Contact residue contributions to interaction energies between SARS-CoV-1 spike proteins and human ACE2 receptors
Abstract Several viruses of the corona family interact, via their spike (S) proteins, with human cellular receptors. Spike proteins of SARS-CoV-1 and SARS-CoV-2 virions, being structurally related but not identical, mediate attachment to the human angiotensin-converting enzyme 2 (hACE2) receptor in...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-020-80942-6 |
| _version_ | 1818750530061598720 |
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| author | Jorge H. Rodriguez Akshita Gupta |
| author_facet | Jorge H. Rodriguez Akshita Gupta |
| author_sort | Jorge H. Rodriguez |
| collection | DOAJ |
| description | Abstract Several viruses of the corona family interact, via their spike (S) proteins, with human cellular receptors. Spike proteins of SARS-CoV-1 and SARS-CoV-2 virions, being structurally related but not identical, mediate attachment to the human angiotensin-converting enzyme 2 (hACE2) receptor in similar but non-identical ways. Molecular-level understanding of interactions between spike proteins and hACE2 can aid strategies for blocking attachment of SARS-CoV-1, a potentially reemerging health threat, to human cells. We have identified dominant molecular-level interactions, some attractive and some repulsive, between the receptor binding domain of SARS-CoV-1 spike proteins (S-RBD) and hACE2. We performed fragment-based quantum-biochemical calculations which directly relate biomolecular structure to the hACE2...S-RBD interaction energy. Consistent with X-ray crystallography and cryo-EM, the interaction energy between hACE2 and S-RBD ( $$\approx -$$ ≈ - 26 kcal/mol) corresponds to a net intermolecular attraction which is significantly enhanced by inclusion of dispersion van der Waals forces. Protein fragments at the hACE2...S-RBD interface, that dominate host-virus attraction, have been identified together with their constituent amino acid residues. Two hACE2 fragments which include residues (GLU37, ASP38, TYR41, GLN42) and (GLU329, LYS353, GLY354), respectively, as well as three S-RBD fragments which include residues (TYR436), (ARG426) and (THR487, GLY488, TYR491), respectively, have been identified as primary attractors at the hACE2...S-RBD interface. |
| first_indexed | 2024-12-18T04:21:08Z |
| format | Article |
| id | doaj.art-18044c32fd9a4bbc9757c788d956b9e8 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T04:21:08Z |
| publishDate | 2021-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-18044c32fd9a4bbc9757c788d956b9e82022-12-21T21:21:13ZengNature PortfolioScientific Reports2045-23222021-01-0111111210.1038/s41598-020-80942-6Contact residue contributions to interaction energies between SARS-CoV-1 spike proteins and human ACE2 receptorsJorge H. Rodriguez0Akshita Gupta1Computational Biomolecular Physics Group, Department of Physics and Astronomy, Purdue UniversityComputational Biomolecular Physics Group, Department of Physics and Astronomy, Purdue UniversityAbstract Several viruses of the corona family interact, via their spike (S) proteins, with human cellular receptors. Spike proteins of SARS-CoV-1 and SARS-CoV-2 virions, being structurally related but not identical, mediate attachment to the human angiotensin-converting enzyme 2 (hACE2) receptor in similar but non-identical ways. Molecular-level understanding of interactions between spike proteins and hACE2 can aid strategies for blocking attachment of SARS-CoV-1, a potentially reemerging health threat, to human cells. We have identified dominant molecular-level interactions, some attractive and some repulsive, between the receptor binding domain of SARS-CoV-1 spike proteins (S-RBD) and hACE2. We performed fragment-based quantum-biochemical calculations which directly relate biomolecular structure to the hACE2...S-RBD interaction energy. Consistent with X-ray crystallography and cryo-EM, the interaction energy between hACE2 and S-RBD ( $$\approx -$$ ≈ - 26 kcal/mol) corresponds to a net intermolecular attraction which is significantly enhanced by inclusion of dispersion van der Waals forces. Protein fragments at the hACE2...S-RBD interface, that dominate host-virus attraction, have been identified together with their constituent amino acid residues. Two hACE2 fragments which include residues (GLU37, ASP38, TYR41, GLN42) and (GLU329, LYS353, GLY354), respectively, as well as three S-RBD fragments which include residues (TYR436), (ARG426) and (THR487, GLY488, TYR491), respectively, have been identified as primary attractors at the hACE2...S-RBD interface.https://doi.org/10.1038/s41598-020-80942-6 |
| spellingShingle | Jorge H. Rodriguez Akshita Gupta Contact residue contributions to interaction energies between SARS-CoV-1 spike proteins and human ACE2 receptors Scientific Reports |
| title | Contact residue contributions to interaction energies between SARS-CoV-1 spike proteins and human ACE2 receptors |
| title_full | Contact residue contributions to interaction energies between SARS-CoV-1 spike proteins and human ACE2 receptors |
| title_fullStr | Contact residue contributions to interaction energies between SARS-CoV-1 spike proteins and human ACE2 receptors |
| title_full_unstemmed | Contact residue contributions to interaction energies between SARS-CoV-1 spike proteins and human ACE2 receptors |
| title_short | Contact residue contributions to interaction energies between SARS-CoV-1 spike proteins and human ACE2 receptors |
| title_sort | contact residue contributions to interaction energies between sars cov 1 spike proteins and human ace2 receptors |
| url | https://doi.org/10.1038/s41598-020-80942-6 |
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