Journal Article

Improvement of cryo-EM maps by density modification

Read, Randy J., Adams, Paul D., Ludtke, Steven J., Afonine, Pavel V., Terwilliger, Thomas C.

2020

Overview

A density-modification procedure for improving maps from single-particle electron cryogenic microscopy (cryo-EM) is presented. The theoretical basis of the method is identical to that of maximum-likelihood density modification, previously used to improve maps from macromolecular X-ray crystallography. Key differences from applications in crystallography are that the errors in Fourier coefficients are largely in the phases in crystallography but in both phases and amplitudes in cryo-EM, and that half-maps with independent errors are available in cryo-EM. These differences lead to a distinct approach for combination of information from starting maps with information obtained in the density-modification process. The density-modification procedure was applied to a set of 104 datasets and improved map-model correlation and increased the visibility of details in many of the maps. The procedure requires two unmasked half-maps and a sequence file or other source of information on the volume of the macromolecule that has been imaged. A method based on maximum likelihood density modification, adapted from X-ray crystallography, improves cryo-EM maps.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/1647/2258/1258/1259 / 631/1647/794 / Analysis / Apoferritins - chemistry / Bioinformatics / Biological Microscopy / Biological Techniques / Biomedical and Life Sciences / Biomedical Engineering/Biotechnology / cryoelectron microscopy / Cryoelectron Microscopy - methods / Crystallography / Density / Image Processing, Computer-Assisted / Life Sciences / Macromolecules / OTHER INSTRUMENTATION / Protein Conformation / Proteomics / Software / Specific gravity / Visibility / X-ray crystallography