Pyrimido[4,5-b]indole Derivatives Bearing 1, 2, 4-oxadiazole moiety as MDM2 Inhibitor Candidates in Cancer Treatment - supplementary_information .docx

  

Figure S1. Superimposed RMSF graph of MDM2 in complex with the studied compounds; 12c (orange), 12b (yellow) and 12d (green), as well as Nutlin-3a as known ligand (blue), obtained from 50 ns MD simulation.

  

Figure S2. Superimposed RG graph of MDM2 in complex with the studied compounds; 12c (orange), 12b (yellow) and 12d (green), as well as Nutlin-3a as known ligand (blue), obtained from 50 ns MD simulation

  

Figure S3. Protein interactions with the three studied compounds, 12c, 12b, 12d, and Nitlin3a monitored throughout the simulation. These interactions can be clustered by type and summarized, as shown in the plots. (A) Categorization of protein-ligand interactions into four types: H-bonds, hydrophobic, ionic, and water bridges. (B) Hydrophobic contacts of the ligand into the p53 binding site on MDM2 over the course of the trajectory. (C) The representation of the total number of specific contacts that the protein makes with the ligands over the course of the trajectory (D) a timeline representation of the interactions and contacts of panel A (H -bonds, hydrophobic, ionic, water bridges). Some residues make more than one specific contact with the ligand, which is represented by a darker shade of orange, according to the scale to the right of the plot

  

Figure S4. 2D schematic of the detailed atomic interactions of three studied compounds; 12c, 12b and 12d, with the protein residues monitored throughout the simulation. In each case, interactions that occur more than 5.0% of the simulation time in the selected trajectory are shown.

  

Figure S5: 2D schematic of the detailed atomic interactions of the known ligand, Nutlin-3a, with the protein residues monitored throughout the simulation. In each case, interactions that occur more than 5.0% of the simulation time in the selected trajectory are shown

1H NMR & 13C NMR compopund 5d-12d