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Computational modeling and validation studies of 3-D structure of neuraminidase protein of H1N1 influenza A virus and subsequent in silico elucidation of piceid analogues as its potent inhibitors.

Gupta CL, Akhtar S, Bajpaib P, Kandpal KN, Desai GS, Tiwari AK - EXCLI J (2013)

Bottom Line: Further, the developed 3-D model had been employed for docking studies with the class of compounds as Piceid and its analogs.In this context, two novel compounds (ChemBank ID 2110359 and 3075417) were found to be more potent inhibitors of neuraminidase than control drugs as zanamivir and oseltamivir in terms of their robust binding energies, strong inhibition constant (Ki) and better hydrogen bond interactions between the protein-ligand complex.The interaction of these compounds with NA protein has been significantly studied at the molecular level.

View Article: PubMed Central - PubMed

Affiliation: Bioinformatics Centre, Indian Veterinary Research Institute, Izatnagar-243122, India.

ABSTRACT
Emergence of the drug resistant variants of the Influenza A virus in the recent years has aroused a great need for the development of novel neuraminidase inhibitors for controlling the pandemic. The neuraminidase (NA) protein of the influenza virus has been the most potential target for the anti-influenza. However, in the absence of any experimental structure of the drug targeting NA protein of H1N1 influenza A virus as zanamivir and oseltamivir, the comprehensive study of the interaction of the drug molecules with the target protein has been missing. Hence in this study a computational 3-D structure of neuraminidase of H1N1 influenza A virus has been developed using homology modeling technique, and the same was validated for its reliability by ProSA web server in term of energy profile & Z scores and PROCHECK program followed by Ramachandran plot. Further, the developed 3-D model had been employed for docking studies with the class of compounds as Piceid and its analogs. In this context, two novel compounds (ChemBank ID 2110359 and 3075417) were found to be more potent inhibitors of neuraminidase than control drugs as zanamivir and oseltamivir in terms of their robust binding energies, strong inhibition constant (Ki) and better hydrogen bond interactions between the protein-ligand complex. The interaction of these compounds with NA protein has been significantly studied at the molecular level.

No MeSH data available.


Related in: MedlinePlus

Alignment of NA with template 3CYE. Star (*) indicated identical amino acids, colon (:) for similar amino acids and dot (.) for nearly similar ones
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Figure 1: Alignment of NA with template 3CYE. Star (*) indicated identical amino acids, colon (:) for similar amino acids and dot (.) for nearly similar ones

Mentions: The neuraminidase (NA) protein is found localized on the viral surface and subsequently arrests the release of new virions from the infected cell to neighbouring cells. This protein is 378 amino acids long with estimated molecular weight of 41.7 kDa. The similarity searching results in our study reveals that it has 88 % identity and 93 % similarity with the crystal structure of 1918 H1N1 neuraminidase (3CYE), which can be significantly used an excellent template for modeling of NA protein. Owing to this, both the amino acid sequences of target (NA) and template (1918 H1N1 neuraminidase) were aligned (Figure 1(Fig. 1)) with the formation of an alignment file. Modeler program was successfully able to generate a 3D model of NA protein by the satisfaction of spatial restraints using the crystal structure 3CYE. A total of five models was generated by modeler and one of which was selected as a model of target NA protein.


Computational modeling and validation studies of 3-D structure of neuraminidase protein of H1N1 influenza A virus and subsequent in silico elucidation of piceid analogues as its potent inhibitors.

Gupta CL, Akhtar S, Bajpaib P, Kandpal KN, Desai GS, Tiwari AK - EXCLI J (2013)

Alignment of NA with template 3CYE. Star (*) indicated identical amino acids, colon (:) for similar amino acids and dot (.) for nearly similar ones
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556016&req=5

Figure 1: Alignment of NA with template 3CYE. Star (*) indicated identical amino acids, colon (:) for similar amino acids and dot (.) for nearly similar ones
Mentions: The neuraminidase (NA) protein is found localized on the viral surface and subsequently arrests the release of new virions from the infected cell to neighbouring cells. This protein is 378 amino acids long with estimated molecular weight of 41.7 kDa. The similarity searching results in our study reveals that it has 88 % identity and 93 % similarity with the crystal structure of 1918 H1N1 neuraminidase (3CYE), which can be significantly used an excellent template for modeling of NA protein. Owing to this, both the amino acid sequences of target (NA) and template (1918 H1N1 neuraminidase) were aligned (Figure 1(Fig. 1)) with the formation of an alignment file. Modeler program was successfully able to generate a 3D model of NA protein by the satisfaction of spatial restraints using the crystal structure 3CYE. A total of five models was generated by modeler and one of which was selected as a model of target NA protein.

Bottom Line: Further, the developed 3-D model had been employed for docking studies with the class of compounds as Piceid and its analogs.In this context, two novel compounds (ChemBank ID 2110359 and 3075417) were found to be more potent inhibitors of neuraminidase than control drugs as zanamivir and oseltamivir in terms of their robust binding energies, strong inhibition constant (Ki) and better hydrogen bond interactions between the protein-ligand complex.The interaction of these compounds with NA protein has been significantly studied at the molecular level.

View Article: PubMed Central - PubMed

Affiliation: Bioinformatics Centre, Indian Veterinary Research Institute, Izatnagar-243122, India.

ABSTRACT
Emergence of the drug resistant variants of the Influenza A virus in the recent years has aroused a great need for the development of novel neuraminidase inhibitors for controlling the pandemic. The neuraminidase (NA) protein of the influenza virus has been the most potential target for the anti-influenza. However, in the absence of any experimental structure of the drug targeting NA protein of H1N1 influenza A virus as zanamivir and oseltamivir, the comprehensive study of the interaction of the drug molecules with the target protein has been missing. Hence in this study a computational 3-D structure of neuraminidase of H1N1 influenza A virus has been developed using homology modeling technique, and the same was validated for its reliability by ProSA web server in term of energy profile & Z scores and PROCHECK program followed by Ramachandran plot. Further, the developed 3-D model had been employed for docking studies with the class of compounds as Piceid and its analogs. In this context, two novel compounds (ChemBank ID 2110359 and 3075417) were found to be more potent inhibitors of neuraminidase than control drugs as zanamivir and oseltamivir in terms of their robust binding energies, strong inhibition constant (Ki) and better hydrogen bond interactions between the protein-ligand complex. The interaction of these compounds with NA protein has been significantly studied at the molecular level.

No MeSH data available.


Related in: MedlinePlus