Molecular dynamics-guided receptor-dependent 4D-QSAR studies of HDACs inhibitors

被引：8

作者：

Hu, Zhihao ^{[1
]}

Lin, Qianxia ^{[2
]}

Liu, Haiyun ^{[2
]}

Zhao, Tiansheng ^{[1
]}

Yang, Bowen ^{[1
]}

Tu, Guogang ^{[1
]}

机构：

[1] NanChang Univ, Sch Pharmaceut Sci, Dept Med Chem, Nanchang 330006, Jiangxi, Peoples R China

[2] Jiangxi Univ Tradit Chinese Med, Nanchang 330006, Jiangxi, Peoples R China

来源：

MOLECULAR DIVERSITY | 2022年 / 26卷 / 02期

关键词：

Hdacs; 4D-QSAR; Molecular dynamics simulations; HISTONE-DEACETYLASE; LQTA-QSAR; MODELS; SET;

D O I：

10.1007/s11030-021-10181-y

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Histone deacetylases (HDACs) were highlighted as a novel category of anticancer targets. Several HDACs inhibitors were approved for therapeutic use in cancer treatment. Comparatively, receptor-dependent 4D-QSAR, LQTA-QSAR, is a new approach which generates conformational ensemble profiles of compounds by molecular dynamics simulations at binding site of enzyme. This work describes a receptor-dependent 4D-QSAR studies on hydroxamate-based HDACs inhibitors. The 4D-QSAR model was generated by multiple linear regression method of QSARINS. Leave-N-out cross-validation (LNO) and Y-randomization were performed to analysis of the independent test set and to verify the robustness of the model. Best 4D-QSAR model showed the following statistics: R-2 = 0.8117, Q(LOO)(2) = 0.6881, Q(LNO)(2) = 0.6830, R-Pred(2) = 0.884. The results may be used for further virtual screening and design for novel HDACs inhibitors. [GRAPHICS] .

引用

页码：757 / 768

页数：12

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