Abstract:
Alzheimer’s Disease (AD) is a neurodegenerative disorder and is a form of dementia. The plague formed due to amyloid beta fibrillation is one of the characteristics in causing the disease. In the disease condition Aβ interacts with number of proteins and one of them is Prion protein. This interaction causes the Long Term Potentiation (LTP) inhibition in brain hippocampus region and also early development of AD. The research investigates the in silico analysis of proteins such as Aβ42 and Prion protein interaction in AD. Much of the experimental work is done to study their interaction but the aim of this study was to study their interaction computationally. In this paper, the interaction study was conducted between two proteins i.e. Aβ42 and PrP involve in Alzheimer’s disease using LigPlot+ software. For protein-protein docking GRAMM-X web server is used and for protein-ligand docking PyRx software is used. The LigPlot+ software was used to analyze their interaction. The proteins Post Translational Modifications (PTM) sites were also studied using NetPhos web server. The RNA binding sites were also predicted using KYG: RNA server. The result of LigPlot+ shows that Aβ42 interacts with PrP through three hydrogen bonds. The Aβ42 residues involve in hydrogen bonds are Leu34, Ser26, Ala30 and the PrP residues involve in hydrogen bonds are Ile138, Arg220, and Ser135. After this the Aβ42 is docked with anti-Alzheimer’s drugs such as Aricept, Exelon, Namenda and Razadyne. The ligand docked Aβ42 was then interacted with PrP and it showed low affinity with Aβ42. All the four drugs showed same effect as in all the scenarios the Aβ42 showed hydrogen bond interaction at only one site i.e. Aβ42 residue His14 bonds with PrP residue Leu130. This is because all the four drugs have same mechanism of action. From this it is concluded that in Alzheimer’s disease PrP showed affinity for Aβ42 but after the Aβ42 is treated with anti-Alzheimer drugs the affinity of PrP to Aβ42 became low.
