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Updated: Sep 25, 2025

Combining X-Ray Crystallography with Small Angle X-Ray Scattering to Model Unstructured Regions of Nsa1 from S. Cerevisiae
Published on: January 10, 2018
Conformational heterogeneity of UCAAUC RNA oligonucleotide from molecular dynamics simulations, SAXS, and NMR
Christina Bergonzo1, Alexander Grishaev1, Sandro Bottaro2,3
1National Institute of Standards and Technology and Institute for Bioscience and Biotechnology Research, Rockville, Maryland 20850, USA.
Abstract:
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.
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