Conformational heterogeneity of UCAAUC RNA oligonucleotide from molecular dynamics simulations, SAXS, and NMR experiments

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  • Christina Bergonzo
  • Alexander Grishaev
  • Sandro Bottaro

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.

OriginalsprogEngelsk
TidsskriftRNA
Vol/bind28
Udgave nummer7
Sider (fra-til)937-946
Antal sider10
ISSN1355-8382
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
We would like to thank Giovanni Bussi and Kresten Lindorff-Larsen for useful discussions. Certain commercial equipment, instruments, and materials are identified in this paper in order to specify the experimental procedure. Such identification does not imply recommendation or endorsement by the National Institute of Standards and Technology, nor does it imply that the material or equipment identified is necessarily the best available for the purpose. S.B. acknowledges funding from the Lundbeck Foundation BRAINSTRUC structural biology initiative (R155-2015-2666).

Publisher Copyright:
© 2022 Bergonzo et al.

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