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

Document Type : Research Paper




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