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A computational study on the efficacy of small molecules as dual inhibitors for β-secretase 1 and acetylcholinesterase as Alzheimer’s disease therapeutics


Patrick Ming, Moustafa T. Gabr

Rubric:Pharmaceutical Sciences


Alzheimer’s disease is characterized by the progressive decline of many cognitive functions that involve numerous parts of the brain. Due to the complex nature and multi-faceted pathogenesis of neurodegenerative diseases, AD’s pathology has been correlated with a loss of cholinergic function as well as the overproduction of Aβ42. Because of this, multitargeted ligands have great potential as therapeutics. In this paper, we assessed the “bindability” of the proteins using various computational methods and online software. Then, we virtually screened through millions of potential small molecules using pharmacophore maps to find potential small molecule candidates. We then used software developed by the Swiss Institute of Bioinformatics (SIB) to both assess the binding energy of the small molecules to the compound (of which all compounds had a ∆G < –7.00 kcal/mol) as well as assess the druggability of the small compounds through their ADME profiles. By the end, we were left with 4 organic compounds that showed the most promise as dual inhibitors. Ranked from most to least promising, they are: ZINC68569271, ZINC41367268, ZINC67202317, ZINC05611209. They all show strong binding affinities for both AChE and BACE1, with the majority of each compound having a Gibbs free energy value of ∆G < –7.00 kcal/mol.


Alzheimer’s Disease
β-secretase 1
Molecular Docking


Patrick Ming, Moustafa T. Gabr





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