Version 1
: Received: 1 September 2024 / Approved: 2 September 2024 / Online: 2 September 2024 (23:31:10 CEST)
How to cite:
Rakesh, U. L.; Anil Kumar, G.; Panneerselvam, T.; Pavadai, P.; Veerachamy, S.; Palanisamy, P.; Bandral, S. K.; Alagarsamy*, S. K. K.; Kunjiappan, S. Molecular Modeling Tools Used for the Prediction of Amyloid-β Fibrils Disaggregating Molecules from Plant Sources. Preprints2024, 2024090119. https://doi.org/10.20944/preprints202409.0119.v1
Rakesh, U. L.; Anil Kumar, G.; Panneerselvam, T.; Pavadai, P.; Veerachamy, S.; Palanisamy, P.; Bandral, S. K.; Alagarsamy*, S. K. K.; Kunjiappan, S. Molecular Modeling Tools Used for the Prediction of Amyloid-β Fibrils Disaggregating Molecules from Plant Sources. Preprints 2024, 2024090119. https://doi.org/10.20944/preprints202409.0119.v1
Rakesh, U. L.; Anil Kumar, G.; Panneerselvam, T.; Pavadai, P.; Veerachamy, S.; Palanisamy, P.; Bandral, S. K.; Alagarsamy*, S. K. K.; Kunjiappan, S. Molecular Modeling Tools Used for the Prediction of Amyloid-β Fibrils Disaggregating Molecules from Plant Sources. Preprints2024, 2024090119. https://doi.org/10.20944/preprints202409.0119.v1
APA Style
Rakesh, U. L., Anil Kumar, G., Panneerselvam, T., Pavadai, P., Veerachamy, S., Palanisamy, P., Bandral, S. K., Alagarsamy*, S. K. K., & Kunjiappan, S. (2024). Molecular Modeling Tools Used for the Prediction of Amyloid-β Fibrils Disaggregating Molecules from Plant Sources. Preprints. https://doi.org/10.20944/preprints202409.0119.v1
Chicago/Turabian Style
Rakesh, U. L., Santhana Krishna Kumar Alagarsamy* and Selvaraj Kunjiappan. 2024 "Molecular Modeling Tools Used for the Prediction of Amyloid-β Fibrils Disaggregating Molecules from Plant Sources" Preprints. https://doi.org/10.20944/preprints202409.0119.v1
Abstract
The defining characteristic of Alzheimer's disease (AD) is the aberrant deposition of pathogenic proteins, particularly a massive build-up of amyloid-β peptides, specifically in the brain. Amy-loid-β aggregation is neurotoxic and ultimately results in dysfunction of the nervous system. The present investigation aims to predict potential amyloid-β fibrils disaggregating molecules from plant sources through molecular modeling techniques, this appears to be a very promising and appealing treatment philosophy. Here, 500 flavonoids from various plants were considered, ini-tially undergoing ADME studies to screen molecules that could cross the blood-brain barrier. Later, potential Amyloid-β-disaggregating molecules were identified by molecular docking and dynamics (MD) simulation studies. Five molecules, prenylmethoxy flavonol (-7.3 kcal×mol-1), isopentenyl flavonol (-7.3 kcal×mol-1), 7,3'-Dihydroxyflavone (-7.2 kcal×mol-1), 7-Hydroxy-5-methyl-4'-methoxyflavone (-7.2 kcal×mol-1), 8-hydroxy-7-methoxyflavone (-7 kcal×mol-1) showed higher binding affinity score against Alzheimer's Aβ (1-42) fibrils, these are very close to the standard drug (Donepezil) (-7.90 kcal×mol-1). Further, the MD simulation studies established the intermolecular interaction and stability of the five selected ligands-Amyloid-β oligomer protein complexes. These results suggest that the chosen five flavonoid molecules could be used as possible agents to disaggregate amyloid-β fibrils; however, more in vitro and in vivo investigations are required to verify the therapeutic effectiveness.
Biology and Life Sciences, Cell and Developmental Biology
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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