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).