Structural Dynamics and Susceptibility of Anti-Alzheimer’s Drugs Donepezil and Galantamine against Human Acetylcholinesterase
نویسندگان
چکیده
Alzheimer’s disease (AD) is a major public health problem worldwide due to an increase in the elderly population. The current pharmacotherapy for early stages of AD mainly dependent on cholinesterase inhibitors. Two most commonly used anti-AD drugs, donepezil (DPZ) and galantamine (GLM), are selective inhibitors human acetylcholinesterase (hAChE). However, inhibitory activity DPZ hAChE was more potent than GLM by ~85 times. To better understand molecular basis differences mode inhibition both dynamics (MD) simulation performed. results showed that active site residues hAChE/DPZ had higher hydrogen bond occupancies as compared hAChE/GLM. Nevertheless, 2 drugs directly formed bonds with catalytic residue H447 hAChE. per-residue free energy decomposition suggested interacted peripheral anionic hAChE, resulting greater binding affinity toward calculation based MM-PBSA MM-GBSA methods indicated van der Waal interactions played predominant role driving force process Moreover, predicted total stronger hAChE/GLM, which consistent well experimental data. We hope our findings provide useful information further design novel inhibitors.
 HIGHLIGHTS
 
 Anti-Alzheimer’s complex were explored MD simulations calculations
 MM-PB(GB)SA-based exhibited favorable galantamine
 rotation during resulted reduction D74 S203
 Waals considered contributor drugs
 GRAPHICAL ABSTRACT
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ژورنال
عنوان ژورنال: Trends in Sciences
سال: 2022
ISSN: ['2774-0226']
DOI: https://doi.org/10.48048/tis.2022.4587