Introducing critical residues in the human prion protein and its Asp 178 Asn mutant by molecular dynamics simulation

The molecular dynamics (MD) simulation method is used to assess structural details for humanprion protein (hereafter PrPN) and its Asp178 Asn mutant (hereafter PrPm) which causes fatalfamilial insomnia disease. The results reveal that the flexibility and instability increase in PrPmcould be related to specific amino acids exposed to the solvent. Solvation free energy of PrPm is 20kjmot1nni2 more than PrPN that is caused by solvent accessible surface area (SASA) especiallyhydrophobic area, Spho. The study of time interval properties indicates a number of critical aminoacids in prion proteins, which exposed to the solvent. They can be ideal anchor-points for initialintermolecular contacts, or affect metal-ion occupancy. The present achievements may be used indrug design for the prevention or treatment of disease..