Computational epitope map of SARS-CoV-2 spike protein

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 s...

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Bibliographic Details
Published in:PLoS computational biology 2021-04, Vol.17 (4), p.e1008790-e1008790
Main Authors: Sikora, Mateusz, von Bülow, Sören, Blanc, Florian E C, Gecht, Michael, Covino, Roberto, Hummer, Gerhard
Format: Article
Language:English
Subjects:
Accessibility
Antibodies
Antigenic determinants
Binding sites
Binding Sites, Antibody
Biology and Life Sciences
Computational Biology
Computer applications
Coronaviruses
COVID-19
COVID-19 - virology
COVID-19 Vaccines - immunology
Docking
Epitope Mapping - methods
Epitopes
Epitopes - chemistry
Epitopes - immunology
Fab
Glycan
Immunogenicity, Vaccine
Lower bounds
Medicine and Health Sciences
Pandemics
Physical Sciences
Physiological aspects
Polysaccharides
Protein Conformation
Proteins
Rigidity
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Simulation
Spike Glycoprotein, Coronavirus - chemistry
Spike Glycoprotein, Coronavirus - immunology
Spike protein
Structural models
Upper bounds
Vaccines
Viral proteins
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Summary: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.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1008790