Dynamic simulation of the mouse prion protein.

Conformational flexibility in the prion protein is believed to play a role in prion diseases. Here we examine the dynamic structure of the mouse cellular prion protein using two one-nanosecond molecular dynamics simulations from different initial conditions. The two simulations produce similar results. The overall structure remains close to that determined by nmr spectroscopy, with small deviations arising from loop fluctuation and slight changes in the relative helix positions. The sequence dependence of the fluctuation magnitudes is similar to the variation between the nmr-derived structure solutions. In both simulations, the N-terminal region of the protein forms a short, two-stranded beta-sheet, to which a third strand joins after approximately 100 ps. The additional strand may reflect nucleative properties of the beta-sheet required for disease-related prion conformational change. Copyright 2000 John Wiley & Sons, Inc.