Structural analysis of the AICD central 12 residue peptide stretch and its interactions with metals and polyphenols, as a potential drug target for AD

Abstract

Structural analysis of the central 12 residue stretch of Amyloid precursor protein Intracellular Domain (AICD16-27: T-S-I-H-H-G-V-V-E-V-D-A) was carried out by NMR and homology modeling. Further, metal and polyphenol interactions were also carried out for these 12 residues stretch, as it contains two critical Histidine residues, which were observed to be perturbed via NMR. A full length 57 residues AICD model was generated via computational methods, to ascertain its overall conformation, as the entire structure was unavailable. An overlay of this AICD entire model with the full length Aβ-42 structure matched well, implying similar properties. Docking studies with metals and polyphenols indicated involvement of the key Histidine residues highlighting their roles towards neurodegeneration and AD pathophysiology. Communicated by Ramaswamy H. Sarma