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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

Energy profiles of NA model and template protein (3CYE) predicted by ProSA web server
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Figure 5: Energy profiles of NA model and template protein (3CYE) predicted by ProSA web server

Mentions: The quality of the protein folds of NA model was also evaluated in terms of energy function of amino acid residues. In general, folding energy of the protein showed minimum value as this accounts for the stability and nativity of the molecules. The energy profile of NA model in comparison to that of the X-ray structure of template is presented in Figure 5(Fig. 5). The trend of the variation of the protein folding energy in NA model was in good agreement with that of the X-ray structure of template (3CYE).


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)

Energy profiles of NA model and template protein (3CYE) predicted by ProSA web server
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Energy profiles of NA model and template protein (3CYE) predicted by ProSA web server
Mentions: The quality of the protein folds of NA model was also evaluated in terms of energy function of amino acid residues. In general, folding energy of the protein showed minimum value as this accounts for the stability and nativity of the molecules. The energy profile of NA model in comparison to that of the X-ray structure of template is presented in Figure 5(Fig. 5). The trend of the variation of the protein folding energy in NA model was in good agreement with that of the X-ray structure of template (3CYE).

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