Table 3.
NSC765598 and standard drug comparative docking profile against mTOR/MAP2K/EGFR.
| mTOR | MAP2K | EGFR | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NSC765598 | DIS (Ӑ) | Dactolisib | DIS (Ӑ) | NSC765598 | DIS (Ӑ) | Mirdamatinib | DIS (Ӑ) | NSC765598 | DIS(Ӑ) | Gefitinib | DIS (Ӑ) | |
| ΔG=(Kcal/mol) | −8.8 | −9.2 | −7.6 | −6.5 | −11.0 | −6.8 | ||||||
| Conventional | ARG2224 | 2.76 | GLN1937 | 2.19 | ARG129 | 2.91 | ARG129 | 2.78 | GLU762 | 2.42 | MET793 | 2.32 |
| H-bond | VAL2227 | 2.53 | ARG2224 | 2.35 | TYR174 | 2.85 | GLU142 | 2.94 | CYS792 | 2.29 | ||
| GLN1937 | 2.83 | |||||||||||
| C-H bond | GLN2200 | 3.27 | ARG141 | 3.1 | ASP800 | 3.71 | ||||||
| GLN791 | 3.50 | |||||||||||
| Halogen bond | GLN1937 | 3.36 | ASP149 | 3.20 | ASP149 | 3.65 | ASN842 | 3.24 | ASP855 | 3.09 | ||
| Val2227 | 3.30 | GLU145 | 3.09 | GLU145 | 3.51 | ARG841 | 3.40 | |||||
| GLU142 | 3.21 | ASP855 | 3.52 | |||||||||
| π -anion | ASP2145 | 4.82 | ASP149 | 3.96 | ASP149 | 3.99 | ||||||
| GLU142 | 4.59 | |||||||||||
| π -cation | ARG2224 | 4.27 | ||||||||||
| π –sulfur | 3.70 | MET790 CYS797 |
5.43 3.63 |
|||||||||
| π -alkyl | PRO2146 | ARG141 | ALA743 | |||||||||
| LEU1900 | VAL726 | |||||||||||
| LEU2204 | ||||||||||||
| π -π stacked | PHE723 | |||||||||||
| Amide-π stacked | LEU1936 | LEU1936 | ||||||||||
| GLU142 | LEU844 | 5.49 | LEU844 | |||||||||
| π-sigma | LEU718 | |||||||||||
| Van der waal forces |
ASP1933, | ALA1971 | GLN312 | VAL182 | ARG858 | GLY719 | ||||||
| PRO21146, | ILE1939 | LYS179 | ALA181 | LYS745 | LYS745, | |||||||
| ALA2226, | GLU2196 | ILE146 | TYR174 | LEU788 | PHE723, | |||||||
| GLU2196, | MET2199 | ALA181 | ILE146 | THR854 | MET790, | |||||||
| MET2199, | GLN2200 | LEU183 | ARG133 | ARG841, | ||||||||
| PRO1940 | GLY2203 | HIS96 | PHE138 | ASN842, | ||||||||
| GLY2203 | THR2207 | LYS149 | THR854 | |||||||||
| LEU2204 | ASN2147 | GLN312 | LEU792, | |||||||||
| LEU1900 | ARG141 | GLY796, | ||||||||||
| ASN1899 | PRO794, CYS797 | |||||||||||
| Hydrophobic Interactions | sLEU1936 | 3.89 | LEU1900 | 3.31 | ARG141 | 3.99 | LEU50 | 3.84 | PHE723 | 3.74 | LEU718 | 3.77 |
| GLN1937 | 3.73 | PRO2146 | 3.63 | GLU142 | 3.70 | VAL58 | 3.67 | PHE723 | 3.66 | LEU718 | 3.70 | |
| GLN1937 | 3.58 | GLU2196 | 3.97 | GLU142 | 3.64 | MET121 | 4.0 | PHE723 | 3.88 | LEU718 | 3.90 | |
| GLN2200 | 3.61 | GLN2200 | 3.77 | GLU145 | 3.84 | LEU173 | 3.51 | LEU844 | 3.42 | VAL726 | 3.59 | |
| THR186 | 3.64 | LEU844 | 3.64 | VAL726 | 3.59 | |||||||
π –sulfur: π-electron cloud between the Aromatic rings of ligands and lone pair of electron cloud of sulfur atom in the receptors; π -π stacked: π-electron cloud between the Aromatic rings, π -π T-shaped: T shaped π-electron cloud between the Aromatic rings, π –alkyl; π-electron cloud between the Aromatic ring of ligand and alkyl group of ligand.