Spectroscopic and insilico Studies of Ab (1-16) on Copper induced conformational changes in Poly (dG-dC). Poly ( dG-dC) [Poly(GC)] DNA sequence: Implications in Alzheimer’s disease

Abstract

DNA molecules are dynamic and play a crucial role in life processes. DNA is polymorphic and flexible having the ability to undergo structural changes depending on the environment. The structural property and stability of DNA are very important for cellular functions, and are involved in normal functioning of processes like replication, repair of DNA and protein synthesis processes. Metals like Fe and Cu are known to play a crucial role in brain functioning and deviations in concentration from the normal are often recognized as symptoms of malfunctions or disease. The effect of copper(Cu) and amyloid peptide (Ab ) on DNA in the brain has been considered very important due to their role in oxidative DNA damage, structural changes of the Amyloid peptide and are the etiological factors for neurodegenerative diseases. In the current investigation, changes in conformation of Poly (GC) sequence DNA induced by copper and Ab 1-16 is studied using Circular Dichroism (CD). CD studies have shown the shift in conformation of DNA, from B form to an altered B-, and C-DNA conformation. The CD studies were substantiated by Molecular docking confirms that the Ab -copper complexes with DNA via hydrogen bond formed between Guanine-Cytosine (GC) pairs. This work gives clues as to how copper Ab complex modulates DNA conformations which attributes to the stability. Keywords: Alzheimer’s disease, DNA, Copper, Circular Dichroism, Molecular Docking.