Figure 1.
A close-up view for the binding site of HA1 (PDB ID: 3AL4).
The binding pocket is defined by those residues that have at least one heavy atom with a distance 5 Å from the NAG ligand [37]. The four loops (loop1, loop2, loop3, and loop4) that play an important role in interacting with the ligand are represented by round ribbons of four different colors as well as their key residues Ser92, Glu72, Pro143, and Arg227, respectively. The motions of such four residues were monitored during the molecular dynamic simulation. The docked poses for ZINC01602230, Neo and Neo6 are shown with the stick model colored in purple, yellow and dark green, respectively.
Figure 2.
The flowchart to show the inhibitor design process.
The core1, core2, core3 and core4 were the key fragments for improving the ligand binding affinity.
Figure 3.
The structures and docking scores list for the top ten compound candidates modified from Neo and ZINC01602230.
Figure 4.
A close view to show the interaction of the receptor with the docked Neo6.
(A) The yellow dotted lines indicate the H-bond interactions of the receptor with Neo6. (B) The molecular surface is shown around the binding site of 3AL4; the hydrophobic surface is colored in green and the hydrogen bond surface in purple. See the text for further explanation.
Figure 5.
Analysis of molecular dynamics simulations.
(A) The RMSD for all backbone atoms of the Neo6-HA1 system (green) and the HA1 system (red). (B) The RMSF for side-chain atoms of the Neo6-HA1 system (green) and the HA1 system (red). The curves associated with Loop1, Loop2, Loop3, and Loop4 are colored orange, light blue, dark blue, and maroon, respectively.