Computer-Based De Novo Designs of Tripeptides as Novel Neuraminidase Inhibitors
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 (InsightII 2005).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.
Zhiwei Yang Fei Wu Gang Yang
1 School of Basic Medical Sciences, Jiamusi University, Jiamusi 154007; Key Laboratory of Forest Pla Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin
国际会议
南京
英文
146-166
2012-05-13（万方平台首次上网日期，不代表论文的发表时间）