NR AXIO
AU Baillod,P.; Colombo,M.C.; Tavernelli,I.; Röthlisberger,U.
TI A Replica-Exchange Molecular Dynamics Study of Prion Misfolding Pathways and ß-rich Folds
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Protein Misfolding P01.75
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB Prion diseases are believed to be associated with a rare misfold leading from the cellular, monomeric, soluble, ß-helical PrPc isoform to a pathogenic, aggregated, insoluble, ß-rich PrPsc isoform of unknown structure. The goal of the present simulations is to scan the conformational space available to the PrP monomer via extensive enhanced sampling provided by protein-energy based replica-exchange molecular dynamics. The misfolding free energy surface is characterized as a function of the radius of gyration and of the fraction of native contacts. 1.3% of the conformations sampled display an enhanced ß content (>= 19 residues). A new clustering algorithm is applied to sort the structures of this pool in function of the topology of their ß-contacts. 7 major ß-rich folds are thus identified and analysed in regard to their simulation transition temperatures (folds exclusively present at low and/or high temperature) and abundance. Different in-vitro misfolding experiments involving soluble PrP ß-oligomers as well as PrPsc are reviewed in regard to putative monomeric precursors underlying one or several of the folds identified.
AD P. Baillod, M.C. Colombo, I. Tavernelli, U. Rothlisberger, Ecole Polytechnique, Laboratoire de Chimie et de Biochimie Computatione, Switzerland
SP englisch
PO Schottland