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Center for Nonlinear Studies |
Within all living cells, processes of viral replication, metabolite sensing, and transcription/translation all hinge on the folding of RNA molecules, from small stem-loops to large ribosomal fragments. The physico-chemical environment plays important roles in RNA folding, particularly at equilibrium, where experiments show stabilization of RNA duplexes by hydrostatic pressure, and shifts in equilibrium to alternative states or secondary structure disruption by cosolutes. Only in recent years, and with significantly modified all-atom force field parameters, has characterization of RNA thermodynamics become feasible and made it possible to explore questions in RNA equilibrium, including the effects of pressure and cosolutes. By applying high performance computation to a model hyperstable RNA tetraloop, and varying hydrostatic pressures and denaturant concentrations, the free energy landscapes of a basic RNA motif are characterized at atomic detail. Prominent observations include the emergence of multiple native and non-native ensembles that recapitulate a plethora of experimental results.