In 2020, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people worldwide and caused the coronavirus disease 2019 (COVID-19). Spike (S) glycoproteins on the viral membrane bind to ACE2 receptors on the host cell membrane and initiate fusion, and S protein is currently among the primary drug target to inhibit viral entry. The S protein can be in a receptor inaccessible (closed) or accessible (open) state based on down and up positions of its receptor-binding domain (RBD), respectively. However, conformational dynamics and the transition pathway between closed to open states remain unexplored. Here, we performed all-atom molecular dynamics (MD) simulations starting from closed and open states of the S protein trimer in the presence of explicit water and ions. MD simulations showed that RBD forms a higher number of interdomain interactions and exhibits lower mobility in its down position than its up position. MD simulations starting from intermediate conformations between the open and closed states indicated that RBD switches to the up position through a semi-open intermediate that potentially reduces the free energy barrier between the closed and open states. Free energy landscapes were constructed, and a minimum energy pathway connecting the closed and open states was proposed. Because RBD-ACE2 binding is compatible with the semi-open state, but not with the closed state of the S protein, we propose that the formation of the intermediate state is a prerequisite for the host cell recognition.
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21 August 2020
Research Article|
August 18 2020
Conformational transition of SARS-CoV-2 spike glycoprotein between its closed and open states
Mert Gur
;
Mert Gur
a)
1
Department of Mechanical Engineering, Faculty of Mechanical Engineering, Istanbul Technical University (ITU)
, Istanbul, Turkey
2
National Center for High Performance Computing, Istanbul Technical University (ITU)
, Istanbul, Turkey
a)Permanent address: Department of Mechanical Engineering, Istanbul Technical University (ITU), Faculty of Mechanical Engineering, Suite 445 İnönü Caddesi, No. 65 Gümüşsuyu, Beyoğlu, 34437 Istanbul, Turkey. Author to whom correspondence should be addressed: [email protected]. Tel.:Tel.: +90 212 293 13 00. Fax: +90 212 245 07 95. URL: http://gurlab.itu.edu.tr/
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Elhan Taka
;
Elhan Taka
1
Department of Mechanical Engineering, Faculty of Mechanical Engineering, Istanbul Technical University (ITU)
, Istanbul, Turkey
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Sema Zeynep Yilmaz
;
Sema Zeynep Yilmaz
1
Department of Mechanical Engineering, Faculty of Mechanical Engineering, Istanbul Technical University (ITU)
, Istanbul, Turkey
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Ceren Kilinc
;
Ceren Kilinc
1
Department of Mechanical Engineering, Faculty of Mechanical Engineering, Istanbul Technical University (ITU)
, Istanbul, Turkey
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Umut Aktas
;
Umut Aktas
1
Department of Mechanical Engineering, Faculty of Mechanical Engineering, Istanbul Technical University (ITU)
, Istanbul, Turkey
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Mert Golcuk
Mert Golcuk
1
Department of Mechanical Engineering, Faculty of Mechanical Engineering, Istanbul Technical University (ITU)
, Istanbul, Turkey
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Mert Gur
1,2,a)
Elhan Taka
1
Sema Zeynep Yilmaz
1
Ceren Kilinc
1
Umut Aktas
1
Mert Golcuk
1
1
Department of Mechanical Engineering, Faculty of Mechanical Engineering, Istanbul Technical University (ITU)
, Istanbul, Turkey
2
National Center for High Performance Computing, Istanbul Technical University (ITU)
, Istanbul, Turkey
a)Permanent address: Department of Mechanical Engineering, Istanbul Technical University (ITU), Faculty of Mechanical Engineering, Suite 445 İnönü Caddesi, No. 65 Gümüşsuyu, Beyoğlu, 34437 Istanbul, Turkey. Author to whom correspondence should be addressed: [email protected]. Tel.:Tel.: +90 212 293 13 00. Fax: +90 212 245 07 95. URL: http://gurlab.itu.edu.tr/
J. Chem. Phys. 153, 075101 (2020)
Article history
Received:
April 17 2020
Accepted:
July 19 2020
Citation
Mert Gur, Elhan Taka, Sema Zeynep Yilmaz, Ceren Kilinc, Umut Aktas, Mert Golcuk; Conformational transition of SARS-CoV-2 spike glycoprotein between its closed and open states. J. Chem. Phys. 21 August 2020; 153 (7): 075101. https://doi.org/10.1063/5.0011141
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