SARS-CoV-2 Spike Protein Interaction Space
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a +sense single-strand RNA virus. The virus has four major surface proteins: spike (S), envelope (E), membrane (M), and nucleocapsid (N), respectively. The constitutive proteins present a high grade of symmetry. Identifying a binding si...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/15/12058 |
| _version_ | 1797586677224439808 |
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| author | Claudiu N. Lungu Mihai V. Putz |
| author_facet | Claudiu N. Lungu Mihai V. Putz |
| author_sort | Claudiu N. Lungu |
| collection | DOAJ |
| description | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a +sense single-strand RNA virus. The virus has four major surface proteins: spike (S), envelope (E), membrane (M), and nucleocapsid (N), respectively. The constitutive proteins present a high grade of symmetry. Identifying a binding site is difficult. The virion is approximately 50–200 nm in diameter. Angiotensin-converting enzyme 2 (ACE2) acts as the cell receptor for the virus. SARS-CoV-2 has an increased affinity to human ACE2 compared with the original SAR strain. Topological space, and its symmetry, is a critical component in molecular interactions. By exploring this space, a suitable ligand space can be characterized accordingly. A spike protein (S) computational model in a complex with ACE 2 was generated using silica methods. Topological spaces were probed using high computational throughput screening techniques to identify and characterize the topological space of both SARS and SARS-CoV-2 spike protein and its ligand space. In order to identify the symmetry clusters, computational analysis techniques, together with statistical analysis, were utilized. The computations are based on crystallographic protein data bank PDB-based models of constitutive proteins. Cartesian coordinates of component atoms and some cluster maps were generated and analyzed. Dihedral angles were used in order to compute a topological receptor space. This computational study uses a multimodal representation of spike protein interactions with some fragment proteins. The chemical space of the receptors (a dimensional volume) suggests the relevance of the receptor as a drug target. The spike protein S of SARS and SARS-CoV-2 is analyzed and compared. The results suggest a mirror symmetry of SARS and SARS-CoV-2 spike proteins. The results show thatSARS-CoV-2 space is variable and has a distinct topology. In conclusion, surface proteins grant virion variability and symmetry in interactions with a potential complementary target (protein, antibody, ligand). The mirror symmetry of dihedral angle clusters determines a high specificity of the receptor space. |
| first_indexed | 2024-03-11T00:26:27Z |
| format | Article |
| id | doaj.art-6be447b35f494d2287115b8d1a3d2873 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T00:26:27Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6be447b35f494d2287115b8d1a3d28732023-11-18T22:59:49ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124151205810.3390/ijms241512058SARS-CoV-2 Spike Protein Interaction SpaceClaudiu N. Lungu0Mihai V. Putz1Department of Morphological and Functional Science, University of Medicine and Pharmacy Dunarea de Jos, Str. Alexandru Ioan Cuza No. 36, 800017 Galati, RomaniaLaboratory of Structural and Computational Physical-Chemistry for Nanosciences and QSAR, Biology-Chemistry Department, Faculty of Chemistry, Biology, Geography, West University of Timisoara, Str. Pestalozzi No. 16, 300115 Timisoara, RomaniaSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a +sense single-strand RNA virus. The virus has four major surface proteins: spike (S), envelope (E), membrane (M), and nucleocapsid (N), respectively. The constitutive proteins present a high grade of symmetry. Identifying a binding site is difficult. The virion is approximately 50–200 nm in diameter. Angiotensin-converting enzyme 2 (ACE2) acts as the cell receptor for the virus. SARS-CoV-2 has an increased affinity to human ACE2 compared with the original SAR strain. Topological space, and its symmetry, is a critical component in molecular interactions. By exploring this space, a suitable ligand space can be characterized accordingly. A spike protein (S) computational model in a complex with ACE 2 was generated using silica methods. Topological spaces were probed using high computational throughput screening techniques to identify and characterize the topological space of both SARS and SARS-CoV-2 spike protein and its ligand space. In order to identify the symmetry clusters, computational analysis techniques, together with statistical analysis, were utilized. The computations are based on crystallographic protein data bank PDB-based models of constitutive proteins. Cartesian coordinates of component atoms and some cluster maps were generated and analyzed. Dihedral angles were used in order to compute a topological receptor space. This computational study uses a multimodal representation of spike protein interactions with some fragment proteins. The chemical space of the receptors (a dimensional volume) suggests the relevance of the receptor as a drug target. The spike protein S of SARS and SARS-CoV-2 is analyzed and compared. The results suggest a mirror symmetry of SARS and SARS-CoV-2 spike proteins. The results show thatSARS-CoV-2 space is variable and has a distinct topology. In conclusion, surface proteins grant virion variability and symmetry in interactions with a potential complementary target (protein, antibody, ligand). The mirror symmetry of dihedral angle clusters determines a high specificity of the receptor space.https://www.mdpi.com/1422-0067/24/15/12058COVID-19antibodyparatopeQSARchemical spacespike protein |
| spellingShingle | Claudiu N. Lungu Mihai V. Putz SARS-CoV-2 Spike Protein Interaction Space International Journal of Molecular Sciences COVID-19 antibody paratope QSAR chemical space spike protein |
| title | SARS-CoV-2 Spike Protein Interaction Space |
| title_full | SARS-CoV-2 Spike Protein Interaction Space |
| title_fullStr | SARS-CoV-2 Spike Protein Interaction Space |
| title_full_unstemmed | SARS-CoV-2 Spike Protein Interaction Space |
| title_short | SARS-CoV-2 Spike Protein Interaction Space |
| title_sort | sars cov 2 spike protein interaction space |
| topic | COVID-19 antibody paratope QSAR chemical space spike protein |
| url | https://www.mdpi.com/1422-0067/24/15/12058 |
| work_keys_str_mv | AT claudiunlungu sarscov2spikeproteininteractionspace AT mihaivputz sarscov2spikeproteininteractionspace |