アルツハイマー病と認知症のジャーナル オープンアクセス

抽象的な

In silico Identification of novel ApoE4 inhibitor for Alzheimers disease therapy

Muhammad Asif Rasheed

ApoE4 is a major genetic risk factor due to its increase incidence of developing Alzheimer???s disease. The study was designed to predict such compounds that may helpful in designing drug to suppress the over activity of apoE4 protein. 22 natural compounds (marine, microorganism and plant derivative) were used as inhibitors and docked with apoE4 (PDB id 1B68). 6 Synthetic compounds (In clinical trials) were docked with target protein to compare and analyze the docking results with natural compounds. Compounds S-Allyl-L-Cysteine, Epicatechin Gallate and Fulvic Acid show high binding affinity i.e. -7.1, - 7 and -7 respectively. Epicatechin Gallate shows hydrogen bond with Gln156 and Asp35 and Fulvic Acid shows hydrogen bonding with Glu27. In case of synthetic compounds Tideglusib did not show hydrogen bonding with any amino acid residue of ApoE4 but show high binding affinity of -7.2 same as of natural compound S-Allyl-L-Cysteine which show high binding affinity of -7.1 but did not show hydrogen bonding with any amino acid residue. Protein-Protein interactions of apoE4 show physical and functional interaction with related proteins. Our study predict a compound Epicatechin Gallate on the basis of binding affinity and hydrogen bonding with amino acid residue as a potential lead compound which may be used as an inhibitor.