Molecular dynamics study on the stability of wild-type and the R220K mutant of human prion protein

Abstract

Prion diseases are invariably fatal and highly infectious neurodegenerative diseases related to the structure transition of α-helix into β-sheet. In order to gain more direct insight into the molecular basis of the disease, the stability of the wild-type human prion protein (hPrPc) and the R220K mutant (m-hPrPc) was studied by molecular dynamics (MD) and flow MD simulation. Both the thermodynamic stability and the mechanical properties of hPrPc were investigated in this work. It was found that β-sheet was more readily to be unfolded in m-hPrPc. In the case of hPrPc, less content of helix was preserved after water turbulence. The H-bond network formed by the mutation-related residue 220 was found to play a key role in the stability of hPrPc.

Keywords::

• stability
• mutant
• molecular dynamics simulation
• hydrodynamics
• human prion protein

Acknowledgement

This work was financially supported by the National Natural Science Foundation of China (Grant No. 21003037).