NR AXNF
AU Gill,A.C.; Kirby,L.
TI Molecular Dynamics Simulations of Prion Protein Variants
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Protein Misfolding P01.20
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
At the Neuropathogenesis Unit, we make use of a variety of techniques to investigate the effect of mutations and polymorphisms in the gene encoding the prion protein, including the use of transgenic mice and cell free misfolding assays. However, understanding of the molecular mechanisms responsible for the phenotype associated with individual mutations requires knowledge of the intricacies of protein folding and misfolding at an atomic level. As a result of concomitant improvements in computer technology and in force field approximations of biomolecules, molecular modelling is becoming an increasingly useful tool to investigate protein folding dynamics.
We have recently published work that demonstrates the significant protective effect of a mutation at codon 168 (Pro to Leu) in ovine PrP, based on both in vivo and in vitro data. The molecular effect of this mutation may be to stabilise PrPc, destabilise PrPsc or to regulate interaction with accessory molecules involved in the conformational transition. We have undertaken various studies to attempt to decipher the molecular mechanism(s) responsible and molecular dynamics simulations form an important part of these studies. We will present our recent theoretical calculations aimed at defining how a single mutation can have such a profound effect on PrPsc conversion in multiple species and with multiple TSE strains.
AD A.C. Gill, L. Kirby, Roslin Institute (Edinburgh), Neuropathogenesis Unit, UK
SP englisch
PO Schottland