tetano
Editor, Senior Moderator
Curr Comput Aided Drug Des. 2016 Jul 13. [Epub ahead of print]
[h=1]A Computational Model for Docking of Noncompetitive Neuraminidase Inhibitors and Probing their Binding Interactions with Neuraminidase of Influenza Virus H5N1.[/h] Chintakrindi AS, Martis EA, Gohil DJ, Kothari ST, Chowdhary AS, Coutinho EC, Kanyalkar MA[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] A computational model was developed using molecular docking methodology coupled with molecular dynamics simulation to study the binding pattern of noncompetitive inhibitors of neuraminidase (NA). Few naturally occurring NA noncompetitive inhibitors were docked in the regulatory site of H5N1-NA and the binding interactions of endogenous ligand sialic acid in the active site was probed using molecular dynamics (MD) studies. Docking and MD simulation studies demonstrated that the sialic acid was docked in non-native pose owing to change in active site. The alteration in active site was due to change in orientation of Arg 371, one of the critical residues involved in binding of sialic acid. Based on the above-developed model newer analogs of the natural inhibitors were designed. Furthermore, a representative chalcone and flavone derivative was synthesized and evaluated for NA noncompetitive inhibition. The activity of synthesized chalcone derivative was similar to natural analog (isoliquiritgenin). Lineweaver-Burk plots for these synthesized representative derivatives confirmed their noncompetitive inhibition as illustrated by computational studies.
PMID: 27412704
[PubMed - as supplied by publisher]
[h=1]A Computational Model for Docking of Noncompetitive Neuraminidase Inhibitors and Probing their Binding Interactions with Neuraminidase of Influenza Virus H5N1.[/h] Chintakrindi AS, Martis EA, Gohil DJ, Kothari ST, Chowdhary AS, Coutinho EC, Kanyalkar MA[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] A computational model was developed using molecular docking methodology coupled with molecular dynamics simulation to study the binding pattern of noncompetitive inhibitors of neuraminidase (NA). Few naturally occurring NA noncompetitive inhibitors were docked in the regulatory site of H5N1-NA and the binding interactions of endogenous ligand sialic acid in the active site was probed using molecular dynamics (MD) studies. Docking and MD simulation studies demonstrated that the sialic acid was docked in non-native pose owing to change in active site. The alteration in active site was due to change in orientation of Arg 371, one of the critical residues involved in binding of sialic acid. Based on the above-developed model newer analogs of the natural inhibitors were designed. Furthermore, a representative chalcone and flavone derivative was synthesized and evaluated for NA noncompetitive inhibition. The activity of synthesized chalcone derivative was similar to natural analog (isoliquiritgenin). Lineweaver-Burk plots for these synthesized representative derivatives confirmed their noncompetitive inhibition as illustrated by computational studies.
PMID: 27412704
[PubMed - as supplied by publisher]