<i>ISOLDE</i>: a physically realistic environment for model building into low-resolution electron-density maps

Croll, Tristan I.

doi:10.1107/s2059798318002425

Cited by 1,569 publications

(1,214 citation statements)

References 46 publications

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“…The C1 RBD "up" reconstruction was sharpened 160 in cryoSPARC, and the 3D reconstruction with C3 symmetry was subjected to local B-factor 161 sharpening using LocalDeBlur (33). Models were built in Coot, before being iteratively refined 162 in both Phenix and ISOLDE (34)(35)(36). Some of the data processing and refinement software was 163 curated by SBGrid (37).…”

Section: Cryo-em Data Processing 157mentioning

confidence: 99%

Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation

Wrapp

Wang

Corbett

et al. 2020

Preprint

1,351

1,910

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1The outbreak of a novel betacoronavirus (2019-nCov) represents a pandemic threat that has been 2 declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a 3 key target for urgently needed vaccines, therapeutic antibodies, and diagnostics. To facilitate 4 medical countermeasure (MCM) development we determined a 3.5 Å-resolution cryo-EM 5 structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the 6 trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible 7 conformation. We also show biophysical and structural evidence that the 2019-nCoV S binds 8 ACE2 with higher affinity than SARS-CoV S. Additionally we tested several published SARS-9CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 10 nCoV-2019 S, suggesting antibody cross-reactivity may be limited between the two virus RBDs. 11The atomic-resolution structure of 2019-nCoV S should enable rapid development and evaluation

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Section: Cryo-em Data Processing 157mentioning

confidence: 99%

Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation

Wrapp

Wang

Corbett

et al. 2020

Preprint

1,351

1,910

View full text Add to dashboard Cite

show abstract

“…The atomic model was refined against a half-map using Phenix.real_space_refine (Afonine et al, 2018a) and Rosetta . To improve the geometry of the atomic model, molecular dynamics-assisted model building was carried out in ChimeraX (Goddard et al, 2018) using the ISOLDE tool (Croll, 2018). The other half-map was used for generating model statistics.…”

Section: S-protein Ecto Domain Cryo-em Model Buildingmentioning

confidence: 99%

The human coronavirus HCoV-229E S-protein structure and receptor binding

Tomlinson

Wong

et al. 2019

eLife

190

193

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The coronavirus S-protein mediates receptor binding and fusion of the viral and host cell membranes. In HCoV-229E, its receptor binding domain (RBD) shows extensive sequence variation but how S-protein function is maintained is not understood. Reported are the X-ray crystal structures of Class III-V RBDs in complex with human aminopeptidase N (hAPN), as well as the electron cryomicroscopy structure of the 229E S-protein. The structures show that common core interactions define the specificity for hAPN and that the peripheral RBD sequence variation is accommodated by loop plasticity. The results provide insight into immune evasion and the crossspecies transmission of 229E and related coronaviruses. We also find that the 229E S-protein can expose a portion of its helical core to solvent. This is undoubtedly facilitated by hydrophilic subunit interfaces that we show are conserved among coronaviruses. These interfaces likely play a role in the S-protein conformational changes associated with membrane fusion.Li et al. eLife 2019;8:e51230.

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“…Maps of large systems at lower resolutions (~3 Angstroms) from cryoEM can require extensive interactive refinement because more errors are present. The ChimeraX tool ISOLDE 19 , developed by Tristan Croll, enables corrections and makes use of interactive molecular dynamics to maintain correct bonded geometry, minimize clashes, and move atoms into density. It also computes and displays 3D indicators for poor backbone geometry and bond angles.…”

Section: Resultsmentioning

confidence: 99%

Molecular Visualization on the Holodeck

Goddard

Brilliant

Skillman³

et al. 2018

Journal of Molecular Biology

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Can virtual reality be useful for visualizing and analyzing molecular structures and 3-dimensional (3D) microscopy? Uses we are exploring include studies of drug binding to proteins and the effects of mutations, building accurate atomic models in electron microscopy and x-ray density maps, understanding how immune system cells move using 3D light microscopy, and teaching school children about biomolecules that are the machinery of life. What are the advantages and disadvantages of virtual reality for these applications? Virtual reality (VR) offers immersive display with a wide field of view and head tracking for better perception of molecular architectures and uses 6-degree-of-freedom hand controllers for simple manipulation of 3D data. Conventional computer displays with trackpad, mouse and keyboard excel at two-dimensional tasks such as writing and studying research literature, uses for which VR technology is at present far inferior. Adding VR to the conventional computing environment could improve 3D capabilities if new user-interface problems can be solved. We have developed three VR applications: ChimeraX for analyzing molecular structures and electron and light microscopy data, AltPDB for collaborative discussions around atomic models, and Molecular Zoo for teaching young students characteristics of biomolecules. We describe unique aspects of VR user interfaces, and the software and hardware advances needed for this technology to come into routine use for scientific data analysis.

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ISOLDE: a physically realistic environment for model building into low-resolution electron-density maps

Abstract: ISOLDE is an interactive molecular-dynamics environment for rebuilding models against experimental cryo-EM or crystallographic maps. Analysis of its results reinforces the need for great care when validating models built into low-resolution data.

Cited by 1,569 publications

References 46 publications

Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation

Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation

The human coronavirus HCoV-229E S-protein structure and receptor binding

Molecular Visualization on the Holodeck

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