Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Modeling SARS-CoV-2 proteins in the CASP-commons experiment.

ABSTRACT: Critical Assessment of Structure Prediction (CASP) is an organization aimed at advancing the state of the art in computing protein structure from sequence. In the spring of 2020, CASP launched a community project to compute the structures of the most structurally challenging proteins coded for in the SARS-CoV-2 genome. Forty-seven research groups submitted over 3000 three-dimensional models and 700 sets of accuracy estimates on 10 proteins. The resulting models were released to the public. CASP community members also worked together to provide estimates of local and global accuracy and identify structure-based domain boundaries for some proteins. Subsequently, two of these structures (ORF3a and ORF8) have been solved experimentally, allowing assessment of both model quality and the accuracy estimates. Models from the AlphaFold2 group were found to have good agreement with the experimental structures, with main chain GDT_TS accuracy scores ranging from 63 (a correct topology) to 87 (competitive with experiment).

SUBMITTER: Kryshtafovych A

PROVIDER: S-EPMC8616790 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Prediction of homoprotein and heteroprotein complexes by protein docking and template-based modeling: A CASP-CAPRI experiment.

Project description:We present the results for CAPRI Round 30, the first joint CASP-CAPRI experiment, which brought together experts from the protein structure prediction and protein-protein docking communities. The Round comprised 25 targets from amongst those submitted for the CASP11 prediction experiment of 2014. The targets included mostly homodimers, a few homotetramers, and two heterodimers, and comprised protein chains that could readily be modeled using templates from the Protein Data Bank. On average 24 CAPRI groups and 7 CASP groups submitted docking predictions for each target, and 12 CAPRI groups per target participated in the CAPRI scoring experiment. In total more than 9500 models were assessed against the 3D structures of the corresponding target complexes. Results show that the prediction of homodimer assemblies by homology modeling techniques and docking calculations is quite successful for targets featuring large enough subunit interfaces to represent stable associations. Targets with ambiguous or inaccurate oligomeric state assignments, often featuring crystal contact-sized interfaces, represented a confounding factor. For those, a much poorer prediction performance was achieved, while nonetheless often providing helpful clues on the correct oligomeric state of the protein. The prediction performance was very poor for genuine tetrameric targets, where the inaccuracy of the homology-built subunit models and the smaller pair-wise interfaces severely limited the ability to derive the correct assembly mode. Our analysis also shows that docking procedures tend to perform better than standard homology modeling techniques and that highly accurate models of the protein components are not always required to identify their association modes with acceptable accuracy. Proteins 2016; 84(Suppl 1):323-348. © 2016 Wiley Periodicals, Inc.

| S-EPMC5030136 | biostudies-literature

Understanding the general packing rearrangements required for successful template based modeling of protein structure from a CASP experiment.

Project description:As an alternative to the common template based protein structure prediction methods based on main-chain position, a novel side-chain centric approach has been developed. Together with a Bayesian loop modeling procedure and a combination scoring function, the Stone Soup algorithm was applied to the CASP9 set of template based modeling targets. Although the method did not generate as large of perturbations to the template structures as necessary, the analysis of the results gives unique insights into the differences in packing between the target structures and their templates. Considerable variation in packing is found between target and template structures even when the structures are close, and this variation is found due to 2 and 3 body packing interactions. Outside the inherent restrictions in packing representation of the PDB, the first steps in correctly defining those regions of variable packing have been mapped primarily to local interactions, as the packing at the secondary and tertiary structure are largely conserved. Of the scoring functions used, a loop scoring function based on water structure exhibited some promise for discrimination. These results present a clear structural path for further development of a side-chain centered approach to template based modeling.

| S-EPMC3867305 | biostudies-literature

Opposing activities of IFITM proteins in SARS-CoV-2 infection

Project description:Interferon-induced transmembrane proteins (IFITMs) restrict infections by many viruses, but a subset of IFITMs enhance infections by specific coronaviruses through currently unknown mechanisms. We show that SARS-CoV-2 Spike-pseudotyped virus and genuine SARS-CoV-2 infections are generally restricted by human and mouse IFITM1, IFITM2, and IFITM3, using gain- and loss-of-function approaches. Mechanistically, SARS-CoV-2 restriction occurred independently of IFITM3 S-palmitoylation, indicating a restrictive capacity distinct from reported inhibition of other viruses. In contrast, the IFITM3 amphipathic helix and its amphipathic properties were required for virus restriction. Mutation of residues within the IFITM3 endocytosis-promoting Yxx? motif converted human IFITM3 into an enhancer of SARS-CoV-2 infection, and cell-to-cell fusion assays confirmed the ability of endocytic mutants to enhance Spike-mediated fusion with the plasma membrane. Overexpression of TMPRSS2, which increases plasma membrane fusion versus endosome fusion of SARS-CoV-2, attenuated IFITM3 restriction and converted amphipathic helix mutants into infection enhancers. In sum, we uncover new pro- and anti-viral mechanisms of IFITM3, with clear distinctions drawn between enhancement of viral infection at the plasma membrane and amphipathicity-based mechanisms used for endosomal SARS-CoV-2 restriction.

| S-SCDT-EMBOJ-2020-106501 | biostudies-other

Structures from "Engineering Neutralizing SARS-CoV Antibodies to Bind SARS-CoV-2"

Project description: Not available

| S-BSST379 | biostudies-other

Cryo-EM structure of SARS-CoV-2 Spike Proteins on intact virions

Project description: Not available

| EMPIAR-10492 | biostudies-other

RNA sequencing of SARS-CoV and SARS-CoV-2 N proteins expressing cell lines

Project description:SARS-CoV and SARS-CoV-2, the causative agents of severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19), are genetically related positive-sense RNA viruses that may cause similar pathophysiology. Despite host could activate interferon responses upon coronaviral infection to suppress virus replication, both SARS-CoV and SARS-CoV-2 have evolved strategies to inhibit interferon response. Here, we constructed SARS-CoV and SARS-CoV-2 N proteins expressing cell lines (HEK293T-N and HEK293T-2N) and performed RNA sequencing analysis, showing that both SARS-CoV-2 and SARS-CoV N proteins could inhibit expression of early growth response gene 1 (EGR1) to suppress interferon response. Moreover, EGR1 could degrade N proteins of SARS-CoV and SARS-CoV-2 in a lysosome-dependent manner, and inhibit viral replication of SARS-CoV-2. Our findings revealed the important role of EGR1 in host innate immune response against SARS-CoV and SARS-CoV-2, which would contribute to understanding the pathogenesis of human coronaviruses and development of antiviral therapies. In addition, we demonstrated that both N proteins could upregulate expression of nervous development-related genes, which may be associated with the neurological symptoms of COVID-19 and SARS patients.

2023-08-20 | GSE189706 | GEO

Subtomogram averaging and classification of SARS-CoV-2 Spike Proteins on intact virions

Project description: Not available

| EMPIAR-10493 | biostudies-other

Target highlights from the first post-PSI CASP experiment (CASP12, May-August 2016).

Project description:The functional and biological significance of the selected CASP12 targets are described by the authors of the structures. The crystallographers discuss the most interesting structural features of the target proteins and assess whether these features were correctly reproduced in the predictions submitted to the CASP12 experiment.

| S-EPMC5820184 | biostudies-literature

Control of complement-induced inflammatory responses to SARS-CoV-2 infection by anti-SARS-CoV-2 antibodies

Project description:Dysregulated immune responses contribute to the excessive and uncontrolled inflammation observed in severe COVID-19. However, how immunity to SARS-CoV-2 is induced and regulated remains unclear. Here we uncover a role of the complement system in the induction of innate and adaptive immunity to SARS-CoV-2. Complement rapidly opsonizes SARS-CoV-2 particles via the lectin pathway. Complement-opsonized SARS-CoV-2 efficiently induces type-I interferon and pro-inflammatory cytokine responses via activation of dendritic cells, which are inhibited by antibodies against the complement receptors (CR) 3 and 4. Serum from COVID-19 patients, or monoclonal antibodies against SARS-CoV-2, attenuate innate and adaptive immunity induced by complement-opsonized SARS-CoV-2. Blocking of CD32, the FcγRII antibody receptor of dendritic cells, restores complement-induced immunity. These results suggest that opsonization of SARS-CoV-2 by complement is involved in the induction of innate and adaptive immunity to SARS-CoV-2 in the acute phase of infection. Subsequent antibody responses limit inflammation and restore immune homeostasis. These findings suggest that dysregulation of the complement system and FcγRII signaling may contribute to severe COVID-19.

| S-SCDT-10_1038-S44318-024-00061-0 | biostudies-other

Modeling the binding of protoporphyrin IX, verteporfin, and chlorin e6 to SARS-CoV-2 proteins.

Project description:In this work, we analyze the latest data on the molecular docking of a range of SARS-CoV-2 proteins to protoporphyrin IX, verteporfin, and chlorin e6, as well as consider the prospects for using chlorins and porphyrins as agents for photoinactivation of the SARS2 virus.

| S-EPMC8118678 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data