Moe 2008

First, the molecular structures of 566 organic marketed drugs with common ADRs were downloaded from the Pubchem database based on their names and checked one by one. After removing multi-compound drugs, a total of 497 organic monomer drugs remained. Then, they were put into the Molecular Operating Environment software (MOE2008.10, Chemical Computing Group Inc., Montreal, Canada), to be subjected to the energy minimization of 3D structures. Subsequently, stochastic conformation search was performed to optimize their conformer structures. Then, a total of 327 diverse descriptors of optimized structures were calculated by utilizing the QSAR module of MOE. These 327 descriptors consisted of 184 2D molecular properties, 86 i3D molecular properties and 10 x3D structural information, which may be redundant and irrelevant for QSAR development. Thus, the constant or almost constant descriptors for all molecules were first deleted and then a pairwise correlation analysis was conducted to remove one of inter-correlated descriptors (with a correlation coefficient value greater than 0.95) [17 (link)]. Finally, a total set of 130 descriptors remained and was used for QSAR modeling.

All modelling experiments were conducted with MOE programs running on PC computer (MOE 2008.10 of Chemical Computing Group. Inc, Montreal, QC, Canada)⁶⁷ . Starting coordinates of the X-ray crystal structure of EGFR enzyme in complex with eroltinib (PDB code 1M17) is obtained from the RCSB Protein Data Bank. All the hydrogen was added and enzyme structure was subjected to a refinement. The docking methodology was similar to that described in our previous reports^{5 ,68–70} (link).

The molecular docking study was performed on the identified compounds (phenolic extract) towards the apoptosis inhibitor, Bcl-2 (PDB: 4IEH), to elucidate their cytotoxic and apoptotic activity profiles. The molecular docking studies were carried out using the MOE 2008–10 (Chemical Computing Group, Canada) as the computational software. The protein structure complexed with the co-crystallized ligand was easily accessible from the Protein Data Bank. Routine work concerning receptor and ligand preparation and molecular docking was carried out as previously published [63 (link),64 (link)].

Molecular docking analysis was performed using the Molecular Operating Environment (MOE) 2008.10 program (Chemical Computing Group Inc., Sherbrooke St. W, Montreal, QC, Canada). TRI-BE ligand design was performed using the Corina program (Molecular Networks GmbH Computerchemie, Nürnberg Germany). FAK and Src were obtained from the Protein Data Bank (PDB): 1MP8 crystal structure of focal adhesion kinase (FAK) (PDB https://doi.org/10.2210/pdb1MP8/pdb) and 1FMK crystal structure of human tyrosine-protein kinase C-Src (PDB https://doi.org/10.2210/pdb1FMK/pdb). The generation of the respective TRI-BE conformers to be evaluated was performed using Moe 2008.10. The proteins of interest, FAK and Src, were prepared for coupling using Moe 2008.10 by eliminating water molecules, protonating, and selecting the force field. Molecular coupling of TRI-BE with FAK or Src was performed by selecting the three highest-affinity E-Scores. The 2D and 3D images of the interaction site between the involved amino acids and the TRI-BE ligand were generated.

The molecular docking technique was performed by using MOE 2008.10, from the Chemical Computing Group Inc.⁴⁵ in accordance with previously established methods¹⁸ (link)^,40–42 (link).

Molecular Operating Environment (MOE) 2008.10 (Chemical Computing Group Inc., Quebec, Canada, 2008) was used to perform the molecular docking studies. A Gaussian contact surface was drawn around the binding sites enclosing the van der Waals surface. Docking studies were undertaken to assess the binding free energy of the complexes inside the DNA. The docking scores were first acquired utilizing the London dG scoring function in the MOE software, and then were improved using two unrelated refinement methods. The Grid-Min pose and Force-Field were employed to confirm that the refined poses of the complexes were geometrically correct. Bond rotations were allowed, and the best five binding poses were then examined. The docking poses of the ethidium bromide, 4, 5a, 5b and the co-crystallized structure of the B-DNA were docked (RSCP PDB code: 1BNA). RMSD values were used to assess the best binding pose.