Open AccessImprovement of cryo-EM maps by density modification
Author(s) -
Thomas C. Terwilliger,
Steven J. Ludtke,
Randy J. Read,
Paul D. Adams,
Pavel V. Afonine
Publication year - 2020
Publication title -
nature methods
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 19.469
H-Index - 318
eISSN - 1548-7105
pISSN - 1548-7091
DOI - 10.1038/s41592-020-0914-9
Subject(s) - cryo electron microscopy , basis (linear algebra) , sequence (biology) , visibility , biological system , set (abstract data type) , materials science , algorithm , computer science , physics , chemistry , mathematics , optics , biology , nuclear magnetic resonance , biochemistry , geometry , programming language
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.