Computational approaches to explore bacterial toxin entry into the host cell

Weria Pezeshkian*, Julian C. Shillcock, John H. Ipsen

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Abstrakt

Many bacteria secrete toxic protein complexes that modify and disrupt essential processes in the infected cell that can lead to cell death. To conduct their action, these toxins often need to cross the cell membrane and reach a specific substrate inside the cell. The investigation of these protein complexes is essential not only for understanding their biological functions but also for the rational design of targeted drug delivery vehicles that must navigate across the cell membrane to deliver their therapeutic payload. Despite the immense advances in experimental techniques, the investigations of the toxin entry mechanism have remained challenging. Computer simulations are robust complementary tools that allow for the exploration of biological processes in exceptional detail. In this review, we first highlight the strength of computational methods, with a special focus on all-atom molecular dynamics, coarse-grained, and mesoscopic models, for exploring different stages of the toxin protein entry mechanism. We then summarize recent developments that are significantly advancing our understanding, notably of the glycolipid–lectin (GL-Lect) endocytosis of bacterial Shiga and cholera toxins. The methods discussed here are also applicable to the design of membrane-penetrating nanoparticles and the study of the phenomenon of protein phase separation at the surface of the membrane. Finally, we discuss other likely routes for future development.

OriginalsprogEngelsk
Artikelnummer449
TidsskriftToxins
Vol/bind13
Udgave nummer7
Antal sider9
ISSN2072-6651
DOI
StatusUdgivet - jul. 2021

Bibliografisk note

Funding Information:
Acknowledgments: JCS was supported by funding to the Blue Brain Project, a research centre of the École polytechnique fédérale de Lausanne (EPFL), from the Swiss government’s ETH Board of the Swiss Federal Institutes of Technology.

Funding Information:
JCS was supported by funding to the Blue Brain Project, a research centre of the ?cole polytechnique f?d?rale de Lausanne (EPFL), from the Swiss government?s ETH Board of the Swiss Federal Institutes of Technology.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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