An ab initio MO study on the characteristics in the amino acid sequence of PrPsc

Abstract

Prion protein is known as a cause of the prion diseases: BSE, CJD, scrapie, and so on. It is also considered that a structural change from PrPc to PrPSc may cause the diseases, although the three-dimensional structure of PrPSc is not known yet. It is speculated that PrPSc has a structure of left-handed parallel beta helix. In that helix, several triangular rungs are stacked, in which around 18 amino acids are included. In this study, we focus on the origin of the stability of a left-handed parallel beta helix. We estimate the stability of the helix as a sum of the backbone conformational energy, the backbone hydrogen bonding energy, the side chain hydrogen bonding energy and the side chain van der Waals interaction energy. To estimate the backbone conformational energy, we calculated the phi-psi map of alanine model molecule by optimizing all other geometrical parameters. It was found that the backbone conformational energy of a left-handed parallel beta helix is lower than that of an alpha helix. We also calculated the van der Waals interaction energy between the hydrophobic amino acid residues. We found that the van der Waals interaction energy between two rungs is about -10kcal/mol: it plays an important role in forming the beta helix structure.