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题名: Computer-Based De Novo Designs of Tripeptides as Novel Neuraminidase Inhibitors
作者: Yang, Zhiwei1;  Yang, Gang1, 2;  Zu, Yuangang1;  Fu, Yujie1;  Zhou, Lijun1
关键词: docking ;  influenza ;  neuraminidase inhibitors ;  tripeptides ;  H-bonds ;  de novo drug designs
刊名: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
发表日期: 2010-12-01
DOI: 10.3390/ijms11124932
卷: 11, 期:12, 页:4932-4951
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Physical Sciences
类目[WOS]: Chemistry, Multidisciplinary
研究领域[WOS]: Chemistry
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.
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
语种: 英语
WOS记录号: WOS:000285708000011
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/142034
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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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

Recommended Citation:
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.
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