SARS-CoV-2 spike opening dynamics and energetics reveal the individual roles of glycans and their collective impact

Yui Tik Pang, Atanu Acharya, Diane L. Lynch, Anna Pavlova, James C. Gumbart

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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.

Original languageEnglish (US)
Article number1170
JournalCommunications Biology
Volume5
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

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