Molecular Dynamics Studies of Dog Prion Protein Wild-type and Its D159N Mutant

TL;DR

This study uses molecular dynamics to compare wild-type and D159N mutant dog prion proteins, revealing insights into their structural stability and resistance to prion diseases, which could inform future therapeutic strategies.

Contribution

It provides the first detailed molecular dynamics analysis of dog prion protein and its D159N mutant, elucidating mechanisms of disease resistance.

Findings

D159 residue plays a key role in structural stability

D159N mutation affects conformational dynamics

Results support D159's role in prion disease resistance

Abstract

Prion diseases (e.g. "mad cow" disease in cattle, chronic wasting disease in deer and elk, CJD in humans) have been a major public health concern affecting humans and almost all animals. However, dogs are strongly resistant to prion diseases. Recently, it was reported that the single (surface) residue D159 is sufficient to confer protection against protein conformational change and pathogenesis, providing conformational stability for dog prion protein (Neurobiology of Disease Volume 95 (November 2016) pages 204-209). This paper studies dog prion protein wild-type and D159N mutant through molecular dynamics techniques. Molecular dynamics results reveal sufficient structural informatics on the residue at position 159 to understand the mechanism underlying the resistance to prion diseases of dogs.