  Prion diseases or called transmissible spongiform encephalopathies are fatal
neurodegenerative diseases characterised by the accumulation of an abnormal
prion protein isoform (rich in beta-sheets - about 30% alpha-helix and 43%
beta-sheet), which is converted from the normal prion protein (predominant in
alpha-helix - about 42% alpha-helix and 3% beta-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 horse has been cited as
critical protective residue for encoding prion protein conformational stability
in prion-resistance. According to the protein-only hypothesis, abnormal prion
protein is responsible for both spongiform degeneration of the brain and
disease transmissibility. Thus, understanding the conformational dynamics of
abnormal prion protein from normal prion protein is a key to developing
effective therapies. This article is to do molecular dynamics and optimization
studies on the horse normal prion protein wild-type and its S167D mutant
respectively to understand their conformational dynamics and optimized
confirmation; interesting results will be discussed.
