NR AOZN
AU Stork,M.; Tavan,P.
TI Structural stability of parallel ß-helices studied by molecular dynamics simulations
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-58
PT Konferenz-Poster
AB
The molecular structures of amyloid fibers characterizing neurodegenerative diseases like BSE or Huntington are unknown, because these fibers are large and non-crystalline making them inaccessible to highly resolved structure determination by multidimensional NMR and X-ray crystallography. Recently, both electron diffraction of two-dimensional crystals formed from
building blocks of prion rods and a new interpretation of X-ray diffraction patterns of polyglutamine have pointed towards a common structural motif of amyloid fibers, which is called parallel ß-helices.By MD-simulations we have investigated the structural stability of several variants of such ß-helices in aqueous solution. In particular, we have asked the question, whether there exists a preferred geometry, a preferred number of amino acids per coil (i.e., per ß-helical turn), and whether a minimal number of coils is required for stability. Up to date, our simulations indicate that two coils are less stable than three in triangular 18-membered ß-helices. This turned out to be the case for small fragments of a native ß-helix comprising ten coils and for mpolyglutamine.We also address the stability of ß-helices suggested by Wille et al. (Proc. Natl. Acad. Sci. (USA) 99, 3563, 2002) as models for PrP-Sc.
AD Martina Stork, Paul Tavan, Theoretische Biophysik, BioMolekulare Optik, Sektion Physik, LMU, Germany
SP englisch
PO Deutschland