Molecular dynamics simulations of wild-type and point mutation human prion protein at normal and elevated temperature.
This paper describes molecular dynamics simulations of prion protein at 300 and 500 K. This was undertaken to gain insight into the factors involved in the stability of prion protein. Simulations were done using the Particle Mesh Ewald (PME) method using a homology model of the C-terminal fragment of human prion protein and the NMR structure of the human prion protein. The simulations at both 300 and 500 K were stable. Simulations were also undertaken with a mutant known to be associated with prion disease: Asp178Asn. The Asp178Asn simulation trajectory was observed to be much less stable than for the wild-type protein trajectory. Significant breakdown in secondary structure was observed for Asp178Asn at 500 K.
el-Bastawissy
E
E
Welsh School of Pharmacy, Cardiff University, UK.
Knaggs
M H
MH
Gilbert
I H
IH
D003198:Computer Simulation; D004355:Drug Stability; D006801:Humans; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D017354:Point Mutation; D011328:Prions / Q000737:chemistry* / Q000235:genetics*; D017433:Protein Structure, Secondary; D055672:Static Electricity; D013696:Temperature; D013816:Thermodynamics
D011328:Prions