IP Indian Journal of Neurosciences 2020;6(3):174–182 Content available at: https://www.ipinnovative.com/open-access-journals IP Indian Journal of Neurosciences Journal homepage: www.ipinnovative.com Original Research Article Spectroscopic and insilico Studies of Aβ (1-16) on Copper induced conformational changes in Poly (dG-dC). Poly ( dG-dC) [Poly(GC)] DNA sequence: Implications in Alzheimer’s disease Govindaraju M 1, *, Jagadeesh Kumar D 2 , Priya Narayan 2 , K R S Sambasiva Rao 3 , K S Rao 4 1 Dept. of Molecular Biophysics Unit, Indian Institute of Science, Bengaluru, Karnataka, India 2 Dept. of Bio-Technology, Sir M. Visvesvaraya Institute of Technology, Bengaluru, Karnataka, India 3 Dept. of Biotechnology, Mizoram University (A Central University), Aizawl, Mizoram, India 4 Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Clayton, City of Knowledge, Panama ARTICLE INFO Article history: Received 11-08-2020 Accepted 19-08-2020 Available online 18-09-2020 Keywords: Alzheimer’s disease DNA Copper Circular Dichroism Molecular Docking 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 (Aβ ) 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 Aβ 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 Aβ -copper complexes with DNA via hydrogen bond formed between Guanine-Cytosine (GC) pairs. This work gives clues as to how copper Aβ complex modulates DNA conformations which attributes to the stability. © 2020 Published by Innovative Publication. This is an open access article under the CC BY-NC license (https://creativecommons.org/licenses/by-nc/4.0/) 1. Introduction It has been reported that in cells the predominant DNA conformation is in its B form (Right handed), which is known to play a pivotal role in cellular processes. These include carrying of genetic information thereby playing a role in Protein synthesis. 1 DNA molecule is constantly insulted by several chemicals, metals, and various environmental factors and studies including our group have revealed that metals are capable of interacting with proteins and DNA causing changes in the structure and oxidative deterioration. Different conformations of DNA are * Corresponding author. E-mail address: govindaraja@iisc.ac.in (Govindaraju M). known to exist as B, Z, C and ψ DNA. It is also known from literature that in these different conformations, the double helical geometry, major and minor groove depth and width are varied. 2 The promoter regions are GC rich and over- represented in the eukaryotic genome that forms hairpin secondary structures, and dinucleotide repeats which are shown to be unstable and polymorphic. 3,4 The Poly (GC) sequence are unique class of repeats with alternating purines and pyrimidines form secondary structures, particularly hairpin loops that alter DNA replication and repair. 5 Under specific conditions, the Poly (GC)) adopts a Z DNA conformation (left handed) indicating its several roles in cellular processes. 6–10 and lead to different neurological disorders lead Alzheimer’s disease (AD) and Huntington https://doi.org/10.18231/j.ijn.2020.036 2581-8236/© 2020 Innovative Publication, All rights reserved. 174