The pH Effects on SARS-CoV and SARS-CoV-2 Spike Proteins in the Process of Binding to hACE2
COVID-19 has been threatening human health since the late 2019, and has a significant impact on human health and economy. Understanding SARS-CoV-2 and other coronaviruses is important to develop effective treatments for COVID-19 and other coronavirus-caused diseases. In this work, we applied multi-s...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/11/2/238 |
| _version_ | 1827653399948034048 |
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| author | Yixin Xie Wenhan Guo Alan Lopez-Hernadez Shaolei Teng Lin Li |
| author_facet | Yixin Xie Wenhan Guo Alan Lopez-Hernadez Shaolei Teng Lin Li |
| author_sort | Yixin Xie |
| collection | DOAJ |
| description | COVID-19 has been threatening human health since the late 2019, and has a significant impact on human health and economy. Understanding SARS-CoV-2 and other coronaviruses is important to develop effective treatments for COVID-19 and other coronavirus-caused diseases. In this work, we applied multi-scale computational approaches to study the electrostatic features of spike (S) proteins for SARS-CoV and SARS-CoV-2. From our results, we found that SARS-CoV and SARS-CoV-2 have similar charge distributions and electrostatic features when binding with the human angiotensin-converting enzyme 2 (hACE2). Energy pH-dependence calculations revealed that the complex structures of hACE2 and the S proteins of SARS-CoV/SARS-CoV-2 are stable at pH values ranging from 7.5 to 9. Three independent 100 ns molecular dynamics (MD) simulations were performed using NAMD to investigate the hydrogen bonds between S proteins RBD and hACE2 RBD. From MD simulations, we found that SARS-CoV-2 forms 19 pairs (average of three simulations) of hydrogen bonds with high occupancy (>50%) to hACE2, compared to 16 pairs between SARS-CoV and hACE2. Additionally, SARS-CoV viruses prefer sticking to the same hydrogen bond pairs, while SARS-CoV-2 tends to have a larger range of selections on hydrogen bonds acceptors. We also labelled key residues involved in forming the top five hydrogen bonds that were found in all three independent 100 ns simulations. This identification is important to potential drug designs for COVID-19 treatments. Our work will shed the light on current and future coronavirus-caused diseases. |
| first_indexed | 2024-03-09T21:17:22Z |
| format | Article |
| id | doaj.art-de98d467caca46cdb1d21fb8eed27802 |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-09T21:17:22Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-de98d467caca46cdb1d21fb8eed278022023-11-23T21:32:32ZengMDPI AGPathogens2076-08172022-02-0111223810.3390/pathogens11020238The pH Effects on SARS-CoV and SARS-CoV-2 Spike Proteins in the Process of Binding to hACE2Yixin Xie0Wenhan Guo1Alan Lopez-Hernadez2Shaolei Teng3Lin Li4Computational Science Program, University of Texas at El Paso, El Paso, TX 79912, USAComputational Science Program, University of Texas at El Paso, El Paso, TX 79912, USAComputational Science Program, University of Texas at El Paso, El Paso, TX 79912, USADepartment of Biology, Howard University, Washington, DC 20059, USAComputational Science Program, University of Texas at El Paso, El Paso, TX 79912, USACOVID-19 has been threatening human health since the late 2019, and has a significant impact on human health and economy. Understanding SARS-CoV-2 and other coronaviruses is important to develop effective treatments for COVID-19 and other coronavirus-caused diseases. In this work, we applied multi-scale computational approaches to study the electrostatic features of spike (S) proteins for SARS-CoV and SARS-CoV-2. From our results, we found that SARS-CoV and SARS-CoV-2 have similar charge distributions and electrostatic features when binding with the human angiotensin-converting enzyme 2 (hACE2). Energy pH-dependence calculations revealed that the complex structures of hACE2 and the S proteins of SARS-CoV/SARS-CoV-2 are stable at pH values ranging from 7.5 to 9. Three independent 100 ns molecular dynamics (MD) simulations were performed using NAMD to investigate the hydrogen bonds between S proteins RBD and hACE2 RBD. From MD simulations, we found that SARS-CoV-2 forms 19 pairs (average of three simulations) of hydrogen bonds with high occupancy (>50%) to hACE2, compared to 16 pairs between SARS-CoV and hACE2. Additionally, SARS-CoV viruses prefer sticking to the same hydrogen bond pairs, while SARS-CoV-2 tends to have a larger range of selections on hydrogen bonds acceptors. We also labelled key residues involved in forming the top five hydrogen bonds that were found in all three independent 100 ns simulations. This identification is important to potential drug designs for COVID-19 treatments. Our work will shed the light on current and future coronavirus-caused diseases.https://www.mdpi.com/2076-0817/11/2/238SARS-CoVSARS-CoV-2COVID-19electrostatic featuresAngiotensin-Converting Enzyme 2hACE2 |
| spellingShingle | Yixin Xie Wenhan Guo Alan Lopez-Hernadez Shaolei Teng Lin Li The pH Effects on SARS-CoV and SARS-CoV-2 Spike Proteins in the Process of Binding to hACE2 Pathogens SARS-CoV SARS-CoV-2 COVID-19 electrostatic features Angiotensin-Converting Enzyme 2 hACE2 |
| title | The pH Effects on SARS-CoV and SARS-CoV-2 Spike Proteins in the Process of Binding to hACE2 |
| title_full | The pH Effects on SARS-CoV and SARS-CoV-2 Spike Proteins in the Process of Binding to hACE2 |
| title_fullStr | The pH Effects on SARS-CoV and SARS-CoV-2 Spike Proteins in the Process of Binding to hACE2 |
| title_full_unstemmed | The pH Effects on SARS-CoV and SARS-CoV-2 Spike Proteins in the Process of Binding to hACE2 |
| title_short | The pH Effects on SARS-CoV and SARS-CoV-2 Spike Proteins in the Process of Binding to hACE2 |
| title_sort | ph effects on sars cov and sars cov 2 spike proteins in the process of binding to hace2 |
| topic | SARS-CoV SARS-CoV-2 COVID-19 electrostatic features Angiotensin-Converting Enzyme 2 hACE2 |
| url | https://www.mdpi.com/2076-0817/11/2/238 |
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