Molecular dynamics studies of dog prion protein wild-type and its D159N mutant

Abstract

Prion diseases (e.g. ‘mad cow’ disease in cattle, chronic wasting disease in deer and elk, Creutzfeldt-Jakob disease in humans) have been a major public health concern affecting humans and almost all animals. However, dogs are strongly resistant to prion diseases. Recently, through transgenic techniques, it was reported that the single (surface) residue D159 is sufficient to confer protection against protein conformational change and pathogenesis, thus provides conformational stability for dog prion protein. This made a big breakthrough in dog prion protein research field. For dog prion protein, another advancement is the produce of its NMR structure in 2005. However, all these breakthroughs are still short of enough structural informatics of dog prion protein. This paper studies dog prion protein wild-type and D159N mutant through molecular dynamics (MD) techniques. Our MD results reveal sufficient structural informatics on the residue at position 159 to understand the mechanism underlying the resistance to prion diseases of dogs. The structural informatics of this paper should be very useful for the medicinal treatment of prion diseases.

Communicated by Ramaswamy H. Sarma

Keywords:

• Prion diseases
• immunity of dogs
• key residue D159
• wild-type and mutant
• molecular dynamics

Acknowledgements

The author is grateful to the comments from reviewers and editors, which have improved this paper greatly.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research (with project no. pb04 at Federation University Australia and under NCI) was undertaken with the assistance of resources and services from the National Computational Infrastructure (NCI), which is supported by the Australian Government.