All-atom simulations of the trimeric spike protein of SARS-CoV-2 in aqueous medium: Nature of interactions, conformational stability and free energy diagrams for conformational transition of the protein.
closed and open conformational states
direct and water-bridged hydrogen bonds
free energy diagram
intra- and inter-chain interactions
spike protein of SARS-COV-2
Journal
Journal of computational chemistry
ISSN: 1096-987X
Titre abrégé: J Comput Chem
Pays: United States
ID NLM: 9878362
Informations de publication
Date de publication:
30 06 2023
30 06 2023
Historique:
revised:
02
03
2023
received:
21
12
2022
accepted:
08
03
2023
medline:
22
5
2023
pubmed:
1
4
2023
entrez:
31
3
2023
Statut:
ppublish
Résumé
The spike protein of SARS-CoV-2 exists in two major conformational states, namely the 'open' and 'closed' states which are also known as the 'up' and 'down' states, respectively. In its open state, the receptor binding domain (RBD) of the protein is exposed for binding with ACE2, whereas the spike RBD is inaccessible to ACE2 in the closed state of the protein. In the current work, we have performed all-atom microsecond simulations of the full-length trimeric spike protein solvated in explicit aqueous medium with an average system size of ~0.7 million atoms to understand the molecular nature of intra- and inter-chain interactions, water-bridged interactions between different residues that contribute to the stability of the open and closed states of the protein, and also the free energy landscape for transition between the open and closed states of the protein. We have also examined the changes of such interactions that are associated with switching from one state to the other through both unbiased and biased simulations at all-atom level with total run length of 4 μs. Interestingly, after about 0.8 μs of unbiased molecular dynamics run of the spike system in the open state, we observed a gradual transition of the monomeric chain (B) from open to its partially closed or down state. Initially the residues at the interface of chain B RBD in the open state spike protein were at non-hydrogen-bonding distances from the residues of chain C RBD. However, the two RBDs gradually came closer and finally the residue S459 of the RBD of chain B made a hydrogen bond with F374 of chain C in the last 200 ns of the simulation along with formation of a few more hydrogen bonds involving other residues. Since no transition from closed to the open state of the protein is observed in the present 1 μs unbiased simulation of the closed state protein, the current study seems to suggest that the closed conformational state is preferred for the spike protein of SARS-CoV-2 in aqueous medium. Furthermore, calculations of the free energy surface of the conformational transition from open (up) to the closed (down) state using a biased simulation method reveal a free energy barrier of ~3.20 kcal/mol for the transition of RBD from open to the closed state, whereas the barrier for the reverse process is found to be significantly higher.
Substances chimiques
spike protein, SARS-CoV-2
0
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Spike Glycoprotein, Coronavirus
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1560-1577Informations de copyright
© 2023 Wiley Periodicals LLC.
Références
B. J. Bosch, R. van der Zee, C. A. M. de Haan, P. J. M. Rottier, J. Virol. 2003, 77, 8801.
S. K. M. Haque, O. Ashwaq, A. Sarief, A. K. A. J. Mohamed, Future Virol. 2020, 15, 625.
J. Lan, J. Ge, J. Yu, S. Shan, H. Zhou, S. Fan, Q. Zhang, X. Shi, Q. Wang, L. Zhang, Nature 2020, 581, 215.
M. Letko, A. Marzi, V. Munster, Microbiology 2020, 5, 562.
W. Li, M. J. Moore, N. Vasilieva, J. Sui, S. K. Wong, M. A. Berne, M. Somasundaran, J. L. Sullivan, K. Luzuriaga, T. C. Greenough, H. Choe, M. Farzan, Nature 2003, 426, 450.
B. Coutard, C. Valle, X. de Lamballerie, B. Canard, N. G. Seidah, E. De-croly, Antiviral Res. 2020, 176, 104742.
S. Belouzard, J. K. Millet, B. N. Licitra, G. R. Whittaker, Viruses 2012, 4, 1011.
T. M. Gallagher, M. J. Buchmeier, Virology 2001, 279, 371.
C. Zhu, G. He, Q. Yin, L. Zeng, X. Ye, Y. Shi, W. Xu, J. Med. Virol. 2021, 93, 5729.
R. Henderson, R. J. Edwards, K. Mansouri, K. Janowska, V. Stalls, S. M. C. Gobeil, M. Kopp, D. Li, R. Parks, A. L. Hsu, M. J. Borgnia, B. F. Haynes, P. Acharya, Nat. Struct. Mol. Biol. 2020, 27, 925.
A. Sternberg, C. Naujokat, Life Sci. 2020, 257, 118056.
S. K. Samrat, A. M. Tharappel, Z. Li, H. Li, Virus Res. 2020, 288, 198141.
R. N. Kirchdoerfer, N. Wang, J. Pallesen, D. Wrapp, H. L. Turner, C. A. Cottrell, K. S. Corbett, B. S. Graham, J. S. McLellan, A. B. Ward, Sci. Rep. 2018, 8, 1.
J. E. Park, K. Li, A. Barlan, A. R. Fehr, S. Perlman, P. B. McCray, T. Gallagher, Proc. Natl. Acad. Sci. U. S. A. 2016, 113, 12262.
Y. Han, H. Yang, J. Med. Virol. 2020, 92, 639.
F. Wu, S. Zhao, B. Yu, Y. M. Chen, W. Wang, Z. G. Song, Y. Hu, Z. W. Tao, J. H. Tian, Y. Y. Pei, M. L. Yuan, Y. L. Zhang, F. H. Dai, Y. Liu, Q. M. Wang, J. J. Zheng, L. Xu, E. C. Holmes, Y. Z. Zhang, Nature 2020, 579, 265.
Y. Koichi, F. Miho, K. Sophia, Clin. Immunol. 2020, 215, 108427.
J. S. Tregoning, E. S. Brown, H. M. Cheeseman, K. E. Flight, S. L. Higham, N. M. Lemm, B. F. Pierce, D. C. Stirling, Z. Wang, K. M. Pollock, Clin. Exp. Immunol. 2020, 202, 162.
D. Wrapp, N. Wang, K. S. Corbett, J. A. Goldsmith, C. L. Hsieh, O. Abiona, B. S. Graham, J. S. McLellan, Science 2020, 367, 1260.
M. Gur, E. Taka, S. Z. Yilmaz, C. Kilinc, U. Aktas, M. Golcuk, J. Chem. Phys. 2020, 153, 75101.
R. Ray, L. Le, I. Andricioaei, Proc. Natl. Acad. Sci. 2021, 118, e2100943118.
A. K. Padhi, S. L. Rath, T. Tripathi, J. Phys. Chem. B 2021, 125, 9078.
P. R. Arantes, A. Saha, G. Palermo, ACS Cent. Sci. 2020, 6, 1654.
S. Roy, A. Jaiswar, R. Sarkar, J. Phys. Chem. Lett. 2020, 11, 7021.
A. Yu, A. J. Pak, P. He, V. Monje-Galvan, L. Casalino, Z. Gaieb, A. C. Dommer, R. E. Amaro, G. A. A. Voth, Biophys. J. 2021, 120, 1097.
R. A. Romer, N. S. Romer, A. K. Wallis, Sci. Rep. 2021, 11, 4257.
J. K. Williams, B. Wang, A. Sam, C. L. Hoop, D. A. Case, J. Baum, Proteins 2022, 90, 1044.
T. Mori, J. Jung, C. Kobayashi, H. M. Dokainish, S. Re, Y. Sugita, Biophys. J. 2021, 120, 1060.
L. Casalino, Z. Gaieb, J. A. Goldsmith, C. K. Hjorth, A. C. Dommer, A. M. Harbison, C. A. Fogarty, E. P. Barros, B. C. Taylor, J. S. McLellan, E. Fadda, R. E. Amaro, ACS Cent. Sci. 2020, 6, 1722.
H. Woo, S.-J. Park, Y. K. Choi, T. Park, M. Tanveer, Y. Cao, N. R. Kern, J. Lee, M. S. Yeom, T. I. Croll, C. Seok, W. Im, J. Phys. Chem. B 2020, 124, 7128.
Y. K. Choi, Y. Cao, M. Frank, H. Woo, S.-J. Park, M. S. Yeom, T. I. Croll, C. Seok, W. Im, J. Chem. Theory Comput. 2021, 17, 2479.
T. Leong, C. Voleti, Z. Peng, Front. Phys. 2021, 9, 680983.
A. Ali, R. Vijayan, Sci. Rep. 2020, 10, 14214.
Y. Wang, M. Liu, J. Gao, Proc. Natl. Acad. Sci. U. S. A. 2020, 117, 13967.
C. Peng, Z. Zhu, Y. Shi, X. Wang, K. Mu, Y. Yang, X. Zhang, Z. Xu, W. Zhu, J. Phys. Chem. Lett. 2020, 11, 10482.
J. Zou, J. Yin, L. Fang, M. Yang, T. Wang, W. Wu, M. A. Bellucci, P. Zhang, J. Chem. Inf. Model. 2020, 60, 5794.
G. Mariano, R. J. Farthing, S. L. M. Lale-Farjat, J. R. C. Bergeron, Front. Mol. Biosci. 2020, 7, 344.
P. M. Mishra, C. K. Nandi, J. Phys. Chem. B 2021, 125, 8395.
E. Laurini, D. Marson, S. Aulic, A. Fermeglia, S. Pricl, ACS Nano 2021, 15, 6929.
E. Laurini, D. Marson, S. Aulic, M. Fermeglia, S. Pricl, ACS Nano 2020, 14, 11821.
A. Spinello, A. Saltalamacchia, A. Magistrato, J. Phys. Chem. Lett. 2020, 11, 4785.
M. Amin, M. K. Sorour, A. Kasry, J. Phys. Chem. Lett. 2020, 11, 4897.
H. L. Nguyen, P. D. Lan, N. Q. Thai, D. A. Nissley, E. P. O'Brien, M. S. Li, J. Phys. Chem. B 2020, 124, 7336.
S. Kim, Y. Liu, Z. Lei, J. Dicker, Y. Cao, X. F. Zhang, W. Im, J. Chem. Theory Comput. 2021, 17, 7972.
S. Pascarella, M. Ciccozzi, D. Zella, M. Bianchi, F. Benedetti, D. Benvenuto, F. Broccolo, R. Cauda, A. Caruso, S. Angeletti, M. Giovanetti, A. Cassone, J. Med. Virol. 2021, 93, 6551.
K. Hassanzadeh, P. H. Perez, J. Dragotto, L. Buccarello, F. Iorio, S. Pieraccini, G. Sancini, M. Feligioni, ACS Chem. Neurosci. 2020, 11, 2361.
P. Calligari, S. Bobone, G. Ricci, A. Bocedi, Viruses 2020, 12, 445.
C. H. S. da Costa, C. A. B. de Freitas, C. N. Alves, J. Lameira, Sci. Rep. 2022, 12, 8540.
A. Khan, H. Waris, M. Rafique, M. Suleman, A. Mohammad, S. S. Ali, T. Khan, Y. Waheed, C. Liao, D. Q. Wei, Int. J. Biol. Macromol. 2022, 200, 438.
J. Wang, S. F. Muhammad, S. Aman, A. Khan, S. Munir, M. Khan, A. Mohammad, Y. Waheed, M. Munir, L. Guo, L. Chen, D. Q. Wei, J. Biomol. Struct. Dyn. 2022. https://doi.org/10.1080/07391102.2022.2123399
J. Lin, F. A. Huma, A. Irfan, S. S. Ali, Y. Waheed, A. Mohammad, M. Munir, A. Khan, D. Q. Wei, J. Biomol. Struct. Dyn. 2022, 1.
A. Khan, D. Q. Wei, K. Kousar, J. Abubaker, S. Ahmad, J. Ali, F. Al- Mulla, S. S. Ali, N. Nizam-Uddin, S. A. Mohammad, A. Mohammad, ChemBioChem 2021, 22, 2641.
S. Dutta, B. Panthi, A. Chandra, J. Phys. Chem. B 2022, 126, 5375.
K. Nguyen, S. Chakraborty, R. A. Mansbach, B. Korber, S. Gnanakaran, Viruses 2021, 13, 927.
G. M. Torrie, J. P. Valleau, J. Comput. Phys. 1977, 23, 187.
A. C. Walls, Y. J. Park, M. A. Tortorici, A. Wall, A. T. McGuire, D. Veesler, Cell 2020, 181, 281.
T. Sztain, S. H. Ahn, A. T. Bogetti, L. Casalino, J. A. Goldsmith, E. Seitz, R. S. McCool, F. L. Kearns, F. Acosta- Reyes, S. Maji, G. Mashayekhi, J. A. McCammon, A. Ourmazd, J. Frank, J. S. McLellan, L. T. Chong, R. E. Amaro, Nat. Chem. 2021, 13, 963.
A. R. Mehdipour, G. Hummer, Proc. Natl. Acad. Sci. U. S. A. 2021, 118, e2100425118.
S. Pundir, M. J. Martin, C. O'Donovan, Methods Mol. Biol. 2017, 1558, 41.
M. P. Jacobson, D. L. Pincus, C. S. Rapp, T. J. F. Day, B. Honig, D. E. Shaw, R. A. Friesner, Proteins: Struct., Funct., Genet. 2004, 55, 351.
http://www.uniprot.org/ with entry ID P0DTC2.
R. B. Best, X. Zhu, J. Shim, P. E. M. Lopes, J. Mittal, M. Feig, A. D. MacKerell, J. Chem. Theory Comput. 2012, 8, 3257.
S. Jo, T. Kim, V. G. Iyer, W. Im, J. Comput. Chem. 1859, 2008, 29.
B. R. Brooks, C. L. Brooks III, A. J. Mackerell Jr., L. Nilsson, R. J. Petrella, B. Roux, Y. Won, G. Archontis, C. Bartels, S. Boresch, A. Caflisch, L. Caves, Q. Cui, A. R. Dinner, M. Feig, S. Fischer, J. Gao, M. Hodoscek, W. Im, K. Kuczera, T. Lazaridis, J. Ma, V. Ovchinnikov, E. Paci, R. W. Pastor, C. B. Post, J. Z. Pu, M. Schaefer, B. Tidor, R. M. Venable, H. L. Woodcock, X. Wu, W. Yang, D. M. York, M. Karplus, J. Comput. Chem. 2009, 30, 1545.
J. Lee, X. Cheng, J. M. Swails, M. S. Yeom, P. K. Eastman, J. A. Lemkul, S. Wei, J. Buckner, J. C. Jeong, Y. Qi, S. Jo, V. S. Pande, D. A. Case, C. L. Brooks, A. D. MacKerell, J. B. Klauda, W. Im, J. Chem. Theory Comput. 2016, 12, 405.
S. Jo, X. Cheng, S. M. Islam, L. Huang, H. Rui, A. Zhu, H. S. Lee, Y. Qi, W. Han, K. Vanommeslaeghe, A. D. MacKerell Jr., B. Roux, W. Im, Adv. Protein Chem. Struct. Biol. 2014, 96, 235.
S. Jo, K. C. Song, H. Desaire, A. D. J. MacKerell, W. Im, J. Comput. Chem. 2011, 32, 3135.
S. J. Park, J. Lee, D. S. Patel, H. Ma, H. S. Lee, S. Jo, W. Im, Bioinformatics 2017, 33, 3051.
S. Jo, W. Im, Nucleic Acids Res. 2013, 41, D470.
S. J. Park, J. Lee, Y. Qi, N. R. Kern, H. S. Lee, S. Jo, I. Joung, K. Joo, J. Lee, W. Im, Glycobiology 2019, 29, 320.
D. A. Case, I. Y. Ben-Shalom, S. R. Brozell, D. S. Cerutti, T. E. Cheatham III, V. W. D. Cruzeiro, T. A. Darden, R. E. Duke, D. Ghoreishi, M. K. Gilson, H. Gohlke, A. W. Goetz, D. Greene, R. Harris, N. Homeyer, Y. Huang, S. Izadi, A. Kovalenko, T. Kurtzman, T. S. Lee, S. LeGrand, P. Li, C. Lin, J. Liu, T. Luchko, R. Luo, D. J. Mermelstein, K. M. Merz, Y. Miao, G. Monard, C. Nguyen, H. Nguyen, I. Omelyan, A. Onufriev, F. Pan, R. Qi, D. R. Roe, A. Roitberg, C. Sagui, S. Schott-Verdugo, J. Shen, C. L. Simmerling, J. Smith, R. SalomonFerrer, J. Swails, R. C. Walker, J. Wang, H. Wei, R. M. Wolf, X. Wu, L. Xiao, D. M. York, P. A. Kollman, Amber 18, University of California, San Francisco, CA 2018.
D. A. Case, T. E. Cheatham III, T. Darden, H. Gohlke, R. Luo, K. M. Merz Jr., A. Onufriev, C. Simmerling, B. Wang, R. J. Woods, J. Comput. Chem. 2005, 26, 1668.
A. W. Gotz, M. J. Williamson, D. Xu, D. Poole, S. Le Grand, R. C. Walker, J. Chem. Theory Comput. 2012, 8, 1542.
R. Salomon-Ferrer, A. W. Götz, D. Poole, S. Le Grand, R. C. Walker, J. Chem. Theory Comput. 2013, 9, 3878.
J. A. Maier, C. Martinez, K. Kasavajhala, L. Wickstrom, K. E. Hauser, C. Simmerling, J. Chem. Theory Comput. 2015, 11, 3696.
W. L. Jorgensen, J. Chandrasekhar, J. Madura, M. L. Klein, J. Chem. Phys. 1983, 79, 926.
U. Essmann, L. Perera, M. L. Berkowitz, T. Darden, H. Lee, L. G. Pedersen, J. Chem. Phys. 1995, 103, 8577.
C. S. Liu, J. Appl. Math. 2013, 2013, 15.
M. P. Allen, D. J. Tildesley, Computer Simulation of Liquids, Oxford University Press, New York 2017.
M. Yoneya, H. J. C. Berendsen, K. Hirasawa, Mol. Simul. 1994, 13, 395.
W. Humphrey, A. Dalke, K. Schulten, J. Mol. Graph. 1996, 14, 33.
D. Frishman, P. Argos, Proteins: Struct., Funct., Genet. 1995, 23, 566.
A. Varshney, F. P. Brooks, W. V. Wright, IEEE Comput. Graph. Appl. 1994, 14, 19.
J. Stone. M.Sc. Thesis, Computer Science Department, University of Missouri-Rolla. 1998.
J. Kastner, Wiley Interdiscip. Rev. Comput. Mol. Sci. 2011, 1, 932.
W. You, Z. Tang, C. A. Chang, J. Chem. Theory Comput. 2019, 15, 2433.
S. Kumar, D. Bouzida, R. H. Swendsen, P. A. Kollman, J. M. J. Rosenberg, J. Comput. Chem. 1992, 13, 1011.
A. Grossfield. WHAM: the weighted histogram analysis method, ver. 2.0.10. http://membrane.urmc.rochester.edu/wordpress/?pageid/126
Y. Wu, R. Qian, Y. Yang, Y. Sheng, W. Li, W. Wang, ACS Omega 2021, 6, 23432.
L. Fallon, K. A. A. Belfon, L. Raguette, Y. Wang, D. Stepanenko, A. Cuomo, J. Guerra, S. Budhan, S. Varghese, C. P. Corbo, R. C. Rizzo, C. Simmerling, J. Am. Chem. Soc. 2021, 143, 11349.