The Molecular Dynamics Study on the stability of Elk Prion Protein

Abstract

Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are fatal and highly contagious neurodegenerative diseases, of which the misfolding and aggregation of the prion protein is the only pathogenic factor. After undergoing a specific conformational change. the ubiquitous intracellular prion protein (PrPC) can transform into a pathogenic conformation PrPSc, and subsequently leads to these devastating diseases. However, the details of the conformational conversion from PrPC to PrPSc are still undiscovered. In this work, molecular dynamics (MD)and steered molecular dynamics (SMD)simulations were combined to study the stability of elk prion protein (ePrPC). There is a coiled structure with the helical tendency and the random distortion of the β-sheets in the elk prion protein and these changes can provide a structural basis for the study of the transformation from PrPC to PrPSc. The elk prion protein, in the meantime, maintains its structural stability through the formation of a rigid mesh structure and the coordination of the loose loop structure, and achieves the purpose of supporting its biological activity. Our results can help to further understanding of the pathogenic mechanism of prion protein and contribute to designing and screening drugs against TSE diseases from a structural perspective.