4.5 Article

Developments in solution-state NMR yield broader and deeper views of the dynamic ensembles of nucleic acids

Journal

CURRENT OPINION IN STRUCTURAL BIOLOGY
Volume 70, Issue -, Pages 16-25

Publisher

CURRENT BIOLOGY LTD
DOI: 10.1016/j.sbi.2021.02.007

Keywords

Solution state NMR; Nucleic acids; Dynamic ensembles; Excited

Funding

  1. NIAID NIH HHS [R21 AI143460, R21 AI149112, U54 AI150470] Funding Source: Medline
  2. NIGMS NIH HHS [P50 GM103297, R01 GM089846, R01 GM132899] Funding Source: Medline

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Recent advances in solution-state nuclear magnetic resonance (NMR) methods, integrated with computational techniques, have improved the ability to probe the dynamic ensembles of DNA and RNA, leading to new mechanistic insights into gene expression and regulation.
Nucleic acids do not fold into a single conformation, and dynamic ensembles are needed to describe their propensities to cycle between different conformations when performing cellular functions. We review recent advances in solution-state nuclear magnetic resonance (NMR) methods and their integration with computational techniques that are improving the ability to probe the dynamic ensembles of DNA and RNA. These include computational approaches for predicting chemical shifts from structure and generating conformational libraries from sequence, measurements of exact nuclear Overhauser effects, development of new probes to study chemical exchange using relaxation dispersion, faster and more sensitive real-time NMR techniques, and new NMR approaches to tackle large nucleic acid assemblies. We discuss how these advances are leading to new mechanistic insights into gene expression and regulation.

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