Measurement of atom resolvability in cryo-EM maps with Q-scores

Pintilie, Grigore; Zhang, Kaiming; Su, Zhaoming; Li, Shanshan; Schmid, Michael F.; Chiu, Wah

doi:10.1038/s41592-020-0731-1

Title: Measurement of atom resolvability in cryo-EM maps with Q-scores

Journal Article · 10 February 2020 · Nature Methods

DOI: https://doi.org/10.1038/s41592-020-0731-1 · OSTI ID:1604578

^[1];

^[1]; Su, Zhaoming ^[1];

^[1];

^[2];

^[3]

Stanford Univ., CA (United States)
SLAC National Accelerator Lab., Stanford Univ., Menlo Park, CA (United States)
Stanford Univ., CA (United States); SLAC National Accelerator Lab., Stanford Univ., Menlo Park, CA (United States)

Cryogenic electron microscopy (cryo-EM) maps are now at the point where resolvability of individual atoms can be achieved. However, resolvability is not necessarily uniform throughout the map. We introduce a quantitative parameter to characterize the resolvability of individual atoms in cryo-EM maps, the map Q-score. Q-scores can be calculated for atoms in proteins, nucleic acids, water, ligands and other solvent atoms, using models fitted to or derived from cryo-EM maps. Q-scores can also be averaged to represent larger features such as entire residues and nucleotides. Averaged over entire models, Q-scores correlate very well with the estimated resolution of cryo-EM maps for both protein and RNA. Here, assuming the models they are calculated from are well fitted to the map, Q-scores can be used as a measure of resolvability in cryo-EM maps at various scales, from entire macromolecules down to individual atoms. Q-score analysis of multiple cryo-EM maps of the same proteins derived from different laboratories confirms the reproducibility of structural features from side chains down to water and ion atoms.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC); National Inst. of Health

Grant/Contract Number:: AC02-76SF00515; R01GM079429; P41GM103832; S10OD021600

OSTI ID:: 1604578

Journal Information:: Nature Methods, Vol. 17, Issue 3; ISSN 1548-7091

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

Citation Metrics:

Cited by: 133 works

Citation information provided by
Web of Science

References (29)

Molecular dynamics-based refinement and validation for sub-5 Å cryo-electron microscopy maps Singharoy, Abhishek; Teo, Ivan; McGreevy, Ryan eLife, Vol. 5 https://doi.org/10.7554/eLife.16105	journal	July 2016
Guidelines for using Bsoft for high resolution reconstruction and validation of biomolecular structures from electron micrographs: Using Bsoft for Single Particle Reconstruction Heymann, J. Bernard Protein Science, Vol. 27, Issue 1 https://doi.org/10.1002/pro.3293	journal	October 2017
New software tools in EMAN2 inspired by EMDatabank map challenge Bell, James M.; Chen, Muyuan; Durmaz, Tunay Journal of Structural Biology, Vol. 204, Issue 2 https://doi.org/10.1016/j.jsb.2018.09.002	journal	November 2018
Improved metrics for comparing structures of macromolecular assemblies determined by 3D electron-microscopy Joseph, Agnel Praveen; Lagerstedt, Ingvar; Patwardhan, Ardan Journal of Structural Biology, Vol. 199, Issue 1 https://doi.org/10.1016/j.jsb.2017.05.007	journal	July 2017
Refinement of atomic models in high resolution EM reconstructions using Flex-EM and local assessment Joseph, Agnel Praveen; Malhotra, Sony; Burnley, Tom Methods, Vol. 100 https://doi.org/10.1016/j.ymeth.2016.03.007	journal	May 2016
Atomic Dispacement Parameter Nomenclature. Report of a Subcommittee on Atomic Displacement Parameter Nomenclature Trueblood, K. N.; Bürgi, H. B.; Burzlaff, H. Acta Crystallographica Section A Foundations of Crystallography, Vol. 52, Issue 5 https://doi.org/10.1107/S0108767396005697	journal	September 1996
Estimating Electron Density Support for Individual Atoms and Molecular Fragments in X-ray Structures Meyder, Agnes; Nittinger, Eva; Lange, Gudrun Journal of Chemical Information and Modeling, Vol. 57, Issue 10 https://doi.org/10.1021/acs.jcim.7b00391	journal	October 2017
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
Applications of the molecular dynamics flexible fitting method Trabuco, Leonardo G.; Schreiner, Eduard; Gumbart, James Journal of Structural Biology, Vol. 173, Issue 3 https://doi.org/10.1016/j.jsb.2010.09.024	journal	March 2011
EMRinger: side chain–directed model and map validation for 3D cryo-electron microscopy Barad, Benjamin A.; Echols, Nathaniel; Wang, Ray Yu-Ruei Nature Methods, Vol. 12, Issue 10 https://doi.org/10.1038/nmeth.3541	journal	August 2015
Accurate model annotation of a near-atomic resolution cryo-EM map Hryc, Corey F.; Chen, Dong-Hua; Afonine, Pavel V. Proceedings of the National Academy of Sciences, Vol. 114, Issue 12 https://doi.org/10.1073/pnas.1621152114	journal	March 2017
Exploring the gas access routes in a [NiFeSe] hydrogenase using crystals pressurized with krypton and oxygen Zacarias, Sónia; Temporão, Adriana; Carpentier, Philippe JBIC Journal of Biological Inorganic Chemistry, Vol. 25, Issue 6 https://doi.org/10.1007/s00775-020-01814-y	journal	August 2020
Cryo-EM model validation using independent map reconstructions: Cryo-EM Model Validation DiMaio, Frank; Zhang, Junjie; Chiu, Wah Protein Science, Vol. 22, Issue 6 https://doi.org/10.1002/pro.2267	journal	May 2013
Molecular dynamics flexible fitting: A practical guide to combine cryo-electron microscopy and X-ray crystallography Trabuco, Leonardo G.; Villa, Elizabeth; Schreiner, Eduard Methods, Vol. 49, Issue 2 https://doi.org/10.1016/j.ymeth.2009.04.005	journal	October 2009
A fully automatic method yielding initial models from high-resolution cryo-electron microscopy maps Terwilliger, Thomas C.; Adams, Paul D.; Afonine, Pavel V. Nature Methods, Vol. 15, Issue 11 https://doi.org/10.1038/s41592-018-0173-1	journal	October 2018
Refinement of Protein Structures into Low-Resolution Density Maps Using Rosetta DiMaio, Frank; Tyka, Michael D.; Baker, Matthew L. Journal of Molecular Biology, Vol. 392, Issue 1 https://doi.org/10.1016/j.jmb.2009.07.008	journal	September 2009
How large B-factors can be in protein crystal structures Carugo, Oliviero BMC Bioinformatics, Vol. 19, Issue 1 https://doi.org/10.1186/s12859-018-2083-8	journal	February 2018
Water Networks Can Determine the Affinity of Ligand Binding to Proteins Darby, John F.; Hopkins, Adam P.; Shimizu, Seishi Journal of the American Chemical Society, Vol. 141, Issue 40 https://doi.org/10.1021/jacs.9b06275	journal	September 2019
New tools for automated high-resolution cryo-EM structure determination in RELION-3 Zivanov, Jasenko; Nakane, Takanori; Forsberg, Björn O. eLife, Vol. 7 https://doi.org/10.7554/eLife.42166	journal	November 2018
Resolution and Probabilistic Models of Components in CryoEM Maps of Mature P22 Bacteriophage Pintilie, Grigore; Chen, Dong-Hua; Haase-Pettingell, Cameron A. Biophysical Journal, Vol. 110, Issue 4 https://doi.org/10.1016/j.bpj.2015.11.3522	journal	February 2016
MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy Zheng, Shawn Q.; Palovcak, Eugene; Armache, Jean-Paul Nature Methods, Vol. 14, Issue 4 https://doi.org/10.1038/nmeth.4193	journal	February 2017
Real-space refinement in PHENIX for cryo-EM and crystallography Afonine, Pavel V.; Poon, Billy K.; Read, Randy J. Acta Crystallographica Section D Structural Biology, Vol. 74, Issue 6 https://doi.org/10.1107/S2059798318006551	journal	May 2018
UCSF Chimera?A visualization system for exploratory research and analysis Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C. Journal of Computational Chemistry, Vol. 25, Issue 13 https://doi.org/10.1002/jcc.20084	journal	January 2004
Assessment of structural features in Cryo-EM density maps using SSE and side chain Z-scores Pintilie, Grigore; Chiu, Wah Journal of Structural Biology, Vol. 204, Issue 3 https://doi.org/10.1016/j.jsb.2018.08.015	journal	December 2018
Quantifying the local resolution of cryo-EM density maps Kucukelbir, Alp; Sigworth, Fred J.; Tagare, Hemant D. Nature Methods, Vol. 11, Issue 1 https://doi.org/10.1038/nmeth.2727	journal	November 2013
Comparison of Segger and other methods for segmentation and rigid-body docking of molecular components in Cryo-EM density maps Pintilie, Grigore; Chiu, Wah Biopolymers, Vol. 97, Issue 9 https://doi.org/10.1002/bip.22074	journal	June 2012
A beginner's guide to radiation damage Holton, James M. Journal of Synchrotron Radiation, Vol. 16, Issue 2 https://doi.org/10.1107/S0909049509004361	journal	February 2009
Interpretation of atomic displacement parameters from diffraction studies of crystals Dunitz, Jack D.; Schomaker, Verner; Trueblood, Kenneth N. The Journal of Physical Chemistry, Vol. 92, Issue 4 https://doi.org/10.1021/j100315a002	journal	February 1988

Cited By (2)

Cryo-EM structure of a 40 kDa SAM-IV riboswitch RNA at 3.7 Å resolution Zhang, Kaiming; Li, Shanshan; Kappel, Kalli Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-13494-7	journal	December 2019
Structural basis for strand-transfer inhibitor binding to HIV intasomes Passos, Dario Oliveira; Li, Min; Jóźwik, Ilona K. Science, Vol. 367, Issue 6479 https://doi.org/10.1126/science.aay8015	journal	January 2020

Similar Records

Accurate model annotation of a near-atomic resolution cryo-EM map

Journal Article · 2017 · Proceedings of the National Academy of Sciences of the United States of America · OSTI ID:1379782

Hryc, Corey F.; Chen, Dong-Hua; Afonine, Pavel V.; +8 more

Coupling of ssRNA cleavage with DNase activity in type III-A CRISPR-Csm revealed by cryo-EM and biochemistry

Journal Article · 2019 · Cell Research · OSTI ID:1528831

Guo, Minghui; Zhang, Kaiming; Zhu, Yuwei; +7 more

Cryo-EM model validation recommendations based on outcomes of the 2019 EMDataResource challenge

Journal Article · 2021 · Nature Methods · OSTI ID:1777461

Lawson, Catherine L.; Kryshtafovych, Andriy; Adams, Paul D.; +51 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES

Title: Measurement of atom resolvability in cryo-EM maps with Q-scores

Citation Formats

References (29)

Cited By (2)

Similar Records

Related Subjects