Figure 1.
Illustratively showing the binding mode of the PB2 cap binding domain in the presence of the cap analog m7GTP.
The protein structure was shown in a ribbon diagram, while m7GTP is in ball-and-stick representations. The secondary structure elements of the PB2 cap binding domain are labeled with α-helices in red and β-strands in yellow. The cap analog m7GTP is colored according to its atomic types.
Figure 2.
Energy contributions (kcal/mol) for each residue to the binding free energies of the PB2-m7GTP complex.
Only the residues that have positive contributions to the binding free energies are listed in this figure. Among these residues, His357 has the most contributions owe to having both hydrogen bonding and π-π stacking interactions with the cap analog m7GTP.
Figure 3.
A 2D snapshot from MD simulations to show the binding interactions of the cap analog m7GTP with the key residues in the cap binding domain.
The hydrogen bond is shown in green dashed line with the arrow pointed to the hydrogen acceptor. The π-π stacking and π-cation interactions are presented in green benzene ring symbol. The residues without any dashed line or benzene ring symbol have only van der Waals interactions with m7GTP.
Table 1.
Binding free energies (kcal/mol) of m7GTP and other ligands calculated from both MM-PB/SA and MM-GB/SA.
Table 2.
Detailed information for the important hydrogen bonding interactions between the PB2 cap binding domain and cap analog m7GTP.
Figure 4.
The cap-binding pockets for the influenza A virus PB2 subunit.
The residues around the cap-binding pocket are colored so that those aromatic amino acids forming the cap sandwich around the cap analogue m7GTP are in blue, those binding the functional groups of the guanine residue are in orange, those stabilizing the 7-methyl group are in yellow and those binding the triphosphate moiety are green.