Compared with the NMR Structure and Dynamics of Humans and Mice

Abstract

The chapter is a straight forward molecular dynamics simulation study of wild-type rabbit prion protein (monomer cellular form) which apparently resists the formation of the scrapie form. The comparison analyses with human and mouse prion proteins done so far show that the rabbit prion protein has a stable structure. The main point is that the enhanced stability of the C-terminal ordered region especially H2 through the D177-R163 salt-bridge formation renders the rabbit prion protein stable. The SB D201-R155 linking H3 and H1 also contributes to the structural stability of rabbit prion protein. The HB H186-R155 partially contributes to the structural stability of rabbit prion protein. Conclusions: Rabbit prion protein was found to own the structural stability, the SBs D177-R163, D201-R155 greatly contribute and the HB H186-R155 partially contributes to this structural stability. These SBs may be important drug targets or they are potentially important drug targets for treating prion diseases. Dima et al. also confirmed this point and pointed out that “correlated mutations that reduce the frustration in the second half of H2 in mammalian prion proteins could inhibit the formation of PrP Sc ” (Dima and Thirumalai, Biophys J 83(3):1268–1280, 2002; Proc Natl Acad Sci U S A 101(43):15335–15340, 2004).