Exploring the Binding Pattern of Geraniol with Acetylcholinesterase through In Silico Docking, Molecular Dynamics
Danish Iqbal1, M Salman Khan2, Mohd Waiz2
1Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah 11952, Saudi Arabia.
Geraniol competitively inhibits acetylcholinesterase (AChE), an enzyme targeted for neurological disorders. This plant-based compound shows promise as a drug candidate, with further in vivo studies needed for efficacy.
Area of Science:
- Biochemistry
- Pharmacology
- Computational Chemistry
Background:
- Acetylcholinesterase (AChE) inhibition is crucial for managing neurological and neuromuscular disorders by enhancing cholinergic transmission.
- Geraniol, a natural compound, was investigated for its potential to inhibit AChE.
Purpose of the Study:
- To elucidate the inhibitory potential and mechanism of geraniol against AChE.
- To validate these findings using in silico methods.
- To assess geraniol's drug-likeness through ADME parameter evaluation.
Main Methods:
- In vitro enzyme kinetics assays were performed to determine the inhibition type and IC50 value.
- In silico studies included docking and molecular dynamics simulations.
- Absorption, Distribution, Metabolism, and Excretion (ADME) parameters were analyzed.
Main Results:
- Geraniol demonstrated competitive inhibition against AChE with an IC50 of 98.06 ± 3.92 µM.
- In silico analysis revealed a higher binding affinity of geraniol to AChE compared to acetylcholine (-5.6 kcal mol-1 vs. -4.1 kcal mol-1).
- Molecular dynamics simulations confirmed the stable binding of geraniol within the AChE active site.
Conclusions:
- Geraniol is a competitive inhibitor of AChE with favorable drug-like properties.
- The compound exhibits significant binding affinity and stable interaction with AChE.
- Further in vivo studies are warranted to confirm pharmacokinetic properties and therapeutic efficacy.
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