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In Silico Investigation of Potential TRAF6 Inhibitor from Traditional Chinese Medicine against Cancers

It has been indicated that tumor necrosis factor receptor-associated factor-6 (TRAF6) will upregulate the expression of hypoxia-inducible factor-1α (HIF-1α) and promote tumor angiogenesis. TRAF6 proteins can be treated as drug target proteins for a differentiation therapy against cancers. As structu...

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Autores principales: Chen, Kuan-Chung, Lee, Wen-Yuan, Chen, Hsin-Yi, Chen, Calvin Yu-Chian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096009/
https://www.ncbi.nlm.nih.gov/pubmed/25089269
http://dx.doi.org/10.1155/2014/429486
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author Chen, Kuan-Chung
Lee, Wen-Yuan
Chen, Hsin-Yi
Chen, Calvin Yu-Chian
author_facet Chen, Kuan-Chung
Lee, Wen-Yuan
Chen, Hsin-Yi
Chen, Calvin Yu-Chian
author_sort Chen, Kuan-Chung
collection PubMed
description It has been indicated that tumor necrosis factor receptor-associated factor-6 (TRAF6) will upregulate the expression of hypoxia-inducible factor-1α (HIF-1α) and promote tumor angiogenesis. TRAF6 proteins can be treated as drug target proteins for a differentiation therapy against cancers. As structural disordered disposition in the protein may induce the side-effect and reduce the occupancy for ligand to bind with target protein, PONDR-Fit protocol was performed to predict the disordered disposition in TRAF6 protein before virtual screening. TCM compounds from the TCM Database@Taiwan were employed for virtual screening to identify potent compounds as lead compounds of TRAF6 inhibitor. After virtual screening, the MD simulation was performed to validate the stability of interactions between TRAF6 proteins and each ligand. The top TCM compounds, tryptophan, diiodotyrosine, and saussureamine C, extracted from Saussurea lappa Clarke, Bos taurus domesticus Gmelin, and Lycium chinense Mill., have higher binding affinities with target protein in docking simulation. However, the docking pose of TRAF6 protein with tryptophan is not stable under dynamic condition. For the other two TCM candidates, diiodotyrosine and saussureamine C maintain the similar docking poses under dynamic conditions. Hence, we propose the TCM compounds, diiodotyrosine and saussureamine C, as potential candidates as lead compounds for further study in drug development process with the TRAF6 protein against cancer.
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spelling pubmed-40960092014-08-03 In Silico Investigation of Potential TRAF6 Inhibitor from Traditional Chinese Medicine against Cancers Chen, Kuan-Chung Lee, Wen-Yuan Chen, Hsin-Yi Chen, Calvin Yu-Chian Biomed Res Int Research Article It has been indicated that tumor necrosis factor receptor-associated factor-6 (TRAF6) will upregulate the expression of hypoxia-inducible factor-1α (HIF-1α) and promote tumor angiogenesis. TRAF6 proteins can be treated as drug target proteins for a differentiation therapy against cancers. As structural disordered disposition in the protein may induce the side-effect and reduce the occupancy for ligand to bind with target protein, PONDR-Fit protocol was performed to predict the disordered disposition in TRAF6 protein before virtual screening. TCM compounds from the TCM Database@Taiwan were employed for virtual screening to identify potent compounds as lead compounds of TRAF6 inhibitor. After virtual screening, the MD simulation was performed to validate the stability of interactions between TRAF6 proteins and each ligand. The top TCM compounds, tryptophan, diiodotyrosine, and saussureamine C, extracted from Saussurea lappa Clarke, Bos taurus domesticus Gmelin, and Lycium chinense Mill., have higher binding affinities with target protein in docking simulation. However, the docking pose of TRAF6 protein with tryptophan is not stable under dynamic condition. For the other two TCM candidates, diiodotyrosine and saussureamine C maintain the similar docking poses under dynamic conditions. Hence, we propose the TCM compounds, diiodotyrosine and saussureamine C, as potential candidates as lead compounds for further study in drug development process with the TRAF6 protein against cancer. Hindawi Publishing Corporation 2014 2014-06-25 /pmc/articles/PMC4096009/ /pubmed/25089269 http://dx.doi.org/10.1155/2014/429486 Text en Copyright © 2014 Kuan-Chung Chen et al. https://creativecommons.org/licenses/by/3.0/ 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.
spellingShingle Research Article
Chen, Kuan-Chung
Lee, Wen-Yuan
Chen, Hsin-Yi
Chen, Calvin Yu-Chian
In Silico Investigation of Potential TRAF6 Inhibitor from Traditional Chinese Medicine against Cancers
title In Silico Investigation of Potential TRAF6 Inhibitor from Traditional Chinese Medicine against Cancers
title_full In Silico Investigation of Potential TRAF6 Inhibitor from Traditional Chinese Medicine against Cancers
title_fullStr In Silico Investigation of Potential TRAF6 Inhibitor from Traditional Chinese Medicine against Cancers
title_full_unstemmed In Silico Investigation of Potential TRAF6 Inhibitor from Traditional Chinese Medicine against Cancers
title_short In Silico Investigation of Potential TRAF6 Inhibitor from Traditional Chinese Medicine against Cancers
title_sort in silico investigation of potential traf6 inhibitor from traditional chinese medicine against cancers
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096009/
https://www.ncbi.nlm.nih.gov/pubmed/25089269
http://dx.doi.org/10.1155/2014/429486
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