Novel natural inhibitors targeting B-RAF(V600E) by computational study
The aim of this research was to screen the ZINC15 database to select lead compounds and drug candidates which can inhibit B-RAF (V600E). In order to identify drugs potentially inhibited B-RAF (V600E), numerous modules of Discovery Studio 4.5 were employed. Structure-based screening using LibDock was...
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Online Access: | http://dx.doi.org/10.1080/21655979.2021.1943113 |
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doaj-484132269ac145e09190f4049c3794ba2021-07-15T13:47:55ZengTaylor & Francis GroupBioengineered2165-59792165-59872021-01-011212970298310.1080/21655979.2021.19431131943113Novel natural inhibitors targeting B-RAF(V600E) by computational studyBo Wu0Zhiyun Zhang1Gaojing Dou2Xiaye Lv3Junliang Ge4Hongyu Wang5Haoqun Xie6Dong Zhu7the First Bethune Hospital of Jilin UniversityJilin University, Street Xinmin 126Jilin University, Street Xinmin 126the First Clinical Medical School of Lanzhou University, No.1, Donggangxi Rd, Chengguan DistrictJilin University, Street Xinmin 126Jilin University, Street Xinmin 126Jilin University, Street Xinmin 126the First Bethune Hospital of Jilin UniversityThe aim of this research was to screen the ZINC15 database to select lead compounds and drug candidates which can inhibit B-RAF (V600E). In order to identify drugs potentially inhibited B-RAF (V600E), numerous modules of Discovery Studio 4.5 were employed. Structure-based screening using LibDock was carried out followed by ADME (absorption, distribution, metabolism, excretion) and toxicity prediction. CDOCKER was performed to demonstrate the binding affinity and mechanism between ligands and B-RAF(V600E). To evaluate whether ligand-receptor complexes were stable, molecular dynamics were employed. Two novel natural compounds (ZINC000100168592 and ZINC000049784088) from ZINC15 database were found binding to B-RAF(V600E) with more favorable interaction energy in comparison with the reference drug Vemurafenib. Also, they were predicted with less ames mutagenicity, rodent carcinogenicity, non-developmental toxic potential and tolerance to cytochrome P450 2D6 (CYP2D6). The molecular dynamics simulation analysis indicated that the compound-B-RAF(V600E) complexes had more favorable potential energy compared with Vemurafenib and they can exist in natural environments stably. The result of this study shows that ZINC000100168592 and ZINC000049784088 are ideal leading potential compounds to inhibit B-RAF(V600E). The findings of this study and these selected drug candidates greatly contributed to the medication design and improvement of B-RAF(V600E) and other proteins.http://dx.doi.org/10.1080/21655979.2021.1943113b-raf(v600e)vemurafenibdrug treatmentdiscovery studiovirtual screening |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bo Wu Zhiyun Zhang Gaojing Dou Xiaye Lv Junliang Ge Hongyu Wang Haoqun Xie Dong Zhu |
spellingShingle |
Bo Wu Zhiyun Zhang Gaojing Dou Xiaye Lv Junliang Ge Hongyu Wang Haoqun Xie Dong Zhu Novel natural inhibitors targeting B-RAF(V600E) by computational study Bioengineered b-raf(v600e) vemurafenib drug treatment discovery studio virtual screening |
author_facet |
Bo Wu Zhiyun Zhang Gaojing Dou Xiaye Lv Junliang Ge Hongyu Wang Haoqun Xie Dong Zhu |
author_sort |
Bo Wu |
title |
Novel natural inhibitors targeting B-RAF(V600E) by computational study |
title_short |
Novel natural inhibitors targeting B-RAF(V600E) by computational study |
title_full |
Novel natural inhibitors targeting B-RAF(V600E) by computational study |
title_fullStr |
Novel natural inhibitors targeting B-RAF(V600E) by computational study |
title_full_unstemmed |
Novel natural inhibitors targeting B-RAF(V600E) by computational study |
title_sort |
novel natural inhibitors targeting b-raf(v600e) by computational study |
publisher |
Taylor & Francis Group |
series |
Bioengineered |
issn |
2165-5979 2165-5987 |
publishDate |
2021-01-01 |
description |
The aim of this research was to screen the ZINC15 database to select lead compounds and drug candidates which can inhibit B-RAF (V600E). In order to identify drugs potentially inhibited B-RAF (V600E), numerous modules of Discovery Studio 4.5 were employed. Structure-based screening using LibDock was carried out followed by ADME (absorption, distribution, metabolism, excretion) and toxicity prediction. CDOCKER was performed to demonstrate the binding affinity and mechanism between ligands and B-RAF(V600E). To evaluate whether ligand-receptor complexes were stable, molecular dynamics were employed. Two novel natural compounds (ZINC000100168592 and ZINC000049784088) from ZINC15 database were found binding to B-RAF(V600E) with more favorable interaction energy in comparison with the reference drug Vemurafenib. Also, they were predicted with less ames mutagenicity, rodent carcinogenicity, non-developmental toxic potential and tolerance to cytochrome P450 2D6 (CYP2D6). The molecular dynamics simulation analysis indicated that the compound-B-RAF(V600E) complexes had more favorable potential energy compared with Vemurafenib and they can exist in natural environments stably. The result of this study shows that ZINC000100168592 and ZINC000049784088 are ideal leading potential compounds to inhibit B-RAF(V600E). The findings of this study and these selected drug candidates greatly contributed to the medication design and improvement of B-RAF(V600E) and other proteins. |
topic |
b-raf(v600e) vemurafenib drug treatment discovery studio virtual screening |
url |
http://dx.doi.org/10.1080/21655979.2021.1943113 |
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