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J Biomol Struct Dyn. 2019 Oct 9:1-12. doi: 10.1080/07391102.2019.1677500. [Epub ahead of print] [h=1]Design of fluorinated sialic acid analog inhibitor to H5 Hemagglutinin of H5N1 Influenza virus through Molecular Dynamics simulation study.[/h]
Jeyaram RA[SUP]1[/SUP], Anu Radha C[SUP]1[/SUP], Gromiha MM[SUP]2[/SUP], Veluraja K[SUP]1[/SUP].
[h=3]Author information[/h] 1 Research Laboratory of Molecular Biophysics, Department of Physics, School of Advanced Sciences, Vellore Institute of Technology , Vellore , Tamil Nadu , India. 2 Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras , Chennai , Tamil Nadu , India.
[h=3]Abstract[/h] Influenza epidemics and pandemics are caused by influenza A virus. The cell surface protein of hemagglutinin and neuraminidase are responsible for viral infection and release of progeny virus on the host cell membrane. Now 18 hemagglutinin and 11 neuraminidase subtypes are identified. The avian influenza virus of H5N1 is an emergent threat to public health issues. To control the influenza viral infection it is necessary to develop antiviral inhibitors and vaccination. In the present investigation we carried out 50 ns Molecular Dynamics simulation on H5 hemagglutinin of Influenza A virus H5N1 complexed with fluorinated sialic acid by substituting fluorine atoms at any two hydroxyls of sialic acid by considering combinatorial combination. The binding affinity between the protein - ligand complex system is investigated by calculating pair interaction energy and MM-PBSA binding free energy. All the complex structures are stabilized by hydrogen bonding interactions between the H5 protein and the ligand fluorinated sialic acid. It is concluded from all the analyses that the fluorinated complexes enhance the inhibiting potency against H5 hemagglutinin and the order of inhibiting potency is SIA-F9 ≫ SIA-F2 ≈ SIA-F7 ≈ SIA-F2F4 ≈ SIA-F2F9 ≈ SIA-F7F9 > SIA-F7F8 ≈ SIA-F2F8 ≈ SIA-F8F9 > SIA-F4 ≈ SIA-F4F7 ≈ SIA-F4F8 ≈ SIA-F8 ≈ SIA-F2F7 ≈ SIA > SIA-F4F9. This study suggests that one can design the inhibitor by using the mono fluorinated models SIA-F9, SIA-F2 and SIA-F7 and difluorinated models SIA-F2F4, SIA-F2F9 and SIA-F7F9 to inhibit H5 of H5N1 to avoid Influenza A viral infection. Abbreviations: HA Hemagglutinin MD Molecular Dynamics MM-PBSA Molecular Mechanics - Poisson Boltzmann Surface Area NA Neuraminidase NAMD NAnoscale Molecular Dynamics PMEMD Particle Mesh Ewald Molecular Dynamics SIA Sialic acid VMD Visual Molecular Dynamics.
[h=4]KEYWORDS:[/h] H5N1; MM-PBSA; Molecular Dynamics; NAMD; Sialic acid
PMID: 31594458 DOI: 10.1080/07391102.2019.1677500
Jeyaram RA[SUP]1[/SUP], Anu Radha C[SUP]1[/SUP], Gromiha MM[SUP]2[/SUP], Veluraja K[SUP]1[/SUP].
[h=3]Author information[/h] 1 Research Laboratory of Molecular Biophysics, Department of Physics, School of Advanced Sciences, Vellore Institute of Technology , Vellore , Tamil Nadu , India. 2 Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras , Chennai , Tamil Nadu , India.
[h=3]Abstract[/h] Influenza epidemics and pandemics are caused by influenza A virus. The cell surface protein of hemagglutinin and neuraminidase are responsible for viral infection and release of progeny virus on the host cell membrane. Now 18 hemagglutinin and 11 neuraminidase subtypes are identified. The avian influenza virus of H5N1 is an emergent threat to public health issues. To control the influenza viral infection it is necessary to develop antiviral inhibitors and vaccination. In the present investigation we carried out 50 ns Molecular Dynamics simulation on H5 hemagglutinin of Influenza A virus H5N1 complexed with fluorinated sialic acid by substituting fluorine atoms at any two hydroxyls of sialic acid by considering combinatorial combination. The binding affinity between the protein - ligand complex system is investigated by calculating pair interaction energy and MM-PBSA binding free energy. All the complex structures are stabilized by hydrogen bonding interactions between the H5 protein and the ligand fluorinated sialic acid. It is concluded from all the analyses that the fluorinated complexes enhance the inhibiting potency against H5 hemagglutinin and the order of inhibiting potency is SIA-F9 ≫ SIA-F2 ≈ SIA-F7 ≈ SIA-F2F4 ≈ SIA-F2F9 ≈ SIA-F7F9 > SIA-F7F8 ≈ SIA-F2F8 ≈ SIA-F8F9 > SIA-F4 ≈ SIA-F4F7 ≈ SIA-F4F8 ≈ SIA-F8 ≈ SIA-F2F7 ≈ SIA > SIA-F4F9. This study suggests that one can design the inhibitor by using the mono fluorinated models SIA-F9, SIA-F2 and SIA-F7 and difluorinated models SIA-F2F4, SIA-F2F9 and SIA-F7F9 to inhibit H5 of H5N1 to avoid Influenza A viral infection. Abbreviations: HA Hemagglutinin MD Molecular Dynamics MM-PBSA Molecular Mechanics - Poisson Boltzmann Surface Area NA Neuraminidase NAMD NAnoscale Molecular Dynamics PMEMD Particle Mesh Ewald Molecular Dynamics SIA Sialic acid VMD Visual Molecular Dynamics.
[h=4]KEYWORDS:[/h] H5N1; MM-PBSA; Molecular Dynamics; NAMD; Sialic acid
PMID: 31594458 DOI: 10.1080/07391102.2019.1677500