Q2. What have the authors stated for future works in "Inhibition of viral group-1 and group-2 neuraminidases by oseltamivir: a comparative structural analysis by the screwfit algorithm" ?
Although answering to this kind of questions is not possible through a static analysis, and would require kinetic experiments and dynamic simulations, it is reasonable to assume that, through patterns of function conserving mutations, viral proteins explore not only structural possibilities, but also dynamical repertoires. Additionally, it would be interesting to have further comparative molecular dynamics simulations of NA1 ( or NA8 ) and NA9, with the aim of checking if phylogenetical distances correspond to different dynamical behaviors.
Q3. What are the two classes of antiviral drugs available against flu viruses?
Two classes of antiviral drugs are available against flu viruses: the inhibitors ofthe ion channel activity of the M2 membrane protein (i.e., amantadine and rimantadine), and the NA inhibitors (i.e., oseltamivir (Tamiflu®) and zanamivir (Relenza®)).
Q4. What is the antigenicity of the two surface glycoproteins?
The antigenicity of the two surface glycoproteins hemagglutinin (H) and neuraminidase (NA) is used to cluster type-A flu viruses into subtypes: 16 for H (H1-H16) and 9 for NA (NA1-NA9).
Q5. What is the purpose of the ScrewFit analysis?
The ScrewFit analysis, although related only on backbone conformational changes, proved to be useful in the evaluation and refinement of crystallographic results.
Q6. What is the classification of the flu viruses?
Flu viruses, belonging to the Orthomyxoviridae family, are classified as A, B, and C, on the basis of the antigenic differences of their nuclear and matrix proteins,; all avian flu viruses belong to type-A.
Q7. What is the extent of the change in the oseltamivir-bound?
The extent of this change (~ 0.1) shows that peptide planes between residue Asn247 and Gly248 adopt a β-turn-like configuration in the closed oseltamivir-bound NA1.
Q8. What is the t component of the distance vector t = CC'?
Here t⊥ is the component of the distance vector t = CC' , which is orthogonal to the rotation and translation axis n of the screw motion, and φ is therotation angle.
Q9. How does the kink affect the helix radius?
Tthe positive change in the straightness (close to one), which indicates a kink into the local axis of rotation between residues Asn247 and Gly248.
Q10. What is the role of the regions flanking the active site in the structure of NAs?
From a structural point of view, present results raise the basic question whether group-1NAs are more rigid than group-2 enzymes in oseltamivir binding and which role the variability of the regions flanking the active site plays in respect to the flexibility of NAs.
Q11. What is the difference between the open and closed conformations?
In the closed conformation, the peptide planes of residues Leu140-Arg152 tend to be more distant from the local rotation axis of the screw motion, indicating a change from a flat to a curled conformation.