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In Silico Investigation of Potential Src Kinase Ligands from Traditional Chinese Medicine
Src kinase is an attractive target for drug development based on its established relationship with cancer and possible link to hypertension. The suitability of traditional Chinese medicine (TCM) compounds as potential drug ligands for further biological evaluation was investigated using structure-ba...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3312348/ https://www.ncbi.nlm.nih.gov/pubmed/22470466 http://dx.doi.org/10.1371/journal.pone.0033728 |
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author | Tou, Weng Ieong Chen, Calvin Yu-Chian |
author_facet | Tou, Weng Ieong Chen, Calvin Yu-Chian |
author_sort | Tou, Weng Ieong |
collection | PubMed |
description | Src kinase is an attractive target for drug development based on its established relationship with cancer and possible link to hypertension. The suitability of traditional Chinese medicine (TCM) compounds as potential drug ligands for further biological evaluation was investigated using structure-based, ligand-based, and molecular dynamics (MD) analysis. Isopraeroside IV, 9alpha-hydroxyfraxinellone-9-O-beta-D-glucoside (9HFG) and aurantiamide were the top three TCM candidates identified from docking. Hydrogen bonds and hydrophobic interactions were the primary forces governing docking stability. Their stability with Src kinase under a dynamic state was further validated through MD and torsion angle analysis. Complexes formed by TCM candidates have lower total energy estimates than the control Sacaratinib. Four quantitative-structural activity relationship (QSAR) in silico verifications consistently suggested that the TCM candidates have bioactive properties. Docking conformations of 9HFG and aurantiamide in the Src kinase ATP binding site suggest potential inhibitor-like characteristics, including competitive binding at the ATP binding site (Lys295) and stabilization of the catalytic cleft integrity. The TCM candidates have significantly lower ligand internal energies and are estimated to form more stable complexes with Src kinase than Saracatinib. Structure-based and ligand-based analysis support the drug-like potential of 9HFG and aurantiamide and binding mechanisms reveal the tendency of these two candidates to compete for the ATP binding site. |
format | Online Article Text |
id | pubmed-3312348 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33123482012-04-02 In Silico Investigation of Potential Src Kinase Ligands from Traditional Chinese Medicine Tou, Weng Ieong Chen, Calvin Yu-Chian PLoS One Research Article Src kinase is an attractive target for drug development based on its established relationship with cancer and possible link to hypertension. The suitability of traditional Chinese medicine (TCM) compounds as potential drug ligands for further biological evaluation was investigated using structure-based, ligand-based, and molecular dynamics (MD) analysis. Isopraeroside IV, 9alpha-hydroxyfraxinellone-9-O-beta-D-glucoside (9HFG) and aurantiamide were the top three TCM candidates identified from docking. Hydrogen bonds and hydrophobic interactions were the primary forces governing docking stability. Their stability with Src kinase under a dynamic state was further validated through MD and torsion angle analysis. Complexes formed by TCM candidates have lower total energy estimates than the control Sacaratinib. Four quantitative-structural activity relationship (QSAR) in silico verifications consistently suggested that the TCM candidates have bioactive properties. Docking conformations of 9HFG and aurantiamide in the Src kinase ATP binding site suggest potential inhibitor-like characteristics, including competitive binding at the ATP binding site (Lys295) and stabilization of the catalytic cleft integrity. The TCM candidates have significantly lower ligand internal energies and are estimated to form more stable complexes with Src kinase than Saracatinib. Structure-based and ligand-based analysis support the drug-like potential of 9HFG and aurantiamide and binding mechanisms reveal the tendency of these two candidates to compete for the ATP binding site. Public Library of Science 2012-03-21 /pmc/articles/PMC3312348/ /pubmed/22470466 http://dx.doi.org/10.1371/journal.pone.0033728 Text en Tou, Chen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Tou, Weng Ieong Chen, Calvin Yu-Chian In Silico Investigation of Potential Src Kinase Ligands from Traditional Chinese Medicine |
title |
In Silico Investigation of Potential Src Kinase Ligands from Traditional Chinese Medicine |
title_full |
In Silico Investigation of Potential Src Kinase Ligands from Traditional Chinese Medicine |
title_fullStr |
In Silico Investigation of Potential Src Kinase Ligands from Traditional Chinese Medicine |
title_full_unstemmed |
In Silico Investigation of Potential Src Kinase Ligands from Traditional Chinese Medicine |
title_short |
In Silico Investigation of Potential Src Kinase Ligands from Traditional Chinese Medicine |
title_sort | in silico investigation of potential src kinase ligands from traditional chinese medicine |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3312348/ https://www.ncbi.nlm.nih.gov/pubmed/22470466 http://dx.doi.org/10.1371/journal.pone.0033728 |
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