Conformational Heterogeneity of UCAAUC RNA Oligonucleotide from Molecular Dynamics Simulations, SAXS, and NMR experiments

We describe the conformational ensemble of the single-stranded r(UCAAUC) oligonucleotide obtained using extensive molecular dynamics (MD) simulations and ROSETTA's FARFAR2 algorithm. The conformations observed in MD consist of A-form-like structures and variations thereof. These structures are not present in the pool generated using FARFAR2. By comparing with available NMR measurements, we show that the presence of both A-form-like and other extended conformations is necessary to quantitatively explain experimental data. To further validate our results, we measure SAXS data on the RNA hexamer and find that simulations result in more compact structures than observed from these experiments. The integration of simulations with NMR via a maximum entropy approach shows that small modifications to the MD ensemble lead to an improved description of the conformational ensemble. Nevertheless, we identify persisting discrepancies in matching experimental SAXS data.