PropertyValue
?:abstract
  • A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) has emerged as a human pathogen, causing global pandemic and resulting in over 400,000 deaths worldwide. The surface spike protein of SARS-CoV-2 mediates the process of coronavirus entry into human cells by binding angiotensin-converting enzyme 2 (ACE2). Due to the critical role in viral-host interaction and the exposure of spike protein, it has been a focus of most vaccines’ developments. However, the structural and biochemical studies of the spike protein are challenging because it is thermodynamically metastable1. Here, we develop a new pipeline that automatically identifies mutants that thermodynamically stabilize the spike protein. Our pipeline integrates bioinformatics analysis of conserved residues, motion dynamics from molecular dynamics simulations, and other structural analysis to identify residues that significantly contribute to the thermodynamic stability of the spike protein. We then utilize our previously developed protein design tool, Eris, to predict thermodynamically stabilizing mutations in proteins. We validate the ability of our pipeline to identify protein stabilization mutants through known prefusion spike protein mutants. We finally utilize the pipeline to identify new prefusion spike protein stabilization mutants.
?:creator
?:doi
?:doi
  • 10.1101/2020.06.17.157081
?:externalLink
?:journal
  • bioRxiv
?:license
  • biorxiv
?:pdf_json_files
  • document_parses/pdf_json/88feff932fe1dde23435a79a296c16cda0d6880f.json
?:publication_isRelatedTo_Disease
?:sha_id
?:source
  • BioRxiv
?:title
  • Prefusion spike protein stabilization through computational mutagenesis
?:type
?:year
  • 2020-06-19

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