One number does not fit all: mapping local variations in resolution in cryo-EM reconstructions

Area of Science:

• Structural biology
• Biophysics
• Computational biology

Background:

• Single particle analysis (SPA) resolution is typically averaged globally.
• Local variations in SPA map resolution are common due to specimen properties or data acquisition.
• Existing methods do not adequately capture these local resolution differences.

Purpose of the Study:

• To introduce a voxel-by-voxel local resolution mapping method for SPA density maps.
• To improve the interpretability of cryo-electron microscopy (cryo-EM) reconstructions.
• To develop an adaptive filtering approach based on local resolution.

Main Methods:

• Utilizing the short-space Fourier transform (SSFT) for local resolution assessment.
• Dividing the experimental volume into small subvolumes for analysis.
• Applying adaptive filtering to reconcile feature resolution with local resolution maps.

Main Results:

• Demonstrated local resolution mapping on both model and experimental cryo-EM data.
• Identified regions with lower-than-average resolution, indicating mobile or heterogeneous components.
• Showcased improved interpretability of density maps through adaptive filtering.

Conclusions:

• Local resolution mapping provides a more accurate assessment of cryo-EM map quality than global averages.
• The SSFT-based approach effectively identifies areas of varying resolution within a map.
• Adaptive filtering based on local resolution enhances the visualization and interpretation of structural features.