ArticleProgress in biophysics and molecular biology2020
Non-uniformity of projection distributions attenuates resolution in Cryo-EM.
Article in Progress in biophysics and molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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49 citing papers in PubMed, 69 citations in OpenAlex.
- The CAHRA Challenge: A Community-Wide Assessment of Cryo-EM Heterogeneous Reconstruction Algorithms.bioRxiv : the preprint server for biology · 2026Article
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- Structural basis of step II spliced leader RNA trans-splicing in trypanosomatid parasites.Nature communications · 2026Article
- Carbon nanotubes as the supporting film for cryo-EM specimen preparation.Nature communications · 2026Article
- Hydrophobic unnatural base pair promotes trigger loop closure and catalysis in cellular RNA polymerase independent of hydrogen bonding.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Two datasets are better than one: method of double moments for 3D reconstruction in cryo-EM.Inverse problems · 2026Article
- Diversifying particle-orientation distributions in cryo-EM with LEA protein additives.bioRxiv : the preprint server for biology · 2026Article
- Structural flexibility of the human vault particle revealed by high-resolution cryo-EM and molecular dynamics simulations.Nature communications · 2026Article
- Supercoiled DNA recognition and cleavage control in topoisomerase VI.Nature communications · 2026Article
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- Ultrathin liquid cells for microsecond time-resolved cryo-EM.Nature communications · 2026Article
- Cryo-EM structure of the human COP1-DET1 ubiquitin ligase complex.Nature communications · 2026Article
- Mechanism of SARS-CoV-2 resistance to nucleotide analog-based antivirals.Nature communications · 2026Article
- Subspace Method of Moments forSIAM journal on imaging sciences · 2026Article
- Transcription co-inhibition alters drug resistance evolution and enhances Mycobacterium tuberculosis clearance from granulomas.Nature microbiology · 2026Article
- Structural basis of undecaprenyl phosphate glycosylation leading to polymyxin resistance in Gram-negative bacteria.Nature communications · 2025Article
- Structural and catalytic diversity of coronavirus proofreading exoribonuclease.Nature communications · 2025Article
- Ion channel inhibition by targeted recruitment of NEDD4-2 with divalent nanobodies.Nature communications · 2025Article
- Commensal gut bacteria employ de-chelatase HmuS to harvest iron from heme.The EMBO journal · 2025Article
- Oligomeric HIV-1 integrase structures reveal functional plasticity for intasome assembly and RNA binding.Nature communications · 2025Article
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2 authors at 1 institution in 1 country.
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Abstract
Virtually all single-particle cryo-EM experiments currently suffer from specimen adherence to the air-water interface, leading to a non-uniform distribution in the set of projection views. Whereas it is well accepted that uniform projection distributions can lead to high-resolution reconstructions, non-uniform (anisotropic) distributions can negatively affect map quality, elongate structural features, and in some cases, prohibit interpretation altogether. Although some consequences of non-uniform sampling have been described qualitatively, we know little about how sampling quantitatively affects resolution in cryo-EM. Here, we show how inhomogeneity in any projection distribution scheme attenuates the global Fourier Shell Correlation (FSC) in relation to the number of particles and a single geometrical parameter, which we term the sampling compensation factor (SCF). The reciprocal of the SCF is defined as the average over Fourier shells of the reciprocal of the per-particle sampling and normalized to unity for uniform distributions. The SCF therefore ranges from one to zero, with values close to the latter implying large regions of poorly sampled or completely missing data in Fourier space. Using two synthetic test cases, influenza hemagglutinin and human apoferritin, we demonstrate how any amount of sampling inhomogeneity always attenuates the FSC compared to a uniform distribution. We advocate quantitative evaluation of the SCF criterion to approximate the effect of non-uniform sampling on resolution within experimental single-particle cryo-EM reconstructions.
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