Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Matters Arising
  • Published:

Reply to: Limitations of the iterative electron density reconstruction algorithm from solution scattering data

Nature Methods volume 18, pages 246–248 (2021)Cite this article

Subjects

The Original Article was published on 01 March 2021

replying to P. V. Konarev & D. I. Svergun Nature Methods https://doi.org/10.1038/s41592-021-01082-x (2021)

In their Matters Arising1, Konarev and Svergun claim that several statements made in the original article2 are not accurate, namely that DENSS (DENsity from Solution Scattering) cannot reconstruct multiple-density particles from one-dimensional solution scattering data and that the averaging procedure results in a type of low-pass filter effect that negates the accuracy of the averaged density map. Here I demonstrate that, while three-dimensional (3D) ab initio reconstructions from DENSS must not be overinterpreted, DENSS can indeed reconstruct multi-density particles provided that sufficient contrast differences exist between components, and that the averaging procedure is an effective way to improve the accuracy of the reconstructions.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Calculated or reconstructed low-resolution density of DDM micelles and protein–nucleic acid complexes.

Data availability

The experimental DDM micelle data were kindly provided by F. Gabel and are available as described in ref. 7.

Code availability

DENSS is available open source on GitHub at https://github.com/tdgrant1/denss.git, and instructions for downloading, installing and running DENSS can be found on the GitHub page and at https://www.tdgrant.com/denss/.

References

  1. Konarev, P. V. & Svergun, D. I. Limitations of the iterative electron density reconstruction algorithm from solution scattering data. Nat. Methods https://doi.org/10.1038/s41592-021-01082-x (2021).

  2. Grant, T. D. Ab initio electron density determination directly from solution scattering data. Nat. Methods 15, 191–193 (2018).

    Article  CAS  Google Scholar 

  3. Garavito, R. M. & Ferguson-Miller, S. Detergents as tools in membrane biochemistry. J. Biol. Chem. 276, 32403–32406 (2001).

    Article  CAS  Google Scholar 

  4. Hyland, L. L., Taraban, M. B. & Yu, Y. B. Using small-angle scattering techniques to understand mechanical properties of biopolymer-based biomaterials. Soft Matter https://doi.org/10.1039/C3SM51209F (2018).

  5. Manet, S. et al. Structure of micelles of a nonionic block copolymer determined by SANS and SAXS. J. Phys. Chem. B 115, 11318–11329 (2011).

    Article  CAS  Google Scholar 

  6. Li, T., Senesi, A. J. & Lee, B. Small angle X-ray scattering for nanoparticle research. Chem. Rev. 116, 11128–11180 (2016).

    Article  CAS  Google Scholar 

  7. Gabel, F., Engilberge, S., Perez, J. & Girard, E. Medical contrast media as possible tools for SAXS contrast variation. IUCrJ 6, 521–525 (2019).

    Article  CAS  Google Scholar 

  8. Spahn, C. M., Penczek, P. A., Leith, A. & Frank, J. A method for differentiating proteins from nucleic acids in intermediate-resolution density maps: cryo-electron microscopy defines the quaternary structure of the Escherichia coli 70S ribosome. Structure 8, 937–948 (2000).

    Article  CAS  Google Scholar 

  9. Tang, G. et al. EMAN2: an extensible image processing suite for electron microscopy. J. Struct. Biol. 157, 38–46 (2007).

    Article  CAS  Google Scholar 

  10. Fienup, J. R. & Wackerman, C. C. Phase-retrieval stagnation problems and solutions. J. Opt. Soc. Am. A 3, 1897–1907 (1986).

    Article  Google Scholar 

  11. Wackerman, C. C. & Yagle, A. E. Use of Fourier domain real-plane zeros to overcome a phase retrieval stagnation. J. Opt. Soc. Am. A 8, 1898–1904 (1991).

    Article  Google Scholar 

  12. Cameron, E. A. et al. Multidomain carbohydrate-binding proteins involved in Bacteroides thetaiotaomicron starch metabolism. J. Biol. Chem. 287, 34614–34625 (2012).

    Article  CAS  Google Scholar 

  13. Petoukhov, M. V. & Svergun, D. I. Ambiguity assessment of small-angle scattering curves from monodisperse systems. Acta Crystallogr. D Biol. Crystallogr. 71, 1051–1058 (2015).

    Article  CAS  Google Scholar 

  14. Volkov, V. V. & Svergun, D. I. Uniqueness of ab-initio shape determination in small-angle scattering. J. Appl. Crystallogr. 36, 860–864 (2003).

    Article  CAS  Google Scholar 

  15. Schneidman-Duhovny, D., Hammel, M., Tainer, J. A. & Sali, A. Accurate SAXS profile computation and its assessment by contrast variation experiments. Biophys. J. 105, 962–974 (2013).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The author thanks F. Gabel for providing SAXS data of the DDM micelle7. The author acknowledges support from the BioXFEL NSF Science and Technology Center (NSF 1231306) and from NIH award R01GM133998.

Author information

Authors and Affiliations

  1. Department of Structural Biology, Jacobs School of Medicine and Biomedical Sciences, SUNY University at Buffalo, Buffalo, NY, USA

    Thomas D. Grant

Authors
  1. Thomas D. Grant
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas D. Grant.

Ethics declarations

Competing interests

The author declares no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Grant, T.D. Reply to: Limitations of the iterative electron density reconstruction algorithm from solution scattering data. Nat Methods 18, 246–248 (2021). https://doi.org/10.1038/s41592-021-01083-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41592-021-01083-w

This article is cited by

Search

Advanced search

Quick links

Nature Briefing AI and Robotics

Sign up for the Nature Briefing: AI and Robotics newsletter — what matters in AI and robotics research, free to your inbox weekly.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing: AI and Robotics