2024
DOI: 10.1101/2024.05.14.594247
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Tuning single-molecule ClyA nanopore tweezers for real-time tracking of the conformational dynamics of West Nile viral NS2B/NS3 protease

Spencer A. Shorkey,
Yumeng Zhang,
Jacqueline Sharp
et al.

Abstract: The flaviviral NS2B/NS3 protease is a conserved enzyme required for flavivirus replication. Its highly dynamic conformation poses major challenges but also offers opportunities for antiviral inhibition. Here, we established a nanopore tweezers-based platform to monitor NS2B/NS3 conformational dy-namics in real-time. Molecular simulations coupled with electrophysiology revealed that the protease could be captured in the middle of the ClyA nanopore lumen, stabilized mainly by dynamic electro-static interactions.… Show more

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