Cited by 750Enzyme Structure and FunctionProtein Structure and DynamicsNuclear Physics and Applications

Accurate assessment of mass, models and resolution by small-angle scattering

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Rambo, Robert P., Tainer, John A.·2013·Nature

Abstract

Modern small-angle scattering (SAS) experiments with X-rays or neutrons provide a comprehensive, resolution-limited observation of the thermodynamic state. However, methods for evaluating mass and validating SAS-based models and resolution have been inadequate. Here we define the volume of correlation, Vc, a SAS invariant derived from the scattered intensities that is specific to the structural state of the particle, but independent of concentration and the requirements of a compact, folded particle. We show that Vc defines a ratio, QR, that determines the molecular mass of proteins or RNA ranging from 10 to 1,000 kilodaltons. Furthermore, we propose a statistically robust method for assessing model-data agreements (χ(2)free) akin to cross-validation. Our approach prevents over-fitting of the SAS data and can be used with a newly defined metric, RSAS, for quantitative evaluation of resolution. Together, these metrics (Vc, QR, χ(2)free and RSAS) provide analytical tools for unbiased and accurate macromolecular structural characterizations in solution.

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Authors
Rambo, R. P., & Tainer, J. A.
Affiliations
  • Lawrence Berkeley National Laboratory (US)
  • Scripps Research Institute (US)
Corresponding author
  • Rambo, Robert P.
  • Tainer, John A.
Venue
Nature
Published
2013-04
Volume
496
Issue
7446
Pages
477-481
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W1984084102
Cited by
750
References
35
Citations by year
2026: 34 · 2025: 34 · 2024: 39 · 2023: 46 · 2022: 81 · 2021: 57 · 2020: 71 · 2019: 65 · 2018: 64 · 2017: 70 · 2016: 74 · 2015: 53 · 2014: 43 · 2013: 19
FWCI
28.41
Type
journal article
Language
en
Open access
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Cancer Institute (R35CA220430)
  • National Institute of General Medical Sciences (R01GM105404)
Topics
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Physics and Astronomy › Radiation › Nuclear Physics and Applications
Keywords
small-angle scattering, molecular mass estimation, model-data agreement, resolution assessment, model validation, protein complexes, macromolecular flexibility, solution structure
MeSH terms
DNA-Binding Proteins, Models, Chemical, Models, Molecular, Molecular Conformation, Molecular Weight, RNA, Viral, Solutions, Reproducibility of Results, RNA-Binding Proteins, Pliability, Aldose-Ketose Isomerases, Scattering, Small Angle, Riboswitch

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