  Mouse prion protein PrP106-126 is a peptide corresponding to the residues
107-127 of human prion protein. It has been shown that PrP106-126 can reproduce
the main neuropathological features of prionrelated transmissible spongiform
encephalopathies and can form amyloid-like fibrils in vitro. The conformational
characteristics of PrP106-126 fibril have been investigated by electron
microscopy, CD spectroscopy, NMR and molecular dynamics simulations. Recent
researches have found out that PrP106-126 in water assumes a stable structure
consisting of two parallel beta-sheets that are tightly packed against each
other. In this work we perform molecular dynamics simulation to reveal the
elongation mechanism of PrP106-126 fibril. Influenced by the edge strands of
the fibril which already adopt beta-sheets conformation, single PrP106-126
peptide forms beta-structure and becomes a new element of the fibril. Under
acidic condition, single PrP106-126 peptide adopts a much larger variety of
conformations than it does under neural condition, which makes a peptide easier
to be influenced by the edge strands of the fibril. However, acidic condition
dose not largely affect the stability of PrP106-126 peptide fibril. Thus, the
speed of fibril elongation can be dramatically increased by lowering the pH
value of the solution. The pH value was adjusted by either changing the
protonation state of the residues or adding hydronium ions (acidic solution) or
hydroxyl ions (alkaline solution). The differences between these two approaches
are analyzed here.
