Misfolding pathways of the prion protein probed by molecular dynamics simulations.

ABSTRACT: Although the cellular monomeric form of the benign prion protein is now well characterized, a model for the monomer of the misfolded conformation (PrP(Sc)) remains elusive. PrP(Sc) quickly aggregates into highly insoluble fibrils making experimental structural characterization very difficult. The tendency to aggregation of PrP(Sc) in aqueous solution implies that the monomer fold must be hydrophobic. Here, by using molecular dynamics simulations, we have studied the cellular mouse prion protein and its D178N pathogenic mutant immersed in a hydrophobic environment (solution of CCl4), to reveal conformational changes and/or local structural weaknesses of the prion protein fold in unfavorable structural and thermodynamic conditions. Simulations in water have been also performed. Although obse

SUBMITTER: Barducci A 

PROVIDER: S-EPMC1305135 | biostudies-literature | 2005 Feb

REPOSITORIES: biostudies-literature