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Computational epitope map of SARS-CoV-2 spike protein
- Source :
- PLoS Computational Biology, Vol 17, Iss 4, p e1008790 (2021), PLoS Computational Biology
- Publication Year :
- 2021
- Publisher :
- Public Library of Science (PLoS), 2021.
-
Abstract
- The primary immunological target of COVID-19 vaccines is the SARS-CoV-2 spike (S) protein. S is exposed on the viral surface and mediates viral entry into the host cell. To identify possible antibody binding sites, we performed multi-microsecond molecular dynamics simulations of a 4.1 million atom system containing a patch of viral membrane with four full-length, fully glycosylated and palmitoylated S proteins. By mapping steric accessibility, structural rigidity, sequence conservation, and generic antibody binding signatures, we recover known epitopes on S and reveal promising epitope candidates for structure-based vaccine design. We find that the extensive and inherently flexible glycan coat shields a surface area larger than expected from static structures, highlighting the importance of structural dynamics. The protective glycan shield and the high flexibility of its hinges give the stalk overall low epitope scores. Our computational epitope-mapping procedure is general and should thus prove useful for other viral envelope proteins whose structures have been characterized.<br />Author summary The SARS-CoV-2 virus has caused a global health crisis. The spike protein exposed at its surface is key for infection and the primary antibody target. However, spike is covered by highly mobile glycan molecules that could impair antibody binding. To identify accessible epitopes, we performed molecular dynamics simulations of an atomistic model of glycosylated spike embedded in a membrane. By combining extensive simulations with bioinformatics analyses, we recovered known antibody binding sites and identified several epitope candidates as targets for further vaccine development.
- Subjects :
- 0301 basic medicine
RNA viruses
Glycosylation
Protein Conformation
Physiology
Coronaviruses
Glycobiology
Molecular Dynamics
01 natural sciences
Biochemistry
Epitope
Virions
Epitopes
Protein structure
Immunogenicity, Vaccine
Computational Chemistry
Immune Physiology
Biochemical Simulations
Medicine and Health Sciences
Macromolecular Structure Analysis
Post-Translational Modification
Biology (General)
Pathology and laboratory medicine
Immune System Proteins
Ecology
biology
Chemistry
Immunogenicity
Medical microbiology
Computational Theory and Mathematics
Modeling and Simulation
Spike Glycoprotein, Coronavirus
Viruses
Physical Sciences
SARS CoV 2
Pathogens
Research Article
Glycan
Protein Structure
COVID-19 Vaccines
SARS coronavirus
QH301-705.5
Immunology
Computational biology
Viral Structure
010402 general chemistry
Microbiology
Antibodies
03 medical and health sciences
Cellular and Molecular Neuroscience
Viral envelope
Viral entry
Virology
Genetics
Molecular Biology
Ecology, Evolution, Behavior and Systematics
Viral vaccines
Organisms
Viral pathogens
COVID-19
Computational Biology
Biology and Life Sciences
Proteins
Viral membrane
0104 chemical sciences
Microbial pathogens
030104 developmental biology
Epitope mapping
biology.protein
Binding Sites, Antibody
Epitope Mapping
Subjects
Details
- Language :
- English
- ISSN :
- 15537358
- Volume :
- 17
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PLoS Computational Biology
- Accession number :
- edsair.doi.dedup.....ac672df4a148ad435b94a891ad686eb9