Prediction of Novel Insecticides for Malaria Prevention: Virtual Screening and Molecular Dynamics of AgAChE Inhibitors
Abstract
1. Introduction
2. Results
2.1. Ligand-Based Pharmacophore Modeling and Virtual Screening of PubChem Databse
2.2. ADMET Properties
2.3. Molecular Dynamics Simulations of AgAChE-Ligands Complexes
3. Discussion
4. Materials and Methods
4.1. Ligand-Based Pharmacophore Modeling and Virtual Screening
4.2. Molecular Docking
4.3. In Silico ADMET Prediction
4.4. Molecular Dynamics Simulations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AChE | Acetylcholinesterase |
AgAChE | Anopheles gambiae Acetylcholinesterase |
DFK | Difluoromethyl ketone |
ADMET | Absorption, Distribution, Metabolism, Excretion and Toxicity |
WHO | World Health Organization |
OP | Organophosphate |
ACh | Acetylcholine |
AChR | ACh receptor |
hAChE | human Acetylcholinesterase |
RMSD | Root Mean Square Deviation |
NVT | Constant set of particle numbers, volume, and temperature |
NPT | Constant set of particle number, pressure, and temperature |
PME | Particle Mesh Ewald |
RMSF | Root Mean Square Fluctuation |
MD | Molecular dynamics |
PLIP | Protein-Ligand Interaction Profiler |
MW | Molecular weight |
RB | Rotatable bonds |
HBA | Hydrogen bond acceptor |
HBD | Hydrogen bond donor |
HP | Hepatotoxicity |
SS | Skin sensitization |
MM/PBSA | Molecular Mechanics Poisson–Boltzmann Surface Area |
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ID | MW 1 | MLogP | 2 RB | 3 HBA | 4 HBD | AMES | 5 HP | 6 SS |
---|---|---|---|---|---|---|---|---|
DFK | 218.24 | 1.44 | 5 | 4 | 1 | No | No | Yes |
PC6 | 414.37 | 2.32 | 5 | 8 | 2 | No | Yes | No |
Complex | ΔGMM/PBSA | SD 1 |
---|---|---|
AgAChE1-DFK | −26.38 | 4.02 |
AgAChE1-PC6 | −29.89 | 7.15 |
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Souza, F.F.; Vilachã, J.F.; Campos, O.S.; de Paula, H. Prediction of Novel Insecticides for Malaria Prevention: Virtual Screening and Molecular Dynamics of AgAChE Inhibitors. Drugs Drug Candidates 2025, 4, 41. https://doi.org/10.3390/ddc4030041
Souza FF, Vilachã JF, Campos OS, de Paula H. Prediction of Novel Insecticides for Malaria Prevention: Virtual Screening and Molecular Dynamics of AgAChE Inhibitors. Drugs and Drug Candidates. 2025; 4(3):41. https://doi.org/10.3390/ddc4030041
Chicago/Turabian StyleSouza, Fernanda F., Juliana F. Vilachã, Othon S. Campos, and Heberth de Paula. 2025. "Prediction of Novel Insecticides for Malaria Prevention: Virtual Screening and Molecular Dynamics of AgAChE Inhibitors" Drugs and Drug Candidates 4, no. 3: 41. https://doi.org/10.3390/ddc4030041
APA StyleSouza, F. F., Vilachã, J. F., Campos, O. S., & de Paula, H. (2025). Prediction of Novel Insecticides for Malaria Prevention: Virtual Screening and Molecular Dynamics of AgAChE Inhibitors. Drugs and Drug Candidates, 4(3), 41. https://doi.org/10.3390/ddc4030041