Human Prion Protein Conformational Changes Susceptibility: A Molecular Dynamics Simulation Study

Abstract

Prion proteins are related to the development of incurable and invariably fatal neurodegenera-tive diseases in humans and animals. The pathogenicity involves the conversion of the host-en-coded-alpha rich isoform of prion protein, PrP C , into a misfolded beta-strand rich conformer, PrP Sc . Although it has already been described that many punctual mutations alter the stability of PrP C , making it more prone to adopt an abnormal misfolded structure, the majority of cases reported among general population are sporadic in wild-type organisms. Thus, in this work we studied the dynamics and stability profiles of wild-type human prion protein by Molecular Dynamics (MD) simulation at different solvent temperatures. This analysis brought out certain residues and seg-ments of the prion protein as critical to conformational changes; these results are consistent with experimental reports showing that protein mutants in those positions are related to the develop-ment of disease.