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Allosteric regulation is common in protein–protein interactions and is thus promising in drug design. Previous experimental and simulation work supported the presence of allosteric regulation in the SARS-CoV-2 spike protein. Here the route of allosteric regulation in SARS-CoV-2 spike protein is examined by all-atom explicit solvent molecular dynamics simulations, contrastive machine learning, and the Ohm approach. It was found that peptide binding to the polybasic cleavage sites, especially the one at the first subunit of the trimeric spike protein, activates the fluctuation of the spike protein's backbone, which eventually propagates to the receptor-binding domain on the third subunit that binds to ACE2. Remarkably, the allosteric regulation routes starting from the polybasic cleavage sites share a high fraction (39–67%) of the critical amino acids with the routes starting from the nitrogen-terminal domains, suggesting the presence of an allosteric regulation network in the spike protein. Our study paves the way for the rational design of allosteric antibody inhibitors.
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SARS‐CoV ‐2 spike protein capture by peptide functionalized networks
Abstract Coronavirus disease 2019 (COVID‐19) has significantly impacted human health, the global economy, and society. Viruses residing on common surfaces represent a potential source of contamination for the general population. Spike binding peptide 1, SBP1 is a 23 amino acid peptide, which has micromolar binding affinity (1.3 μM) towards the spike protein receptor‐binding domain. We hypothesize that if we can covalently immobilize this SBP1 peptide in a covalent crosslinked network system, we can develop a surface that would preferentially bind spike protein and, therefore, which could limit viral spread. A series of covalently crosslinked networks of hydroxy ethyl acrylate (HEA) with different primary chain lengths and crosslinker density was prepared. Later, this network system was functionalized using 2% SBP1 peptide. Our study found that with a shorter chain length and lower crosslinker density, the HEA network system alone could capture almost 80% of the spike protein. We reported that the efficiency could be enhanced almost by 17% with higher crosslinker density.
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- PAR ID:
- 10399683
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Journal of Polymer Science
- Volume:
- 61
- Issue:
- 5
- ISSN:
- 2642-4150
- Page Range / eLocation ID:
- p. 391-397
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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