Molecular dynamics and optimization studies of horse prion protein wild type and its S167D mutant

Abstract

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.