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Exploring the Binding Pattern of Geraniol with Acetylcholinesterase through In Silico Docking, Molecular Dynamics Simulation, and In Vitro Enzyme Inhibition Kinetics Studies
| Content Provider | MDPI |
|---|---|
| Author | Iqbal, Danish Khan, M. Salman Waiz, Mohd Rehman, Tabish Alaidarous, Mohammed Jamal, Azfar Alothaim, Abdulaziz S. AlAjmi, Mohamed F. Alshehri, Bader Mohammed Banawas, Saeed Alsaweed, Mohammed Madkhali, Yahya Algarni, Abdulrahman Alsagaby, Suliman A. Alturaiki, Wael |
| Copyright Year | 2021 |
| Description | Acetylcholinesterase (AChE) inhibition is a key element in enhancing cholinergic transmission and subsequently relieving major symptoms of several neurological and neuromuscular disorders. Here, the inhibitory potential of geraniol and its mechanism of inhibition against AChE were elucidated in vitro and validated via an in silico study. Our in vitro enzyme inhibition kinetics results show that at increasing concentrations of geraniol and substrate, Vmax did not change significantly, but Km increased, which indicates that geraniol is a competitive inhibitor against AChE with an $IC_{50}$ value 98.06 ± 3.92 µM. All the parameters of the ADME study revealed that geraniol is an acceptable drug candidate. A docking study showed that the binding energy of geraniol (−5.6 kcal $mol^{−1}$) was lower than that of acetylcholine (−4.1 kcal $mol^{−1}$) with AChE, which exhibited around a 12.58-fold higher binding affinity of geraniol. Furthermore, molecular dynamics simulation revealed that the RMSD of AChE alone or in complex with geraniol fluctuated within acceptable limits throughout the simulation. The mean RMSF value of the complex ensures that the overall conformation of the protein remains conserved. The average values of Rg, MolSA, SASA, and PSA of the complex were 3.16 Å, 204.78, 9.13, and 51.58 $Å^{2}$, respectively. We found that the total SSE of AChE in the complex was 38.84% (α-helix: 26.57% and β-sheets: 12.27%) and remained consistent throughout the simulation. These findings suggest that geraniol remained inside the binding cavity of AChE in a stable conformation. Further in vivo investigation is required to fully characterize the pharmacokinetic properties, optimization of dose administration, and efficacy of this plant-based natural compound. |
| Starting Page | 3533 |
| e-ISSN | 20734409 |
| DOI | 10.3390/cells10123533 |
| Journal | Cells |
| Issue Number | 12 |
| Volume Number | 10 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-12-14 |
| Access Restriction | Open |
| Subject Keyword | Cells Integrative and Complementary Medicine Neurological Disorders Acetylcholinesterase Geraniol Enzyme Inhibition Kinetics Molecular Docking Molecular Dynamics Simulation |
| Content Type | Text |
| Resource Type | Article |
