Introduction: Apolipoprotein E4 (ApoE) is a major genetic factor for developing Alzheimer’s
disease (AD). It plays a vital role in brain to maintain a constant supply of neuronal lipids for
rapid and dynamic membrane synthesis. Aggregation of beta amyloid plaques (Aβ) and neurofibrillary
tangles in brain are responsible for onset of AD. The current study is designed to predict a drug against
over activity of apoE4. 22 natural compounds (marine, microorganism and plant derivative) were used
in current study.
Methods: These compounds were used as inhibitors to target apoE4 protein activity. Moreover, six synthetic
compounds were docked with target protein to compare and analyze the docking results with
natural compounds. S-Allyl-L-Cysteine, Epicatechin Gallate and Fulvic acid showed highest binding
affinity (-7.1, - 7 and -7 kcal /mol respectively). Analysis of the docked complex showed that Epicatechin
Gallate bonded with Gln156 and Asp35. Furthermore, Fulvic Acid showed hydrogen bonding with
Glu27. Among synthetic compound, Tideglusib had highest binding affinity with target protein but did
not show hydrogen bonding with any amino acid residue. Moreover, a natural compound S-Allyl-LCysteine
also showed highest binding affinity but did not show hydrogen bonding with any amino acid
Results and Conclusion: Our study highlighted Epicatechin Gallate as a potential lead compound on
the basis of binding affinity and hydrogen bonding to inhibit the progression of AD.