Molecular Dynamics Simulation of the Selectivity of Fedratinib Complex with JAK2/JAK3

被引：1

作者：

Liu Haichun ^{[1
]}

Lu Shuai ^{[1
]}

Zhang Yanmin ^{[1
]}

Zhou Weineng ^{[1
]}

Yin Lingfeng ^{[1
]}

Zhu Lu ^{[1
]}

Zhao Junnan ^{[1
]}

Lu Tao ^{[1
,2
]}

Chen Yadong ^{[1
]}

机构：

[1] China Pharmaceut Univ, Sch Basic Sci, Nanjing 211198, Jiangsu, Peoples R China

[2] China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China

来源：

CHEMICAL JOURNAL OF CHINESE UNIVERSITIES-CHINESE | 2018年 / 39卷 / 07期

基金：

中国国家自然科学基金;

关键词：

JAK2; inhibitor; Selectivity; Molecular dynamic; Binding free energy; ACCURATE DOCKING; JAK2; DISCOVERY; MUTATION; GLIDE;

D O I：

10.7503/cjcu20170657

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Molecular dynamic (MD) simulation was carried out in both JAK2-Fedratinib and JAK3-Fedratinib complex, respectively. Binding free energy was calculated in utilize the trajectory of MD. The results indicated the energy of JAK2-Fedratinib was lower than that of JAK3-Fedratinib, which demonstrate the different enzyme activity in two kinase. When binding free energy was decomposed into each residue of binding site, it could be found that when molecule occupies the pockets below P-loop and form H-bonds with residues nearby the selectivity for JAK2 over JAK3 may be highlighted. The results can provide insights for further development of more potent and selective JAK2 inhibitors.

引用

页码：1540 / 1548

页数：9

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