Insight into molecular dynamics simulation of BRAF(V600E) and potent novel inhibitors for malignant melanoma

Insight into molecular dynamics simulation of BRAF(V600E) and potent novel inhibitors for malignant melanoma

Hsin-Chieh Tang,1 Yu-Chian Chen1–3 1Department of Biomedical Informatics, Asia University, Taichung, Taiwan; 2Human Genetic Center, Department of Medical Research, 3Research Center for Chinese Medicine and Acupuncture, China Medical University Hospital, Taichung, Taiwan Abstract: BRAF in...

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Autores principales: Tang HC, Chen YC
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2015
Materias:
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/f5f7ebac0d9e4819a3f4cad2e2d2c151
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spelling oai:doaj.org-article:f5f7ebac0d9e4819a3f4cad2e2d2c1512021-12-02T05:14:27ZInsight into molecular dynamics simulation of BRAF(V600E) and potent novel inhibitors for malignant melanoma1178-2013https://doaj.org/article/f5f7ebac0d9e4819a3f4cad2e2d2c1512015-04-01T00:00:00Zhttp://www.dovepress.com/insight-into-molecular-dynamics-simulation-ofnbspbrafv600e-and-potent--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Hsin-Chieh Tang,1 Yu-Chian Chen1–3 1Department of Biomedical Informatics, Asia University, Taichung, Taiwan; 2Human Genetic Center, Department of Medical Research, 3Research Center for Chinese Medicine and Acupuncture, China Medical University Hospital, Taichung, Taiwan Abstract: BRAF inhibitors have changed the standard therapeutic protocol for advanced or metastatic melanoma which harbored notorious BRAF(V600E) single mutation. However, drug resistance to BRAF inhibitors happens just like other cancer treatment. In this study, we constructed the ideal BRAF(V600E)-modeled structure through homology modeling and introduced the method of structure-based docking or virtual screening from the large compound database. Through certain methods of molecular dynamics simulation, we realized that BRAF(V600E) had quite prominent difference of molecular character or structural variation from the wild-type BRAF protein. It might confer the metamorphic character of advanced melanoma for the patients who harbored BRAF(V600E) mutation. By the methods of ligand-based quantitative structure-activity relationship and molecular dynamics simulation, we further recommend that aknadicine and 16beta-hydroxy-19s-vindolinine N-oxide from the traditional Chinese medicine are potent novel inhibitors for the management of malignant melanoma in the future. Keywords: BRAF inhibitor, structure-based, virtual screening, docking, ligand-based, quantitative structure-activity relationship (QSAR)Tang HCChen YCDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 3131-3146 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Tang HC
Chen YC
Insight into molecular dynamics simulation of BRAF(V600E) and potent novel inhibitors for malignant melanoma
description Hsin-Chieh Tang,1 Yu-Chian Chen1–3 1Department of Biomedical Informatics, Asia University, Taichung, Taiwan; 2Human Genetic Center, Department of Medical Research, 3Research Center for Chinese Medicine and Acupuncture, China Medical University Hospital, Taichung, Taiwan Abstract: BRAF inhibitors have changed the standard therapeutic protocol for advanced or metastatic melanoma which harbored notorious BRAF(V600E) single mutation. However, drug resistance to BRAF inhibitors happens just like other cancer treatment. In this study, we constructed the ideal BRAF(V600E)-modeled structure through homology modeling and introduced the method of structure-based docking or virtual screening from the large compound database. Through certain methods of molecular dynamics simulation, we realized that BRAF(V600E) had quite prominent difference of molecular character or structural variation from the wild-type BRAF protein. It might confer the metamorphic character of advanced melanoma for the patients who harbored BRAF(V600E) mutation. By the methods of ligand-based quantitative structure-activity relationship and molecular dynamics simulation, we further recommend that aknadicine and 16beta-hydroxy-19s-vindolinine N-oxide from the traditional Chinese medicine are potent novel inhibitors for the management of malignant melanoma in the future. Keywords: BRAF inhibitor, structure-based, virtual screening, docking, ligand-based, quantitative structure-activity relationship (QSAR)
format article
author Tang HC
Chen YC
author_facet Tang HC
Chen YC
author_sort Tang HC
title Insight into molecular dynamics simulation of BRAF(V600E) and potent novel inhibitors for malignant melanoma
title_short Insight into molecular dynamics simulation of BRAF(V600E) and potent novel inhibitors for malignant melanoma
title_full Insight into molecular dynamics simulation of BRAF(V600E) and potent novel inhibitors for malignant melanoma
title_fullStr Insight into molecular dynamics simulation of BRAF(V600E) and potent novel inhibitors for malignant melanoma
title_full_unstemmed Insight into molecular dynamics simulation of BRAF(V600E) and potent novel inhibitors for malignant melanoma
title_sort insight into molecular dynamics simulation of braf(v600e) and potent novel inhibitors for malignant melanoma
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/f5f7ebac0d9e4819a3f4cad2e2d2c151
work_keys_str_mv AT tanghc insightintomoleculardynamicssimulationofnbspbrafv600eandpotentnovelinhibitorsfornbspmalignantmelanoma
AT chenyc insightintomoleculardynamicssimulationofnbspbrafv600eandpotentnovelinhibitorsfornbspmalignantmelanoma
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