U.S. Department of EnergyOffice of Scientific and Technical Information
The SARS-CoV-2 Spike Variant D614G Favors an Open Conformational State
Abstract
The COVID-19 pandemic underwent a rapid transition with the emergence of a dominant viral variant (from the “D-form” to the “G-form”) that carried an amino acid substitution D614G in its “Spike” protein. The G-form is more infectious in vitro and associated with increased viral loads. To gain insight into the molecular-level underpinnings of these characteristics, we employed microsecond all-atom simulations. Here we show that changes in the protein energetics favor a higher population of infection-capable (open) states through release of hydrogen bonds of an asymmetry present in the D-form but not the G-form. Thus, the increased infectivity of the G-form is likely due to a higher rate of profitable binding encounters with the host receptor. It is also predicted to be more neutralization sensitive due to enhanced exposure of the receptor binding domain, a key target region for neutralizing antibodies. These results are significant for vaccine design. The Molecular Dynamics Simulations datasets generated in this study, namely that of the soluble form SARS-CoV-2 Spike protein are made available here. Details of the trajectory and supporting files are given in the README.txt file.
- Authors:
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- Concordia University, Montreal, Quebec, Canada; Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Los Alamos National Laboratory
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- Duke Human Vaccine Institute & Department of Surgery
- Publication Date:
- Other Number(s):
- LA-UR-21-20410
- DOE Contract Number:
- 89233218CNA000001
- Research Org.:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- USDOE Laboratory Directed Research and Development (LDRD) Program
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; 97 MATHEMATICS AND COMPUTING; COVID19; SARS-COV-2; biomolecular modeling; coronavirus; immunogen design; molecular dynamics simulations
- OSTI Identifier:
- 1760388
- DOI:
- https://doi.org/10.25583/1760388
Citation Formats
Mansbach, Rachael, Chakraborty, Srirupa, Nguyen, Kien, Montefiori, David, Korber, Bette, and Gnanakaran, Sandrasegaram. The SARS-CoV-2 Spike Variant D614G Favors an Open Conformational State. United States: N. p., 2021.
Web. doi:10.25583/1760388.
Mansbach, Rachael, Chakraborty, Srirupa, Nguyen, Kien, Montefiori, David, Korber, Bette, & Gnanakaran, Sandrasegaram. The SARS-CoV-2 Spike Variant D614G Favors an Open Conformational State. United States. doi:https://doi.org/10.25583/1760388
Mansbach, Rachael, Chakraborty, Srirupa, Nguyen, Kien, Montefiori, David, Korber, Bette, and Gnanakaran, Sandrasegaram. 2021.
"The SARS-CoV-2 Spike Variant D614G Favors an Open Conformational State". United States. doi:https://doi.org/10.25583/1760388. https://www.osti.gov/servlets/purl/1760388. Pub date:Tue Jan 19 04:00:00 UTC 2021
@article{osti_1760388,
title = {The SARS-CoV-2 Spike Variant D614G Favors an Open Conformational State},
author = {Mansbach, Rachael and Chakraborty, Srirupa and Nguyen, Kien and Montefiori, David and Korber, Bette and Gnanakaran, Sandrasegaram},
abstractNote = {The COVID-19 pandemic underwent a rapid transition with the emergence of a dominant viral variant (from the “D-form” to the “G-form”) that carried an amino acid substitution D614G in its “Spike” protein. The G-form is more infectious in vitro and associated with increased viral loads. To gain insight into the molecular-level underpinnings of these characteristics, we employed microsecond all-atom simulations. Here we show that changes in the protein energetics favor a higher population of infection-capable (open) states through release of hydrogen bonds of an asymmetry present in the D-form but not the G-form. Thus, the increased infectivity of the G-form is likely due to a higher rate of profitable binding encounters with the host receptor. It is also predicted to be more neutralization sensitive due to enhanced exposure of the receptor binding domain, a key target region for neutralizing antibodies. These results are significant for vaccine design. The Molecular Dynamics Simulations datasets generated in this study, namely that of the soluble form SARS-CoV-2 Spike protein are made available here. Details of the trajectory and supporting files are given in the README.txt file.},
doi = {10.25583/1760388},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Tue Jan 19 04:00:00 UTC 2021},
month = {Tue Jan 19 04:00:00 UTC 2021}
}