New tools for the analysis and validation of cryo-EM maps and atomic models

Afonine, Pavel V.; Klaholz, Bruno P.; Moriarty, Nigel W.; Poon, Billy K.; Sobolev, Oleg V.; Terwilliger, Thomas C.; Adams, Paul D.; Urzhumtsev, Alexandre

doi:10.1107/s2059798318009324

Cited by 684 publications

(482 citation statements)

References 106 publications

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“…Typically, maps in this resolution range contain enough information to reliably trace the backbone and some of the side chains. However, in practice even models built on such well‐resolved maps are not void of structural inconsistencies or errors …”

Section: Resultsmentioning

confidence: 99%

“…For assessing the goodness‐of‐fit, we used three software packages: PHENIX, TEMPy, and EMRinger . The overall model‐to‐map goodness‐of‐fit is quantified using PHENIX's real space correlation coefficients— CC volume , CC mask , and CC peaks ,—each probing different aspects of model‐to‐map fit; TEMPY's cross‐correlation coefficients— CCC , CCC ov , the Laplacian‐filtered correlation coefficient—LAP and the average per‐chain Segment‐based Mander's Overlap Coefficients— SMOC f and SMOC d ; and EMRinger's global score enumerating accuracy of side‐chain placement within map density …”

Section: Methodsmentioning

confidence: 99%

“…The per‐residue (local) model‐to‐map goodness‐of‐fit is evaluated with PHENIX's local CC box measure; local EMRinger score; and TEMPy's local SMOC f and SMOC d scores . SMOC f is calculated on overlapping residue windows (sequence fragments), whereas SMOC d on the voxels occupied by the atoms of a specific residue.…”

Section: Methodsmentioning

confidence: 99%

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Cryo‐electron microscopy targets in CASP13: Overview and evaluation of results

et al. 2019

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Structures of seven CASP13 targets were determined using cryo‐electron microscopy (cryo‐EM) technique with resolution between 3.0 and 4.0 Å. We provide an overview of the experimentally derived structures and describe results of the numerical evaluation of the submitted models. The evaluation is carried out by comparing coordinates of models to those of reference structures (CASP‐style evaluation), as well as checking goodness‐of‐fit of modeled structures to the cryo‐EM density maps. The performance of contributing research groups in the CASP‐style evaluation is measured in terms of backbone accuracy, all‐atom local geometry and similarity of inter‐subunit interfaces. The results on the cryo‐EM targets are compared with those on the whole set of eighty CASP13 targets. A posteriori refinement of the best models in their corresponding cryo‐EM density maps resulted in structures that are very close to the reference structure, including some regions with better fit to the density.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Cryo‐electron microscopy targets in CASP13: Overview and evaluation of results

et al. 2019

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“…Cryo-EM specific tools have recently been added, ranging from map analysis and improvement (phenix.mtriage (Afonine et al, 2018b); phenix.auto_sharpen (Terwilliger et al, 2018)) to model validation and real-space model optimization (phenix.real_space_refine (Afonine et al, 2013; Afonine et al, 2018a)). For single-model analysis, we used the PHENIX model validation tools to quantify deviations of five geometric parameters - bond distances, angles, chirality, planarity and dihedral angles - from ideal values (Vagin et al, 2004).…”

Section: Evaluation Measuresmentioning

confidence: 99%

“…Higher box_CC values usually signify a better fit to map. Low values do not necessarily mean that the model does not fit the map well, but may instead indicate that there are uninterpreted map regions or poorly connecting densities (Afonine et al, 2018b). Overall FSC is calculated between the complex-valued Fourier map and model coefficients binned in resolution shells.…”

Section: Evaluation Measuresmentioning

confidence: 99%

Evaluation system and web infrastructure for the second cryo-EM model challenge

Kryshtafovych

Adams

Lawson

et al. 2018

Journal of Structural Biology

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An evaluation system and a web infrastructure were developed for the second cryo-EM model challenge. The evaluation system includes tools to validate stereo-chemical plausibility of submitted models, check their fit to the corresponding density maps, estimate their overall and per-residue accuracy, and assess their similarity to reference cryo-EM or X-ray structures as well as other models submitted in this challenge. The web infrastructure provides a convenient interface for analyzing models at different levels of detail. It includes interactively sortable tables of evaluation scores for different subsets of models and different sublevels of structure organization, and a suite of visualization tools facilitating model analysis. The results are publicly accessible at http://model-compare.emdatabank.org.

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Cryo‐Electron Microscopy in Drug Discovery and Development: Opportunities and Challenges

Gomez‐Llorente

Hong

Scapin

2021

Burger's Medicinal Chemistry and Drug Discovery

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While utilization of structural information has been a staple technology in drug discovery for many years, electron microscopy creates opportunities that have been thus far out of reach for the conventional techniques, like the visualization of very large molecular complexes in solution or obtaining high‐resolution structural data for small molecules from microcrystals. These opportunities come at a cost: hardware is extremely expensive, software is ever‐changing, and constantly challenged by new developments in the hardware and requests by the users, and IT departments are faced with significant requirements for storage and computational power. Nevertheless, the establishment of centralized facilities, commercial consortia, and cooperative research centers is well positioned to provide access to Cryo‐EM to an expanded base of researchers, from academia as well as from industry. Understanding of the requirements, advantages, and limitations of this technique becomes then necessary to ensure correct decision‐making processes and resource allocation when undertaking a structure‐guided drug design project.

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New tools for the analysis and validation of cryo-EM maps and atomic models

Abstract: New methods and PHENIX tools for quality assessment of cryo-EM maps, atomic models and model-to-map fitting are presented. Results of systematic application of these tools to high-resolution cryo-EM maps and corresponding atomic models are analyzed and discussed.

Cited by 684 publications

References 106 publications

Cryo‐electron microscopy targets in CASP13: Overview and evaluation of results

Cryo‐electron microscopy targets in CASP13: Overview and evaluation of results

Evaluation system and web infrastructure for the second cryo-EM model challenge

Cryo‐Electron Microscopy in Drug Discovery and Development: Opportunities and Challenges

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