DICP OpenIR
Computer-Based De Novo Designs of Tripeptides as Novel Neuraminidase Inhibitors
Yang, Zhiwei1; Yang, Gang1,2; Zu, Yuangang1; Fu, Yujie1; Zhou, Lijun1
KeywordDocking Influenza Neuraminidase Inhibitors Tripeptides H-bonds De Novo Drug Designs
Source PublicationINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
2010-12-01
DOI10.3390/ijms11124932
Volume11Issue:12Pages:4932-4951
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Physical Sciences
WOS SubjectChemistry, Multidisciplinary
WOS Research AreaChemistry
WOS KeywordINFLUENZA-VIRUS NEURAMINIDASE ; FREE-ENERGY CALCULATIONS ; AMINO-ACID ZWITTERIONS ; A H5N1 INFECTION ; MOLECULAR-DYNAMICS ; AVIAN INFLUENZA ; PEPTIDE DRUGS ; RESISTANCE ; BINDING ; OSELTAMIVIR
AbstractThe 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.
Language英语
WOS IDWOS:000285708000011
Citation statistics
Cited Times:11[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/142111
Collection中国科学院大连化学物理研究所
Affiliation1.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
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.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Yang, Zhiwei]'s Articles
[Yang, Gang]'s Articles
[Zu, Yuangang]'s Articles
Baidu academic
Similar articles in Baidu academic
[Yang, Zhiwei]'s Articles
[Yang, Gang]'s Articles
[Zu, Yuangang]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Yang, Zhiwei]'s Articles
[Yang, Gang]'s Articles
[Zu, Yuangang]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.