Pathogenesis studies have revealed that H187R mutation of human prion protein (huPrP) is related to GSS type of TSE diseases. Its pathogenic mechanism is still unclear. We here studied the globular domain of this mutant protein by molecular dynamics simulations. Compared to the wide-type protein, the mutant has similar dynamics and stability profiles in our simulation. Conformational rearrangements are concentrated around the mutation site, due to the introduction the positively charged side chain of Arg187. The strong electrostatic repulsion between Arg156 and Arg187 drives both side chains away from their original positions, leaving its hydrophobic core to be solvent accessible. Such a unfavorable conformational change may destabilize the mutant protein and make it more susceptible to unfolding.

Key words: Hydrophobic core; Molecular dynamics; Prion protein; Stability.