Computer-Based De Novo Designs of Tripeptides as Novel Neuraminidase Inhibitors
文献类型：期刊论文
| 作者 | Yang, Zhiwei1; Yang, Gang1,2; Zu, Yuangang1; Fu, Yujie1; Zhou, Lijun1 |
| 刊名 | international journal of molecular sciences
 |
| 出版日期 | 2010-12-01 |
| 卷号 | 11期号:12页码:4932-4951 |
| 关键词 | docking influenza neuraminidase inhibitors tripeptides H-bonds de novo drug designs |
| 英文摘要 | the latest influenza a (h1n1) pandemic attracted worldwide attention and called for the urgent development of novel antiviral drugs. here, seven tripeptides are designed and explored as neuraminidase (na) inhibitors on the structural basis of known inhibitors. their interactions with na are studied and compared with each other, using flexible docking and molecular dynamics simulations. the various composed tripeptides have respective binding specificities and their interaction energies with na decrease in the order of fri > frv > frt > fhv > frs > frg > yrv (letters corresponding to amino acid code). the arg and phe portions of the tripeptides play important roles during the binding process: arg has strong electrostatic interactions with the key residues asp151, glu119, glu227 and glu277, whereas phe fits well in the hydrophobic cave within the na active site. owing to the introduction of hydrophobic property, the interaction energies of frv and fri are larger; in particular, fri demonstrates the best binding quality and shows potential as a lead compound. in addition, the influence of the chemical states of the terminal amino acids are clarified: it is revealed that the charged states of the n-terminus (nh3+) and c-terminus (coo-) are crucial for the tripeptide inhibitory activities and longer peptides may not be appropriate. in addition, the medium inhibiting activity by acetylation of the n-terminus indicates the possible chemical modifications of fri. experimental efforts are expected in order to actualize the tripeptides as potent na inhibitors in the near future. |
| WOS标题词 | science & technology ; physical sciences |
| 类目[WOS] | chemistry, multidisciplinary |
| 研究领域[WOS] | chemistry |
| 关键词[WOS] | influenza-virus neuraminidase ; free-energy calculations ; amino-acid zwitterions ; a h5n1 infection ; molecular-dynamics ; avian influenza ; peptide drugs ; resistance ; binding ; oseltamivir |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000285708000011 |
| 公开日期 | 2015-11-17 |
| 源URL | [http://159.226.238.44/handle/321008/142034]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 作者单位 | 1.NE Forestry Univ, Minist Educ, Key Lab Forest Plant Ecol, Harbin 150040, Peoples R China 2.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yang, Zhiwei,Yang, Gang,Zu, Yuangang,et al. Computer-Based De Novo Designs of Tripeptides as Novel Neuraminidase Inhibitors[J]. international journal of molecular sciences,2010,11(12):4932-4951. |
| APA | Yang, Zhiwei,Yang, Gang,Zu, Yuangang,Fu, Yujie,&Zhou, Lijun.(2010).Computer-Based De Novo Designs of Tripeptides as Novel Neuraminidase Inhibitors.international journal of molecular sciences,11(12),4932-4951. |
| MLA | Yang, Zhiwei,et al."Computer-Based De Novo Designs of Tripeptides as Novel Neuraminidase Inhibitors".international journal of molecular sciences 11.12(2010):4932-4951. |
入库方式： OAI收割
来源：大连化学物理研究所
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