QSAR analyses on avian influenza virus neuraminidase inhibitors using CoMFA, CoMSIA, and HQSAR
文献类型：期刊论文
| 作者 | Zheng, Mingyue ; Yu, Kunqian; Liu, Hong; Luo, Xiaomin; Chen, Kaixian; Zhu, Weiliang; Jiang, Hualiang
|
| 刊名 | JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
 |
| 出版日期 | 2006-09 |
| 卷号 | 20期号:9页码:549-566 |
| 关键词 | avian influenza neuraminidase inhibitor docking 3D-QSAR CoMFA CoMSIA HQSAR |
| ISSN号 | 0920-654X |
| DOI | 10.1007/s10822-006-9080-0 |
| 文献子类 | Article |
| 英文摘要 | The recent wide spreading of the H5N1 avian influenza virus (AIV) in Asia, Europe and Africa and its ability to cause fatal infections in human has raised serious concerns about a pending global flu pandemic. Neuraminidase (NA) inhibitors are currently the only option for treatment or prophylaxis in humans infected with this strain. However, drugs currently on the market often meet with rapidly emerging resistant mutants and only have limited application as inadequate supply of synthetic material. To dig out helpful information for designing potent inhibitors with novel structures against the NA, we used automated docking, CoMFA, CoMSIA, and HQSAR methods to investigate the quantitative structure-activity relationship for 126 NA inhibitors (NIs) with great structural diversities and wide range of bioactivities against influenza A virus. Based on the binding conformations discovered via molecular docking into the crystal structure of NA, CoMFA and CoMSIA models were successfully built with the cross-validated q(2) of 0.813 and 0.771, respectively. HQSAR was also carried out as a complementary study in that HQSAR technique does not require 3D information of these compounds and could provide a detailed molecular fragment contribution to the inhibitory activity. These models also show clearly how steric, electrostatic, hydrophobicity, and individual fragments affect the potency of NA inhibitors. In addition, CoMFA and CoMSIA field distributions are found to be in well agreement with the structural characteristics of the corresponding binding sites. Therefore, the final 3D-QSAR models and the information of the inhibitor-enzyme interaction should be useful in developing novel potent NA inhibitors. |
| WOS关键词 | ATOMIC PHYSICOCHEMICAL PARAMETERS ; DIRECTED QUANTITATIVE STRUCTURE ; ITERATIVE PARTIAL EQUALIZATION ; ORBITAL ELECTRONEGATIVITY ; 3-DIMENSIONAL STRUCTURE ; FORCE-FIELD ; STRUCTURAL-ANALYSIS ; BIOLOGICAL-ACTIVITY ; NUCLEIC-ACIDS ; ACTIVE-SITE |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics ; Computer Science |
| 语种 | 英语 |
| WOS记录号 | WOS:000242326300002 |
| 出版者 | SPRINGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273511]  |
| 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 | Zhu, Weiliang |
| 作者单位 | Chinese Acad Sci, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zheng, Mingyue,Yu, Kunqian,Liu, Hong,et al. QSAR analyses on avian influenza virus neuraminidase inhibitors using CoMFA, CoMSIA, and HQSAR[J]. JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN,2006,20(9):549-566. |
| APA | Zheng, Mingyue.,Yu, Kunqian.,Liu, Hong.,Luo, Xiaomin.,Chen, Kaixian.,...&Jiang, Hualiang.(2006).QSAR analyses on avian influenza virus neuraminidase inhibitors using CoMFA, CoMSIA, and HQSAR.JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN,20(9),549-566. |
| MLA | Zheng, Mingyue,et al."QSAR analyses on avian influenza virus neuraminidase inhibitors using CoMFA, CoMSIA, and HQSAR".JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN 20.9(2006):549-566. |
入库方式： OAI收割
来源：上海药物研究所
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