Abstract
Many serious medical conditions are caused by the accumulation of amyloid aggregates in tissues and organs. One of the most well-known amyloidogenic proteins is the prion protein (PrP), which may undergo conformational change between the normal cellular isoform PrPC and the aggregation-prone isoform PrPSc. Elucidation of this conformational transition is necessary for understanding the onset and propagation of prion diseases. However, the flexibility of PrP hinders its research by the experimental methods of protein structure determination. Here, we implement de novo protein modelling and molecular dynamics simulations to predict the interdomain interactions of the full-length PrPC. Our theoretical findings can serve as the basis for mutational analysis and for further studies of the amyloidogenic behavior of the prion protein.
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ACKNOWLEDGMENTS
The authors thank Dr. Stefano Piana-Agostinetti for generously providing a99SB-disp force field parameters in GROMACS format and Ms Lisa Trifonova for proofreading the manuscript.
Funding
This work was supported by the Russian Science Foundation (grant no. 19-74-20055).
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(Submitted by Vl. V. Voevodin)
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Mamchur, A.A., Panina, I.S., Yaroshevich, I.A. et al. Molecular Dynamics Simulations of the Full-Length Prion Protein. Lobachevskii J Math 41, 1502–1508 (2020). https://doi.org/10.1134/S1995080220080119
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DOI: https://doi.org/10.1134/S1995080220080119