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- Title
A robust normalized local filter to estimate compositional heterogeneity directly from cryo-EM maps.
- Authors
Forsberg, Björn O.; Shah, Pranav N. M.; Burt, Alister
- Abstract
Cryo electron microscopy (cryo-EM) is used by biological research to visualize biomolecular complexes in 3D, but the heterogeneity of cryo-EM reconstructions is not easily estimated. Current processing paradigms nevertheless exert great effort to reduce flexibility and heterogeneity to improve the quality of the reconstruction. Clustering algorithms are typically employed to identify populations of data with reduced variability, but lack assessment of remaining heterogeneity. Here we develope a fast and simple algorithm based on spatial filtering to estimate the heterogeneity of a reconstruction. In the absence of flexibility, this estimate approximates macromolecular component occupancy. We show that our implementation can derive reasonable input parameters, that composition heterogeneity can be estimated based on contrast loss, and that the reconstruction can be modified accordingly to emulate altered constituent occupancy. This stands to benefit conventionally employed maximum-likelihood classification methods, whereas we here limit considerations to cryo-EM map interpretation, quantification, and particle-image signal subtraction. Heterogeneity in structural biology data includes potentially valuable information about binding and dynamics. Here, the authors devise, validate and demonstrate a method to quantify local heterogeneity in 3D reconstructions.
- Subjects
HETEROGENEITY; SPATIAL filters; ELECTRON microscopy
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-41478-1