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
Identifieur interne : 000029 ( Pmc/Curation ); précédent : 000028; suivant : 000030Computational 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
Auteurs : Chhedi Lal Gupta [Inde] ; Salman Akhtar [Inde] ; Preeti Bajpaib [Inde] ; K. N. Kandpal [Inde] ; G. S. Desai [Inde] ; Ashok K. Tiwari [Inde]Source :
- EXCLI Journal [ 1611-2156 ] ; 2013.
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.
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PubMed: 26417228
PubMed Central: 4556016
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">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</title><author><name sortKey="Gupta, Chhedi Lal" sort="Gupta, Chhedi Lal" uniqKey="Gupta C" first="Chhedi Lal" last="Gupta">Chhedi Lal Gupta</name><affiliation wicri:level="1"><nlm:aff id="A1">Bioinformatics Centre, Indian Veterinary Research Institute, Izatnagar–243122, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Bioinformatics Centre, Indian Veterinary Research Institute, Izatnagar–243122</wicri:regionArea></affiliation></author><author><name sortKey="Akhtar, Salman" sort="Akhtar, Salman" uniqKey="Akhtar S" first="Salman" last="Akhtar">Salman Akhtar</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Biotechnology, Microbiology and Bioinformatics, Integral University, Lucknow-226026, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Biotechnology, Microbiology and Bioinformatics, Integral University, Lucknow-226026</wicri:regionArea></affiliation></author><author><name sortKey="Bajpaib, Preeti" sort="Bajpaib, Preeti" uniqKey="Bajpaib P" first="Preeti" last="Bajpaib">Preeti Bajpaib</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Biotechnology, Microbiology and Bioinformatics, Integral University, Lucknow-226026, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Biotechnology, Microbiology and Bioinformatics, Integral University, Lucknow-226026</wicri:regionArea></affiliation></author><author><name sortKey="Kandpal, K N" sort="Kandpal, K N" uniqKey="Kandpal K" first="K. N." last="Kandpal">K. N. Kandpal</name><affiliation wicri:level="1"><nlm:aff id="A1">Bioinformatics Centre, Indian Veterinary Research Institute, Izatnagar–243122, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Bioinformatics Centre, Indian Veterinary Research Institute, Izatnagar–243122</wicri:regionArea></affiliation></author><author><name sortKey="Desai, G S" sort="Desai, G S" uniqKey="Desai G" first="G. S." last="Desai">G. S. Desai</name><affiliation wicri:level="1"><nlm:aff id="A3">Division of Animal Biotechnology, Indian Veterinary Research Institute, Izatnagar-243122, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Division of Animal Biotechnology, Indian Veterinary Research Institute, Izatnagar-243122</wicri:regionArea></affiliation></author><author><name sortKey="Tiwari, Ashok K" sort="Tiwari, Ashok K" uniqKey="Tiwari A" first="Ashok K." last="Tiwari">Ashok K. 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N." last="Kandpal">K. N. Kandpal</name><affiliation wicri:level="1"><nlm:aff id="A1">Bioinformatics Centre, Indian Veterinary Research Institute, Izatnagar–243122, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Bioinformatics Centre, Indian Veterinary Research Institute, Izatnagar–243122</wicri:regionArea></affiliation></author><author><name sortKey="Desai, G S" sort="Desai, G S" uniqKey="Desai G" first="G. S." last="Desai">G. S. Desai</name><affiliation wicri:level="1"><nlm:aff id="A3">Division of Animal Biotechnology, Indian Veterinary Research Institute, Izatnagar-243122, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Division of Animal Biotechnology, Indian Veterinary Research Institute, Izatnagar-243122</wicri:regionArea></affiliation></author><author><name sortKey="Tiwari, Ashok K" sort="Tiwari, Ashok K" uniqKey="Tiwari A" first="Ashok K." last="Tiwari">Ashok K. Tiwari</name><affiliation wicri:level="1"><nlm:aff id="A1">Bioinformatics Centre, Indian Veterinary Research Institute, Izatnagar–243122, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Bioinformatics Centre, Indian Veterinary Research Institute, Izatnagar–243122</wicri:regionArea></affiliation></author></analytic><series><title level="j">EXCLI Journal</title><idno type="eISSN">1611-2156</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">EXCLI J</journal-id><journal-id journal-id-type="iso-abbrev">EXCLI J</journal-id><journal-id journal-id-type="publisher-id">EXCLI J</journal-id><journal-title-group><journal-title>EXCLI Journal</journal-title></journal-title-group><issn pub-type="epub">1611-2156</issn><publisher><publisher-name>Leibniz Research Centre for Working Environment and Human Factors</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26417228</article-id><article-id pub-id-type="pmc">4556016</article-id><article-id pub-id-type="publisher-id">2013-150</article-id><article-id pub-id-type="publisher-id">Doc215</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject></subj-group></article-categories><title-group><article-title>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</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Gupta</surname><given-names>Chhedi Lal</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Akhtar</surname><given-names>Salman</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Bajpaib</surname><given-names>Preeti</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Kandpal</surname><given-names>K. N.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Desai</surname><given-names>G. S.</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Tiwari</surname><given-names>Ashok K.</given-names></name><xref ref-type="corresp" rid="COR1">*</xref><xref ref-type="aff" rid="A1">1</xref></contrib></contrib-group><aff id="A1"><label>1</label>Bioinformatics Centre, Indian Veterinary Research Institute, Izatnagar–243122, India</aff><aff id="A2"><label>2</label>Department of Biotechnology, Microbiology and Bioinformatics, Integral University, Lucknow-226026, India</aff><aff id="A3"><label>3</label>Division of Animal Biotechnology, Indian Veterinary Research Institute, Izatnagar-243122, India</aff><author-notes><corresp id="COR1">*To whom correspondence should be addressed: Ashok K. Tiwari, Bioinformatics Centre, Indian Veterinary Research Institute, Izatnagar–243122, India, Mobile: +91– 9457257425, E-mail: <email>ashokktiwari63@gmail.com, aktiwari63@yahoo.com</email></corresp></author-notes><pub-date pub-type="epub"><day>12</day><month>3</month><year>2013</year></pub-date><pub-date pub-type="collection"><year>2013</year></pub-date><volume>12</volume><fpage>215</fpage><lpage>225</lpage><history><date date-type="received"><day>06</day><month>2</month><year>2013</year></date><date date-type="accepted"><day>25</day><month>2</month><year>2013</year></date></history><permissions><copyright-statement>Copyright © 2013 Gupta et al.</copyright-statement><copyright-year>2013</copyright-year><license license-type="open-access" xlink:href="http://www.excli.de/documents/assignment_of_rights.pdf"><license-p>This is an Open Access article distributed under the following Assignment of Rights http://www.excli.de/documents/assignment_of_rights.pdf. You are free to copy, distribute and transmit the work, provided the original author and source are credited.</license-p></license></permissions><self-uri xlink:type="simple" xlink:href="http://www.excli.de/vol12/Tiwari/Tiwari_12032013_proof.pdf">This article is available from http://www.excli.de/vol12/Tiwari/Tiwari_12032013_proof.pdf</self-uri><abstract><p>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.</p></abstract><kwd-group><kwd>neuraminidase, modeler</kwd><kwd>Ramachandran plot</kwd><kwd>molecular docking</kwd><kwd>anti-influenza drugs</kwd><kwd>piceid</kwd></kwd-group></article-meta></front><floats-group><fig id="T1" position="float"><label>Table 1</label><caption><title>Ramachandran plot calculation of 3-D model of NA protein and template protein (3CYE)</title></caption><graphic xlink:href="EXCLI-12-215-t-001"></graphic></fig><fig id="T2" position="float"><label>Table 2</label><caption><title>Molecular docking studies of piceid and their analogs with NA protein</title></caption><graphic xlink:href="EXCLI-12-215-t-002"></graphic></fig><fig id="T3" position="float"><label>Table 3</label><caption><title>Interaction energies of compound 2110359, 3075417, zanamivir and oseltamivir with NA (Kcal/mol) obtained from molecular docking</title></caption><graphic xlink:href="EXCLI-12-215-t-003"></graphic></fig><fig id="T4" position="float"><label>Table 4</label><caption><title>Hydrogen bond interaction studies of compound 2110359, 3075417, zanamivir and oseltamivir with NA</title></caption><graphic xlink:href="EXCLI-12-215-t-004"></graphic></fig><fig id="F1" position="float"><label>Figure 1</label><caption><title>Alignment of NA with template 3CYE. Star (*) indicated identical amino acids, colon (:) for similar amino acids and dot (.) for nearly similar ones</title></caption><graphic xlink:href="EXCLI-12-215-g-001"></graphic></fig><fig id="F2" position="float"><label>Figure 2</label><caption><title>Ramachandran plot of NA model showing 89.8 % of amino acid residues in core region (red color)</title></caption><graphic xlink:href="EXCLI-12-215-g-002"></graphic></fig><fig id="F3" position="float"><label>Figure 3</label><caption><title>Superposition of NA model with its template protein 1918 H1N1 influenza virus neuraminidase. Magenta ribbon representation of NA model and Cyan ribbon representation of 1918 H1N1 influenza virus neuraminidase. Their root mean square deviation (RMSD) value was 0.151 Å.</title></caption><graphic xlink:href="EXCLI-12-215-g-003"></graphic></fig><fig id="F4" position="float"><label>Figure 4</label><caption><title>The Z score plot represents Z score value of proteins. The two dark black points represent Z score of the NA model and template protein (3CYE).</title></caption><graphic xlink:href="EXCLI-12-215-g-004"></graphic></fig><fig id="F5" position="float"><label>Figure 5</label><caption><title>Energy profiles of NA model and template protein (3CYE) predicted by ProSA web server</title></caption><graphic xlink:href="EXCLI-12-215-g-005"></graphic></fig><fig id="F6" position="float"><label>Figure 6</label><caption><title>The 2D chemical structure of two novel compounds showing good binding energies (a) 2110359, (b) 3075417 and the anti-influenza drugs (c) zanamivir, (d) oseltamivir.</title></caption><graphic xlink:href="EXCLI-12-215-g-006"></graphic></fig><fig id="F7" position="float"><label>Figure 7</label><caption><title>a: Surrounding residues and hydrogen bonds formed between compound 2110359 (in green color) and neuraminidase. b: Surrounding residues and hydrogen bonds formed between compound 3075417 (in green color) and neuraminidase. c: Surrounding residues and hydrogen bonds formed between zanamivir (in green color) and neuraminidase. d: Surrounding residues and hydrogen bonds formed between oseltamivir (in green color) and neuraminidase. Hydrogen bonds are shown by green dash line.</title></caption><graphic xlink:href="EXCLI-12-215-g-007"></graphic></fig></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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