Molecular dynamics simulation and density functional theory studies on the active pocket for the binding of paclitaxel to tubulin
文献类型：期刊论文
| 作者 | Xu, Sichuan1,2; Chi, Shaoming2; Jin, Yi2; Shi, Qiang1; Ge, Maofa1; Wang, Shu1; Zhang, Xingkang1 |
| 刊名 | JOURNAL OF MOLECULAR MODELING
 |
| 出版日期 | 2012 |
| 卷号 | 18期号:1页码:377-391 |
| 关键词 | Paclitaxel Tubulin Binding Pocket Md Simulation Dft |
| ISSN号 | 1610-2940 |
| DOI | 10.1007/s00894-011-1083-7 |
| 英文摘要 | Paclitaxel (PTX) is used to treat various cancers, but it also causes serious side effects and resistance. To better design similar compounds with less toxicity and more activity against drug-resistant tumors, it is important to clearly understand the PTX-binding pocket formed by the key residues of active sites on beta-tubulin. Using a docking method, molecular dynamics (MD) simulation and density functional theory (DFT), we identified some residues (such as Arg278, Asp26, Asp226, Glu22, Glu27, His229, Arg369, Lys218, Ser277 and Thr276) on beta-tubulin that are the active sites responsible for interaction with PTX. Another two residues, Leu371 and Gly279, also likely serve as active sites. Most of these sites contact with the "southern hemisphere" of PTX; only one key residue interacts with the "northern hemisphere" of PTX. These key residues can be divided into four groups, which serve as active compositions in the formation of an active pocket for PTX binding to beta-tubulin. This active binding pocket enables a very strong interaction (the strength is predicted to be in the range of -327.8 to -365.7 kJ mol(-1)) between beta-tubulin and PTX, with various orientated conformations. This strong interaction means that PTX possesses a high level of activity against cancer cells, a result that is in good agreement with the clinical mechanism of PTX. The described PTX pocket and key active residues will be applied to probe the mechanism of tumor cells resistant to PTX, and to design novel analogs with superior properties. |
| 语种 | 英语 |
| WOS记录号 | WOS:000298756500036 |
| 出版者 | SPRINGER |
| 源URL | [http://ir.iccas.ac.cn/handle/121111/47897]  |
| 专题 | 中国科学院化学研究所 |
| 通讯作者 | Xu, Sichuan |
| 作者单位 | 1.Chinese Acad Sci, State Key Lab Struct Chem Unstable & Stable Speci, Beijing Natl Lab Mol Sci, Inst Chem, Beijing 100190, Peoples R China 2.Yunnan Univ, Key Lab, Educ Minist Med Chem Nat Resource, Coll Chem Sci & Technol, Kunming 650091, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu, Sichuan,Chi, Shaoming,Jin, Yi,et al. Molecular dynamics simulation and density functional theory studies on the active pocket for the binding of paclitaxel to tubulin[J]. JOURNAL OF MOLECULAR MODELING,2012,18(1):377-391. |
| APA | Xu, Sichuan.,Chi, Shaoming.,Jin, Yi.,Shi, Qiang.,Ge, Maofa.,...&Zhang, Xingkang.(2012).Molecular dynamics simulation and density functional theory studies on the active pocket for the binding of paclitaxel to tubulin.JOURNAL OF MOLECULAR MODELING,18(1),377-391. |
| MLA | Xu, Sichuan,et al."Molecular dynamics simulation and density functional theory studies on the active pocket for the binding of paclitaxel to tubulin".JOURNAL OF MOLECULAR MODELING 18.1(2012):377-391. |
入库方式： OAI收割
来源：化学研究所
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