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 nuclear magnetic resonance (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 solution X-ray scattering (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.

Automated summary

We describe the conformational ensemble of a single-stranded oligonucleotide using MD simulations and the FARFAR2 algorithm. The presence of A-form-like structures and other extended conformations is necessary to explain experimental data. However, simulations result in more compact structures than observed in experiments. Integration of simulations with NMR data improves the description of the conformational ensemble, but discrepancies with experimental SAXS data persist.