Insilico activity
Molecular modeling studies using the automated docking protocol into the
ATP-binding site of amyloid beta protein at 2.0 A° resolution (PDB code:
2g63), following a flexible rigid/ligand-receptor docking protocol was
performed. Maestro 9.4 was used for estimation of binding pose presented
in supplementary figure 3. As can be seen, the docking program
positioned compounds rutin makes a hydrogen bond with ser209, glu205,
glu206, tyr662, tyr547, and arg125 and also makes pi-pi stacking with
tyr547 and arg125against backbone of DPP4 protein. Herein, rutin gives
better interaction with a backbone of DPP4protein due to its hydrophilic
interaction and pi-pi interaction with the amino acid residue of the
DPP4 protein(Chen and Zhi, 2001; Gray et al., 2003). We further validate
the interaction by superimposing our ligand (rutin) with glibenclamide
ligand and found that the binding orientation of our ligand and
glibenclamide was similar as above. The binding affinity of ruin with
the DPPIV protein was found -11.25 kcal/mol and glibenclamide showed the
docking affinity -6.053 kcal/mol, respectively (Supplementary table 3).
As can be seen, the docking program positioned compounds rutin makes a
hydrogen bond with thr137, glu380, asn415, asn288 and asn411 against the
backbone of GLUT1 protein (Supplementary figure 4). Herein, rutin gives
better interaction with a backbone of GLUT1 protein because it is
exhibiting hydrophilic interaction and pi-pi interaction with the amino
acid residue of the GLUT1 protein. We further validate the interaction
by superimposed our ligand (rutin) with glibenclamide ligand and
observed that binding orientation of our ligand was similar to the ruin.
The binding affinity of rutin with the GLUT1 protein was found -13.101
kcal/mol and glibenclamide showed the docking affinity -8.29 kcal/mol,
respectively (Supplementary table 3).
As can be seen, the docking program positioned compounds rutin makes a
hydrogen bond with glu259 against the backbone of PPARY protein. Herein,
rutin gives better interaction with a backbone of PPARY protein because
it is exhibiting hydrophilic interaction and pi-pi interaction with the
amino acid residue of PPARY protein (Supplementary figure 5). We further
validate the interaction by superimposed our ligand (rutin) with
glibenclamide ligand and observed that binding orientation of our ligand
was similar to the rutin. The binding affinity of rutin with the DPPIV
protein was found -12.849 kcal/mol and glibenclamide showed the docking
affinity -6.732 kcal/mol, respectively (Supplementary table 3).