Cited by 38DNA and Nucleic Acid ChemistryProtein Structure and DynamicsAdvanced biosensing and bioanalysis techniques

From a structural average to the conformational ensemble of a DNA bulge

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Shi, Xuesong, Beauchamp, Kyle A., Harbury, Pehr B., Herschlag, Daniel·2014·Proceedings of the National Academy of Sciences

Abstract

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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  1. [36]Carlin BP, Louis TA. The Empirical Bayes Approach. Bayes and Empirical Bayes Methods for Data Analysis. 2nd Ed. London: Chapman & Hall; 2000. [Google Scholar]
  2. [53]Wang JM, Cieplak P, Kollman PA. How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules? J Comput Chem. 2000;21(12):1049–1074. [Google Scholar]

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
Published
2014-03-31
Volume
111
Issue
15
Pages
E1473-80
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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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