Molecular Dynamics and Optimization Studies of Horse Prion Protein Wild Type and Its S167D Mutant

Abstract

Prion diseases, also called transmissible spongiform encephalopathies (TSEs), are fatal neurodegenerative diseases characterised by the accumulation of an abnormal prion protein isoform (PrPSc: rich in β-sheets—about 30% α-helix and 43% β-sheet), which is converted from the normal prion protein (PrPC: predominantly α-helical—about 42% α-helix and 3% β-sheet). However, prion disease has not been reported in horses up to now; therefore, horses are known to be a species resistant to prion diseases. Residue S167 in horses has been cited as a critical protective residue for encoding PrP conformational stability in prion-resistance. According to the “protein-only” hypothesis, PrPSc is responsible for both the spongiform degeneration of the brain and disease transmissibility. Thus, understanding the conformational dynamics of PrPSc from PrPC is key to developing effective therapies. This article focuses on molecular dynamics and optimization studies on the horse PrP wild type and its S167D mutant, respectively, to understand their conformational dynamics and optimized confirmation; the interesting results will be discussed.