Fate of pathological prion (PrP^sc92–138) in soil and water: prion-clay nanoparticle molecular dynamics

Abstract

Pathogenic prion protein scrapie (PrP^sc) may contaminate soils for decades and remain in water in colloidal suspension, providing infection pathways for animals through the inhalation of ingested dust and soil particles, and drinking water. We used molecular dynamics simulations to understand the strong binding mechanism of this pathogenic peptide with clay mineral surfaces and compared our results to experimental works. We restricted our model to the moiety PrP(92–138), which is a portion of the whole PrP^sc molecule responsible for infectivity and modeled it using explicit solvating water molecules in contact with a pyrophyllite cleavage plane. Pyrophyllite is taken as a model for common soil clay, but it has no permanent structural charge. However, partial residual negative charges occur on the cleavage plane slab surface due to a slab charge unbalance. The charge is isotropic in 2D and it was balanced with K⁺ ions. After partially removing potassium ions, the peptide anchors to the clay surface via up to 10 hydrogen bonds, between protonated lysine or histidine residues and the oxygen atoms of the siloxane cavities. Our results provide insight to the mechanism responsible for the strong association between the PrP^sc peptide and clay nanoparticles and the associations present in contaminated soil and water which may lead to the infection of animals.

Keywords:

• molecular dynamics
• prion’ diseases
• nanoparticules
• adsorption prion/clay
• smectite

Acknowledgments

This study was funded by the European Commission FP5 Quality of Life program (FatePride; QLRT-2001-02723). N.S. acknowledges funding from the US National Science Foundation for CAREER grant EAR 0346689, NSF DMR grant 0906817, University of Akron Start-Up Funds, and the Université Joseph Fourier (UJF) Visiting Professor Fellowship. L.C. acknowledges the IUF endowment chair. We are grateful for fruitful discussions with Dr. David Brown and other scientists of the FatePride group.

Notes

In memoriam, to Professor Dominique Dormont, a pioneer in Prion research (10th anniversary of his death).