tetano
Editor, Senior Moderator
Interdiscip Sci. 2017 Jun 19. doi: 10.1007/s12539-017-0239-2. [Epub ahead of print]
[h=1]Studies of the Interaction of Influenza Virus RNA Polymerase PAN with Endonuclease Inhibitors.[/h] Dong LH[SUP]1[/SUP], Cao XR[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza virus is a major causative agent of respiratory viral infections, and RNA polymerase catalyzes its replication and transcription activities in infected cell nuclei. Since it is highly conserved in all virus strains, RNA polymerase becomes a key target of anti-influenza virus agents. Although experimental studies have revealed the good inhibitory activity of endonuclease inhibitors to RNA polymerase, the mechanism is still unclear. In this study, the docking and molecular dynamics simulations have been performed to explore the interaction of three kinds of endonuclease inhibitors with the subunit (PA[SUB]N[/SUB]) of RNA polymerase. Our calculations indicate that all these endonuclease inhibitors can bind to the binding pocket of PA[SUB]N[/SUB], in which the electronegative oxygen atoms of the inhibitors form a chelated structure with the two Mn[SUP]2+[/SUP] cations of the active center. The most important interaction between these inhibitors and PA[SUB]N[/SUB] is electrostatic interaction. The electron density of the chelate oxygen atoms determines the magnitude of the electrostatic energy, and the chelated structure and orientation of inhibitors depend largely on the distance between the chelate oxygen atoms.
[h=4]KEYWORDS:[/h] Docking; Influenza virus RNA polymerase; Inhibitor; Molecular dynamics simulation
PMID: 28631174 DOI: 10.1007/s12539-017-0239-2
[h=1]Studies of the Interaction of Influenza Virus RNA Polymerase PAN with Endonuclease Inhibitors.[/h] Dong LH[SUP]1[/SUP], Cao XR[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza virus is a major causative agent of respiratory viral infections, and RNA polymerase catalyzes its replication and transcription activities in infected cell nuclei. Since it is highly conserved in all virus strains, RNA polymerase becomes a key target of anti-influenza virus agents. Although experimental studies have revealed the good inhibitory activity of endonuclease inhibitors to RNA polymerase, the mechanism is still unclear. In this study, the docking and molecular dynamics simulations have been performed to explore the interaction of three kinds of endonuclease inhibitors with the subunit (PA[SUB]N[/SUB]) of RNA polymerase. Our calculations indicate that all these endonuclease inhibitors can bind to the binding pocket of PA[SUB]N[/SUB], in which the electronegative oxygen atoms of the inhibitors form a chelated structure with the two Mn[SUP]2+[/SUP] cations of the active center. The most important interaction between these inhibitors and PA[SUB]N[/SUB] is electrostatic interaction. The electron density of the chelate oxygen atoms determines the magnitude of the electrostatic energy, and the chelated structure and orientation of inhibitors depend largely on the distance between the chelate oxygen atoms.
[h=4]KEYWORDS:[/h] Docking; Influenza virus RNA polymerase; Inhibitor; Molecular dynamics simulation
PMID: 28631174 DOI: 10.1007/s12539-017-0239-2