Abstract

COMPARATIVE DOCKING STUDY OF DONEPEZIL AND FATTY ACIDS TARGETING ALZHEIMER'S RECEPTORS 1DX6 AND 3K5F

*Dr. Thomas Kurian and Dr. Rani Sebastian

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Abstract

The binding affinities of a range of ligands, such as the standard Alzheimer's medicine donepezil and natural fatty acids (arachidonic acid, Dihomo-γ-linolenic acid, docosahexaenoic acid (DHA), alphalinolenic acid, and Eicosapentaenoic acid (EPA), towards two Alzheimer's disease-related receptors, 1DX6 and 3K5F, are examined in this study. Different software programs were used for molecular docking simulations: Auto Dock, PyRX, and MZ DOCK. The findings confirmed the sensitivity of the docking tools by consistently showing that Donepezil had the highest binding affinity for both receptors and across all platforms. Particularly when MZ DOCK and PyRX evaluated DHA and EPA, they showed comparatively greater binding energies than other fatty acids among the natural ligands. Interestingly, Auto Dock consistently anticipated that the natural chemicals would bind less strongly than Donepezil. Compared to all-natural ligands, Donepezil had a dramatically greater binding affinity for the 1DX6 receptor (-8.97 kcal/mol with Auto Dock). Likewise, Donepezil showed the highest affinity (-10.9kcal/mol with MZ DOCK) for the 3K5F receptor. PyRX predicted alpha-linolenic acid would interact strongly with 3K5F (-8.5 kcal/mol). These results underscore the need for more research into these natural chemicals' potential as lead molecules or adjunct therapeutics in the setting of Alzheimer's disease (AD), Emphasizing the urgency of the AD problem.

Keywords: Alzheimers, PyRX, MZ DOCK, Auto dock, 1DX6, 3K5F.