tetano
Editor, Senior Moderator
Mol Inform. 2014 Mar;33(3):240-9. doi: 10.1002/minf.201300117. Epub 2014 Mar 11.
[h=1]Insights from QM/MM Modeling the 3D Structure of the 2009 H1N1 Influenza A Virus Neuraminidase and Its Binding Interactions with Antiviral Drugs.[/h] Wang YT[SUP]1[/SUP], Chen YC[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Control of drug release through the inhibition of neuraminidase-1 has been identified as a potential target for the treatment of H1N1 influenza; however, the drug binding mode of neuraminidase is not yet completely understood. In this work, we propose a model for a neuraminidase-1 complex based on four known X-ray structures of drug/neuraminidase-1 complexes. Specifically, H1N1 neuraminidase-1 complexed with 4 drugs (zanamivir, laninamivir, laninamivir octanoate and oseltamivir) was first investigated using a combined quantum mechanical and molecular mechanical (QM/MM) approach. Based on these structures, a model for the H1N1 neuraminidase-1 complex was proposed and simulated using the same computational protocol. Implications to drug/H1N1 neuraminidase-1 binding modes are discussed. From our simulations, the predicted binding free energies of the four drugs are in good agreement with the experimental results, with the correlation coefficient being 0.84.
? 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
[h=4]KEYWORDS:[/h] H1N1; MMPBSA; Molecular dynamics; Neuramindase; QMMM
PMID: 27485692 DOI: 10.1002/minf.201300117
[PubMed]
[h=1]Insights from QM/MM Modeling the 3D Structure of the 2009 H1N1 Influenza A Virus Neuraminidase and Its Binding Interactions with Antiviral Drugs.[/h] Wang YT[SUP]1[/SUP], Chen YC[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Control of drug release through the inhibition of neuraminidase-1 has been identified as a potential target for the treatment of H1N1 influenza; however, the drug binding mode of neuraminidase is not yet completely understood. In this work, we propose a model for a neuraminidase-1 complex based on four known X-ray structures of drug/neuraminidase-1 complexes. Specifically, H1N1 neuraminidase-1 complexed with 4 drugs (zanamivir, laninamivir, laninamivir octanoate and oseltamivir) was first investigated using a combined quantum mechanical and molecular mechanical (QM/MM) approach. Based on these structures, a model for the H1N1 neuraminidase-1 complex was proposed and simulated using the same computational protocol. Implications to drug/H1N1 neuraminidase-1 binding modes are discussed. From our simulations, the predicted binding free energies of the four drugs are in good agreement with the experimental results, with the correlation coefficient being 0.84.
? 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
[h=4]KEYWORDS:[/h] H1N1; MMPBSA; Molecular dynamics; Neuramindase; QMMM
PMID: 27485692 DOI: 10.1002/minf.201300117
[PubMed]