Article ; Online: Unraveling the stability landscape of mutations in the SARS-CoV-2 receptor-binding domain.
2021 Volume 11, Issue 1, Page(s) 9166
Abstract: The interaction between the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein and ... We unravel the mutation landscape of the receptor region and assess the toxicity potential of single and ... point mutations in the RBD and computationally explore mutations that can affect the binding with the ACE2 enzyme ...
| Abstract | The interaction between the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein and the ACE2 enzyme is believed to be the entry point of the virus into various cells in the body, including the lungs, heart, liver, and kidneys. The current focus of several therapeutic design efforts explores attempts at affecting the binding potential between the two proteins to limit the activity of the virus and disease progression. In this work, we analyze the stability of the spike protein under all possible single-point mutations in the RBD and computationally explore mutations that can affect the binding with the ACE2 enzyme. We unravel the mutation landscape of the receptor region and assess the toxicity potential of single and multi-point mutations, generating insights for future vaccine efforts on mutations that might further stabilize the spike protein and increase its infectivity. We developed a tool, called SpikeMutator, to construct full atomic protein structures of the mutant spike proteins and shared a database of 3800 single-point mutant structures. We analyzed the recent 65,000 reported spike sequences across the globe and observed the emergence of stable multi-point mutant structures. Using the landscape, we searched through 7.5 million possible 2-point mutation combinations and report that the (R355D K424E) mutation produces one of the strongest spike proteins that therapeutic efforts should investigate for the sake of developing effective vaccines. |
|---|---|
| MeSH term(s) | Angiotensin-Converting Enzyme 2/metabolism ; Binding Sites ; Computational Biology/methods ; Humans ; Models, Molecular ; Molecular Dynamics Simulation ; Mutation ; Protein Conformation ; Protein Stability ; SARS-CoV-2/genetics ; SARS-CoV-2/isolation & purification ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/metabolism |
| Chemical Substances | Spike Glycoprotein, Coronavirus ; spike glycoprotein, SARS-CoV ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) |
| Language | English |
| Publishing date | 2021-04-28 |
| Publishing country | England |
| Document type | Journal Article |
| ZDB-ID | 2615211-3 |
| ISSN | 2045-2322 ; 2045-2322 |
| ISSN (online) | 2045-2322 |
| ISSN | 2045-2322 |
| DOI | 10.1038/s41598-021-88696-5 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.