunction with experimental characterizations. We already work in close collaboration with the experimental projects of Schwalbe (A1), Prisner (A3), Heckel (A6), Wachtveitl (A7), and Schuman/Heckel (B11). With the tools developed in the new funding period, we will expand our collaborations to projects on protein-RNA complexes (B7 Tampé and B16 Schlundt).