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...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3312348?pdf=render |
| _version_ | 1819104371650068480 |
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| author | Weng Ieong Tou Calvin Yu-Chian Chen |
| author_facet | Weng Ieong Tou Calvin Yu-Chian Chen |
| author_sort | Weng Ieong Tou |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-22T02:05:18Z |
| format | Article |
| id | doaj.art-305ef604f5eb4941904b87e9f3a66545 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T02:05:18Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-305ef604f5eb4941904b87e9f3a665452022-12-21T18:42:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0173e3372810.1371/journal.pone.0033728In silico investigation of potential SRC kinase ligands from traditional Chinese medicine.Weng Ieong TouCalvin Yu-Chian ChenSrc 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.http://europepmc.org/articles/PMC3312348?pdf=render |
| spellingShingle | Weng Ieong Tou Calvin Yu-Chian Chen In silico investigation of potential SRC kinase ligands from traditional Chinese medicine. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC3312348?pdf=render |
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