Journal
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
Volume 11, Issue 19, Pages 8084-8093Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jpclett.0c02341
Keywords
-
Categories
Funding
- Cassa di Risparmio di Padova e Rovigo (CARIPARO) PROGETTI DI RICERCA SUL COVID-19
Ask authors/readers for more resources
SARS-CoV-2 is a health threat with dire socioeconomical consequences. As the crucial mediator of infection, the viral glycosylated spike protein (S) has attracted the most attention and is at the center of efforts to develop therapeutics and diagnostics. Herein, we use an original decomposition approach to identify energetically uncoupled substructures as antibody binding sites on the fully glycosylated S. Crucially, all that is required are unbiased MD simulations; no prior knowledge of binding properties or ad hoc parameter combinations is needed. Our results are validated by experimentally confirmed structures of S in complex with anti- or nanobodies. We identify poorly coupled subdomains that are poised to host (several) epitopes and potentially involved in large functional conformational transitions. Moreover, we detect two distinct behaviors for glycans: those with stronger energetic coupling are structurally relevant and protect underlying peptidic epitopes, and those with weaker coupling could themselves be prone to antibody recognition.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available