Molecular Dynamic Simulation to Explore the Molecular Basis of Btk-PH Domain Interaction with Ins(1,3,4,5)P4
文献类型：期刊论文
| 作者 | Lu, Dan2; Jiang, Junfeng2; Liang, Zhongjie2,3; Sun, Maomin2; Luo, Cheng2,3 ; Shen, Bairong1,2; Hu, Guang2
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| 刊名 | SCIENTIFIC WORLD JOURNAL
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| 出版日期 | 2013 |
| ISSN号 | 1537-744X |
| DOI | 10.1155/2013/580456 |
| 文献子类 | Article |
| 英文摘要 | Bruton's tyrosine kinase contains a pleckstrin homology domain, and it specifically binds inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5) P4), which is involved in the maturation of B cells. In this paper, we studied 12 systems including the wild type and 11 mutants, K12R, S14F, K19E, R28C/H, E41K, L11P, F25S, Y40N, and K12R-R28C/H, to investigate any change in the ligand binding site of each mutant. Molecular dynamics simulations combined with the method of molecular mechanics/Poisson-Boltzmann solvent-accessible surface area have been applied to the twelve systems, and reasonable mutant structures and their binding free energies have been obtained as criteria in the final classification. As a result, five structures, K12R, K19E, R28C/H, and E41K mutants, were classified as "functional mutations," whereas L11P, S14F, F25S, and Y40N were grouped into "folding mutations. "This rigorous study of the binding affinity of each of the mutants and their classification provides some new insights into the biological function of the Btk-PH domain and related mutation-causing diseases. |
| WOS关键词 | PLECKSTRIN-HOMOLOGY DOMAIN ; BRUTONS TYROSINE KINASE ; X-LINKED AGAMMAGLOBULINEMIA ; XLA-CAUSING MUTATIONS ; MECHANICAL CALCULATIONS ; SIGNALING PROTEINS ; FREE-ENERGIES ; FORCE-FIELD ; MM-PBSA ; BINDING |
| 资助项目 | National Natural Science Foundation of China[21203131] ; National Natural Science Foundation of China[31170795] ; National Natural Science Foundation of China[20872107] ; National Natural Science Foundation of China[20972174] ; National Natural Science Foundation of China[91029704] ; 863 Program[SS2012AA021103] ; Chinese Academy of Sciences[XDA01040305] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000327161200001 |
| 出版者 | HINDAWI PUBLISHING CORPORATION |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277778]  |
| 专题 | 药物发现与设计中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Hu, Guang |
| 作者单位 | 1.Soochow Univ, Coll Med, Dept Bioinformat, Suzhou 215123, Peoples R China 2.Soochow Univ, Ctr Syst Biol, Suzhou 215006, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Lu, Dan,Jiang, Junfeng,Liang, Zhongjie,et al. Molecular Dynamic Simulation to Explore the Molecular Basis of Btk-PH Domain Interaction with Ins(1,3,4,5)P4[J]. SCIENTIFIC WORLD JOURNAL,2013. |
| APA | Lu, Dan.,Jiang, Junfeng.,Liang, Zhongjie.,Sun, Maomin.,Luo, Cheng.,...&Hu, Guang.(2013).Molecular Dynamic Simulation to Explore the Molecular Basis of Btk-PH Domain Interaction with Ins(1,3,4,5)P4.SCIENTIFIC WORLD JOURNAL. |
| MLA | Lu, Dan,et al."Molecular Dynamic Simulation to Explore the Molecular Basis of Btk-PH Domain Interaction with Ins(1,3,4,5)P4".SCIENTIFIC WORLD JOURNAL (2013). |
入库方式： OAI收割
来源：上海药物研究所
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