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Quantifying the local resolution of cryo-EM density maps

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Abstract

We propose a definition of local resolution for three-dimensional electron cryo-microscopy (cryo-EM) density maps that uses local sinusoidal features. Our algorithm has no free parameters and is applicable to other imaging modalities, including tomography. By evaluating the local resolution of single-particle reconstructions and subtomogram averages for four example data sets, we report variable resolution across a 4- to 40-Å range.

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Figure 1: Local resolution.
Figure 2: ResMap-H2 results using experimental density maps.

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Acknowledgements

We are grateful to S. Scheres, G. Lander, A. Bartesaghi and K. Davies for stimulating discussions and sharing their density maps for this study. This work was supported by Natural Sciences and Engineering Research Council of Canada award PGS-D3 (A.K.) and US National Institutes of Health grants R01LM010142 (H.D.T.), R01GM095658 (A.K. and H.D.T.) and R01NS021501 (F.J.S.).

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, Yale University, New Haven, Connecticut, USA

    Alp Kucukelbir, Fred J Sigworth & Hemant D Tagare

  2. Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut, USA

    Fred J Sigworth

  3. Department of Diagnostic Radiology, Yale University, New Haven, Connecticut, USA

    Hemant D Tagare

Authors
  1. Alp Kucukelbir
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  2. Fred J Sigworth
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  3. Hemant D Tagare
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Contributions

A.K. and H.D.T. conceived of the theory. A.K. developed the algorithm and performed experiments. A.K., F.J.S. and H.D.T. designed the experiments and wrote the manuscript.

Corresponding author

Correspondence to Hemant D Tagare.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–5 and Supplementary Notes 1–4 (PDF 4308 kb)

Supplementary Software

The Python source code of our software package ResMap. You may find the latest Mac, Linux, and Windows binaries and the user manual at http://resmap.sourceforge.net (ZIP 42 kb)

A close-up visualization of ResMap-H2 results under varying surface

A close-up visualization of the sub-tomogram reconstruction of GroEL (EMD-2221). The surface is colored using ResMap-H2 results and its threshold is being varied between values 1 and 1.8 (arbitrary units). A docked atomic model is visible through the surface for ease of interpretation. ResMap results point to parts of the alpha helix being resolved to different levels, which is visually corroborated as the surface threshold is varied. (MOV 11493 kb)

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Kucukelbir, A., Sigworth, F. & Tagare, H. Quantifying the local resolution of cryo-EM density maps. Nat Methods 11, 63–65 (2014). https://doi.org/10.1038/nmeth.2727

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