文献类型：期刊文献

英文题名：Integrating docking scores and key interaction profiles to improve the accuracy of molecular docking: towards novel B-Raf(V600E) inhibitors

作者：Hu, Chun-Qi[1,2,4];Li, Kang[1,3];Yao, Ting-Ting[1];Hu, Yong-Zhou[1];Ying, Hua-Zhou[1];Dong, Xiao-Wu[1]

机构：[1]Zhejiang Univ, Zhejiang Prov Key Lab Anticanc Drug Res, Coll Pharmaceut Sci, Hangzhou, Zhejiang, Peoples R China;[2]Shaoxing Univ, Coll Chem & Chem Engn, Shaoxing, Peoples R China;[3]Zhejiang Univ Technol, Collaborat Innovat Ctr Yangtze River Delta Reg Gr, Hangzhou, Zhejiang, Peoples R China;[4]Yongning Pharma, Taizhou, Peoples R China

年份：2017

卷号：8

期号：9

起止页码：1835

外文期刊名：MEDCHEMCOMM

收录：SCI-EXPANDED(收录号：WOS:000411437800011)、、WOS

基金：This study was financially supported by the National Natural Science Foundation of China (81673294, 81502914 and 81502926) and the Science and Technology Planning Project of Zhejiang Province (2016C33067).

语种：英文

外文摘要：A set of ninety-eight B-Raf(V600E) inhibitors was used for the development of a molecular docking based QSAR model using linear and non-linear regression models. The integration of docking scores and key interaction profiles significantly improved the accuracy of the QSAR models, providing reasonable statistical parameters (R-train(2) = 0.935, R-test(2) = 0.728 and Q(CV)(2) = 0.905). The established MD-SVR (molecular docking based SMV regression) model as well as model screening of a natural product database was carried out and two natural products (quercetin and myricetin) with good prediction activities were biologically evaluated. Both compounds exhibited promising B-Raf(V600E) inhibitory activities (IC50Quercetin = 7.59 mu M and IC50Myricetin = 1.56 mu M), suggesting a high reliability and good applicability of the established MD-SVR model in the future development of B-Raf(V600E) inhibitors with high efficacy.