Rapid and accurate determination of atomistic RNA dynamic ensemble models using NMR and structure prediction.

Journal Article (Journal Article)

Biomolecules form dynamic ensembles of many inter-converting conformations which are key for understanding how they fold and function. However, determining ensembles is challenging because the information required to specify atomic structures for thousands of conformations far exceeds that of experimental measurements. We addressed this data gap and dramatically simplified and accelerated RNA ensemble determination by using structure prediction tools that leverage the growing database of RNA structures to generate a conformation library. Refinement of this library with NMR residual dipolar couplings provided an atomistic ensemble model for HIV-1 TAR, and the model accuracy was independently supported by comparisons to quantum-mechanical calculations of NMR chemical shifts, comparison to a crystal structure of a substate, and through designed ensemble redistribution via atomic mutagenesis. Applications to TAR bulge variants and more complex tertiary RNAs support the generality of this approach and the potential to make the determination of atomic-resolution RNA ensembles routine.

Full Text

Duke Authors

Cited Authors

  • Shi, H; Rangadurai, A; Abou Assi, H; Roy, R; Case, DA; Herschlag, D; Yesselman, JD; Al-Hashimi, HM

Published Date

  • November 2, 2020

Published In

Volume / Issue

  • 11 / 1

Start / End Page

  • 5531 -

PubMed ID

  • 33139729

Pubmed Central ID

  • PMC7608651

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-020-19371-y


  • eng

Conference Location

  • England