Improvement of Cryo-Em Maps by Density Modification

Authors

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

Publication Date

9-1-2020

Journal

Nature Methods

DOI

10.1038/s41592-020-0914-9

PMID

32807957

PMCID

PMC7484085

PubMedCentral® Posted Date

2-17-2021

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Apoferritins, Cryoelectron Microscopy, Image Processing, Computer-Assisted, Protein Conformation, Software

Abstract

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.