A Novel Canonical Dual Global Optimization Computational Approach

Abstract

Many experimental studies have shown that the prion AGAAAAGA palindrome hydrophobic region (113–120) has amyloid fibril forming properties and plays an important role in prion diseases. However, due to the unstable, noncrystalline and insoluble nature of the amyloid fibril, to date structural information on AGAAAAGA region (113–120) has been very limited. This region falls just within the N-terminal unstructured region PrP (1–123) of prion proteins. Traditional X-ray crystallography and NMR spectroscopy experimental methods cannot be used to get its structural information. Under this background, this chapter introduces a novel approach of the canonical dual theory to address the 3D atomic-resolution structure of prion AGAAAAGA amyloid fibrils. The novel and powerful canonical dual computational approach introduced in this chapter is for the molecular modeling of prion AGAAAAGA amyloid fibrils, and that the optimal atomic-resolution structures of prion AGAAAAGA amyloid fibils presented in this chapter are useful for the drive to find treatments for prion diseases in the field of medicinal chemistry. Overall, this chapter presents an important method and provides useful information for treatments of prion diseases.