Constant-pH molecular dynamics simulations reveal a β-rich form of the human prion protein.

@article{Campos2010ConstantpHMD,
  title={Constant-pH molecular dynamics simulations reveal a β-rich form of the human prion protein.},
  author={Sara R. R. Campos and Miguel Machuqueiro and Ant{\'o}nio M. Baptista},
  journal={The journal of physical chemistry. B},
  year={2010},
  volume={114 39},
  pages={12692-700}
}
The misfolding of the prion protein (PrP) into a pathogenic β-rich form (PrP(Sc)) has been suggested to occur in the endocytic pathway, triggered by low pH. In this work we performed several constant-pH molecular dynamics simulations of human PrP 90-231 in the pH range 2-7, totaling more than 2 μs. We observed a strong conformational pH dependence where on average the helix content decreased and the β content increased toward acidic pH. Unlike some proposed models, the flexible N-terminus… CONTINUE READING