SARS-CoV-2 spike opening dynamics and energetics reveal the individual roles of glycans and their collective impact.
Commun Biol
; 5(1): 1170, 2022 Nov 03.
Artículo
en Inglés
| MEDLINE | ID: covidwho-2106509
ABSTRACT
The trimeric spike (S) glycoprotein, which protrudes from the SARS-CoV-2 viral envelope, binds to human ACE2, initiated by at least one protomer's receptor binding domain (RBD) switching from a "down" (closed) to an "up" (open) state. Here, we used large-scale molecular dynamics simulations and two-dimensional replica exchange umbrella sampling calculations with more than a thousand windows and an aggregate total of 160 µs of simulation to investigate this transition with and without glycans. We find that the glycosylated spike has a higher barrier to opening and also energetically favors the down state over the up state. Analysis of the S-protein opening pathway reveals that glycans at N165 and N122 interfere with hydrogen bonds between the RBD and the N-terminal domain in the up state, while glycans at N165 and N343 can stabilize both the down and up states. Finally, we estimate how epitope exposure for several known antibodies changes along the opening path. We find that the BD-368-2 antibody's epitope is continuously exposed, explaining its high efficacy.
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
SARS-CoV-2
/
COVID-19
Tipo de estudio:
Estudio experimental
Límite:
Humanos
Idioma:
Inglés
Revista:
Commun Biol
Año:
2022
Tipo del documento:
Artículo
País de afiliación:
S42003-022-04138-6
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