Molecular Dynamics Studies on the Structural Stability of Wild-Type Rabbit Prion Protein: Surface Electrostatic Charge Distributions

TL;DR

This study uses molecular dynamics simulations to analyze the surface electrostatic charge distribution of rabbit prion protein over time, revealing its stability and potential implications for prion disease resistance.

Contribution

It provides the first detailed dynamic analysis of surface charge distribution in rabbit prion protein, linking electrostatic properties to structural stability.

Findings

Positive charge distribution persists during simulations

Surface charge distribution varies over time

Implications for prion disease resistance

Abstract

Prion diseases cover a large range of neurodegenerative diseases in humans and animals, which are invariably fatal and highly infectious. By now there have not been some effective therapeutic approaches or medications to treat all prion diseases. Fortunately, numerous experimental experiences have showed that rabbits are resistant to infection from prion diseases isolated from other species, and recently the molecular structures of rabbit prion protein and its mutants were released into protein data bank. Prion diseases are "protein structural conformational" diseases. Thus, in order to reveal some secrets of prion diseases, it is amenable to study rabbits by techniques of the molecular structure and its dynamics. Wen et al. (PLoS One 5(10) e13273 (2010), Journal of Biological Chemistry 285(41) 31682-31693 (2010)) reported the surface of NMR RaPrPC(124-228) molecular snapshot has a large land of continuous positive charge distribution, which contributes to the structural stability of rabbit prion protein. This is just the property at one snapshot. This paper confirms a large land of positive charge distribution has still been reserved during the long molecular dynamics of 30 nanoseconds in many environments, but the continuous of the land has not been always reserved yet. These results may be useful for the medicinal treatment of prion diseases.