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Soyasapogenol-B as a Potential Multitarget Therapeutic Agent for Neurodegenerative Disorders: Molecular Docking and Dynamics Study

Neurodegenerative disorders involve various pathophysiological pathways, and finding a solution for these issues is still an uphill task for the scientific community. In the present study, a combination of molecular docking and dynamics approaches was applied to target different pathways leading to...

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Autores principales: Iqbal, Danish, Rizvi, Syed Mohd Danish, Rehman, Md Tabish, Khan, M. Salman, Bin Dukhyil, Abdulaziz, AlAjmi, Mohamed F., Alshehri, Bader Mohammed, Banawas, Saeed, Zia, Qamar, Alsaweed, Mohammed, Madkhali, Yahya, Alsagaby, Suliman A., Alturaiki, Wael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9141571/
https://www.ncbi.nlm.nih.gov/pubmed/35626478
http://dx.doi.org/10.3390/e24050593
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author Iqbal, Danish
Rizvi, Syed Mohd Danish
Rehman, Md Tabish
Khan, M. Salman
Bin Dukhyil, Abdulaziz
AlAjmi, Mohamed F.
Alshehri, Bader Mohammed
Banawas, Saeed
Zia, Qamar
Alsaweed, Mohammed
Madkhali, Yahya
Alsagaby, Suliman A.
Alturaiki, Wael
author_facet Iqbal, Danish
Rizvi, Syed Mohd Danish
Rehman, Md Tabish
Khan, M. Salman
Bin Dukhyil, Abdulaziz
AlAjmi, Mohamed F.
Alshehri, Bader Mohammed
Banawas, Saeed
Zia, Qamar
Alsaweed, Mohammed
Madkhali, Yahya
Alsagaby, Suliman A.
Alturaiki, Wael
author_sort Iqbal, Danish
collection PubMed
description Neurodegenerative disorders involve various pathophysiological pathways, and finding a solution for these issues is still an uphill task for the scientific community. In the present study, a combination of molecular docking and dynamics approaches was applied to target different pathways leading to neurodegenerative disorders such as Alzheimer’s disease. Initially, abrineurin natural inducers were screened using physicochemical properties and toxicity assessment. Out of five screened compounds, a pentacyclic triterpenoid, i.e., Soyasapogenol B appeared to be the most promising after molecular docking and simulation analysis. Soyasapogenol B showed low TPSA (60.69), high absorption (82.6%), no Lipinski rule violation, and no toxicity. Docking interaction analysis revealed that Soyasapogenol B bound effectively to all of the targeted proteins (AChE, BuChE MAO-A, MAO-B, GSK3β, and NMDA), in contrast to other screened abrineurin natural inducers and inhibitors. Importantly, Soyasapogenol B bound to active site residues of the targeted proteins in a similar pattern to the native ligand inhibitor. Further, 100 ns molecular dynamics simulations analysis showed that Soyasapogenol B formed stable complexes against all of the targeted proteins. RMSD analysis showed that the Soyasapogenol B–protein complex exhibited average RMSD values of 1.94 Å, 2.11 Å, 5.07 Å, 2.56 Å, 3.83 Å and 4.07 Å. Furthermore, the RMSF analysis and secondary structure analysis also indicated the stability of the Soyasapogenol B–protein complexes.
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spelling pubmed-91415712022-05-28 Soyasapogenol-B as a Potential Multitarget Therapeutic Agent for Neurodegenerative Disorders: Molecular Docking and Dynamics Study Iqbal, Danish Rizvi, Syed Mohd Danish Rehman, Md Tabish Khan, M. Salman Bin Dukhyil, Abdulaziz AlAjmi, Mohamed F. Alshehri, Bader Mohammed Banawas, Saeed Zia, Qamar Alsaweed, Mohammed Madkhali, Yahya Alsagaby, Suliman A. Alturaiki, Wael Entropy (Basel) Article Neurodegenerative disorders involve various pathophysiological pathways, and finding a solution for these issues is still an uphill task for the scientific community. In the present study, a combination of molecular docking and dynamics approaches was applied to target different pathways leading to neurodegenerative disorders such as Alzheimer’s disease. Initially, abrineurin natural inducers were screened using physicochemical properties and toxicity assessment. Out of five screened compounds, a pentacyclic triterpenoid, i.e., Soyasapogenol B appeared to be the most promising after molecular docking and simulation analysis. Soyasapogenol B showed low TPSA (60.69), high absorption (82.6%), no Lipinski rule violation, and no toxicity. Docking interaction analysis revealed that Soyasapogenol B bound effectively to all of the targeted proteins (AChE, BuChE MAO-A, MAO-B, GSK3β, and NMDA), in contrast to other screened abrineurin natural inducers and inhibitors. Importantly, Soyasapogenol B bound to active site residues of the targeted proteins in a similar pattern to the native ligand inhibitor. Further, 100 ns molecular dynamics simulations analysis showed that Soyasapogenol B formed stable complexes against all of the targeted proteins. RMSD analysis showed that the Soyasapogenol B–protein complex exhibited average RMSD values of 1.94 Å, 2.11 Å, 5.07 Å, 2.56 Å, 3.83 Å and 4.07 Å. Furthermore, the RMSF analysis and secondary structure analysis also indicated the stability of the Soyasapogenol B–protein complexes. MDPI 2022-04-23 /pmc/articles/PMC9141571/ /pubmed/35626478 http://dx.doi.org/10.3390/e24050593 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Iqbal, Danish
Rizvi, Syed Mohd Danish
Rehman, Md Tabish
Khan, M. Salman
Bin Dukhyil, Abdulaziz
AlAjmi, Mohamed F.
Alshehri, Bader Mohammed
Banawas, Saeed
Zia, Qamar
Alsaweed, Mohammed
Madkhali, Yahya
Alsagaby, Suliman A.
Alturaiki, Wael
Soyasapogenol-B as a Potential Multitarget Therapeutic Agent for Neurodegenerative Disorders: Molecular Docking and Dynamics Study
title Soyasapogenol-B as a Potential Multitarget Therapeutic Agent for Neurodegenerative Disorders: Molecular Docking and Dynamics Study
title_full Soyasapogenol-B as a Potential Multitarget Therapeutic Agent for Neurodegenerative Disorders: Molecular Docking and Dynamics Study
title_fullStr Soyasapogenol-B as a Potential Multitarget Therapeutic Agent for Neurodegenerative Disorders: Molecular Docking and Dynamics Study
title_full_unstemmed Soyasapogenol-B as a Potential Multitarget Therapeutic Agent for Neurodegenerative Disorders: Molecular Docking and Dynamics Study
title_short Soyasapogenol-B as a Potential Multitarget Therapeutic Agent for Neurodegenerative Disorders: Molecular Docking and Dynamics Study
title_sort soyasapogenol-b as a potential multitarget therapeutic agent for neurodegenerative disorders: molecular docking and dynamics study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9141571/
https://www.ncbi.nlm.nih.gov/pubmed/35626478
http://dx.doi.org/10.3390/e24050593
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