From a structural average to the conformational ensemble of a DNA bulge
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Significance: Obtaining the conformational ensembles of biological macromolecules, beyond average structures, is extremely challenging but necessary for a complete understanding of their folding and functions. Such insights may also lead to the rational design of therapeutics that can target less-ordered macromolecules and may advance the design of nanostructures and nanomachines from nucleic acids. We have applied X-ray interferometry to estimate the conformational ensemble of a small-model macromolecule, a DNA bulge, representative of helix–junction–helix building blocks of natural RNAs and designed DNA nanostructures. The measured ensemble, in combination with molecular dynamics simulations, provides testable atomic-level models. X-ray interferometry is extremely sensitive and can detect changes in the ensemble arising from different bulge sequences and solution salt conditions.
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RNA and DNA exist as conformational ensembles in freely diffusing states, crystals, nucleosomes, ribosomes, and spliceosomes.
“RNA and DNA also exist as conformational ensembles, no matter whether in freely diffusing state,540 in crystal,541 or in large nucleosomes,542 ribosomes, or spliceosomes.”
From Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell (2016) · cites this paper as [541]
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Wei, G., Xi, W., Nussinov, R., & Ma, B. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00562 · Cited by 436 · see citing works
- Authors
- Shi, X., Beauchamp, K. A., Harbury, P. B., & Herschlag, D.
- Affiliations
- Department of Biochemistry and
- Stanford University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-03-31
- Volume
- 111
- Issue
- 15
- Pages
- E1473-80
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3992658
- OpenAlex
- W2140186766
- Cited by
- 38
- References
- 54
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 6 · 2023: 4 · 2022: 1 · 2020: 2 · 2019: 1 · 2018: 5 · 2017: 3 · 2016: 6 · 2015: 7 · 2014: 1
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (DP1OD000429)
- National Institute of General Medical Sciences (P01GM066275)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
- Keywords
- DNA bulges, conformational ensembles, ionic environment, electrostatic effects, stacking interactions, elastic model, molecular dynamics simulation, 2-aminopurine fluorescence, DNA conformational dynamics
- MeSH terms
- Biophysics, DNA, Fluorescence, Gold, Interferometry, Models, Molecular, Nucleic Acid Conformation, Nanostructures, Scattering, Small Angle, Molecular Dynamics Simulation
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