Three-Dimensional Structural Stability and Local Electrostatic Potential at Point Mutations in Spike Protein of SARS-CoV-2 Coronavirus
The contagiousness of SARS-CoV-2 β-coronavirus is determined by the virus–receptor electrostatic association of its positively charged spike (S) protein with the negatively charged angiotensin converting enzyme-2 (ACE2 receptor) of the epithelial cells. If some mutations occur, the electrostatic pot...
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MDPI AG
2024-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/4/2174 |
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| author | Svetlana H. Hristova Alexandar M. Zhivkov |
| author_facet | Svetlana H. Hristova Alexandar M. Zhivkov |
| author_sort | Svetlana H. Hristova |
| collection | DOAJ |
| description | The contagiousness of SARS-CoV-2 β-coronavirus is determined by the virus–receptor electrostatic association of its positively charged spike (S) protein with the negatively charged angiotensin converting enzyme-2 (ACE2 receptor) of the epithelial cells. If some mutations occur, the electrostatic potential on the surface of the receptor-binding domain (RBD) could be altered, and the S-ACE2 association could become stronger or weaker. The aim of the current research is to investigate whether point mutations can noticeably alter the electrostatic potential on the RBD and the 3D stability of the S1-subunit of the S-protein. For this purpose, 15 mutants with different hydrophilicity and electric charge (positive, negative, or uncharged) of the substituted and substituting amino acid residues, located on the RBD at the S1-ACE2 interface, are selected, and the 3D structure of the S1-subunit is reconstructed on the base of the crystallographic structure of the S-protein of the wild-type strain and the amino acid sequence of the unfolded polypeptide chain of the mutants. Then, the Gibbs free energy of folding, isoelectric point, and pH-dependent surface electrostatic potential of the S1-subunit are computed using programs for protein electrostatics. The results show alterations in the local electrostatic potential in the vicinity of the mutant amino acid residue, which can influence the S-ACE2 association. This approach allows prediction of the relative infectivity, transmissibility, and contagiousness (at equal social immune status) of new SARS-CoV-2 mutants by reconstruction of the 3D structure of the S1-subunit and calculation of the surface electrostatic potential. |
| first_indexed | 2024-03-07T22:28:52Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-07T22:28:52Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b04204d6b4a049deaa0b1d3fd8f17a6c2024-02-23T15:20:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-02-01254217410.3390/ijms25042174Three-Dimensional Structural Stability and Local Electrostatic Potential at Point Mutations in Spike Protein of SARS-CoV-2 CoronavirusSvetlana H. Hristova0Alexandar M. Zhivkov1Department of Medical Physics and Biophysics, Medical Faculty, Medical University—Sofia, Zdrave Street 2, 1431 Sofia, BulgariaScientific Research Center, “St. Kliment Ohridski” Sofia University, 8 Dragan Tsankov Blvd., 1164 Sofia, BulgariaThe contagiousness of SARS-CoV-2 β-coronavirus is determined by the virus–receptor electrostatic association of its positively charged spike (S) protein with the negatively charged angiotensin converting enzyme-2 (ACE2 receptor) of the epithelial cells. If some mutations occur, the electrostatic potential on the surface of the receptor-binding domain (RBD) could be altered, and the S-ACE2 association could become stronger or weaker. The aim of the current research is to investigate whether point mutations can noticeably alter the electrostatic potential on the RBD and the 3D stability of the S1-subunit of the S-protein. For this purpose, 15 mutants with different hydrophilicity and electric charge (positive, negative, or uncharged) of the substituted and substituting amino acid residues, located on the RBD at the S1-ACE2 interface, are selected, and the 3D structure of the S1-subunit is reconstructed on the base of the crystallographic structure of the S-protein of the wild-type strain and the amino acid sequence of the unfolded polypeptide chain of the mutants. Then, the Gibbs free energy of folding, isoelectric point, and pH-dependent surface electrostatic potential of the S1-subunit are computed using programs for protein electrostatics. The results show alterations in the local electrostatic potential in the vicinity of the mutant amino acid residue, which can influence the S-ACE2 association. This approach allows prediction of the relative infectivity, transmissibility, and contagiousness (at equal social immune status) of new SARS-CoV-2 mutants by reconstruction of the 3D structure of the S1-subunit and calculation of the surface electrostatic potential.https://www.mdpi.com/1422-0067/25/4/2174SARS-CoV-2coronavirus variantspoint mutationsS-proteinACE2 receptorprotein electrostatics |
| spellingShingle | Svetlana H. Hristova Alexandar M. Zhivkov Three-Dimensional Structural Stability and Local Electrostatic Potential at Point Mutations in Spike Protein of SARS-CoV-2 Coronavirus International Journal of Molecular Sciences SARS-CoV-2 coronavirus variants point mutations S-protein ACE2 receptor protein electrostatics |
| title | Three-Dimensional Structural Stability and Local Electrostatic Potential at Point Mutations in Spike Protein of SARS-CoV-2 Coronavirus |
| title_full | Three-Dimensional Structural Stability and Local Electrostatic Potential at Point Mutations in Spike Protein of SARS-CoV-2 Coronavirus |
| title_fullStr | Three-Dimensional Structural Stability and Local Electrostatic Potential at Point Mutations in Spike Protein of SARS-CoV-2 Coronavirus |
| title_full_unstemmed | Three-Dimensional Structural Stability and Local Electrostatic Potential at Point Mutations in Spike Protein of SARS-CoV-2 Coronavirus |
| title_short | Three-Dimensional Structural Stability and Local Electrostatic Potential at Point Mutations in Spike Protein of SARS-CoV-2 Coronavirus |
| title_sort | three dimensional structural stability and local electrostatic potential at point mutations in spike protein of sars cov 2 coronavirus |
| topic | SARS-CoV-2 coronavirus variants point mutations S-protein ACE2 receptor protein electrostatics |
| url | https://www.mdpi.com/1422-0067/25/4/2174 |
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