Chemdraw ultra 8

Molecular models between the S. aureus monofunctional GT (protein PDB code: 3HZS) and isatin analogues was performed using AutoDock Vina.^{52 (link)} All the 3D coordinates of isatin analogues were generated by ChemDraw Ultra 8.0 and energy minimized by Avogadro with Merck Molecular Force Field 94 (MMFF94).⁵³ The protein PDB and ligands MOL2 files were handled by reported procedures.^{54 (link)} The docking box contained the whole GT pocket.

In the current research, molecular
docking studies^{17 (link)−24 (link)} were performed to explore the binding modes of the ligand molecules
toward the target proteins PI3K and Akt. The crystal structures of
the targets were retrieved from the RCSB protein data bank.^{25 (link)} The target files were optimized by removing
the co-crystalized ligands, heteroatoms, and water molecules. In addition,
their energies were minimized using CHARM Force Field^{26 (link)} in Discovery Studio 3.5 Visualizer. Further, the 2D structures
of the prepared analogues were generated in cdx format (2D structures)
using ChemDraw Ultra 8.0 and then converted to sdf files (3D structures)
using the Open Babel GUI 2.4.1 tool.^{27 (link)} Furthermore,
the UFF force field^{28 (link)} in the PyRx tool
was used to minimize their energies. An in-house library of 12 ligand
molecules was generated for the docking. The in silico docking technique
was performed using PyRx—a virtual screening tool.²⁹ Grid maps of 25 × 25 × 25 ų were generated around the active site region of the target
proteins, resulting in nine conformers for each docked molecule, and
the minimum binding energy was selected for further study. The 2D
and 3D representations of docking results were visualized using Discovery
Studio 3.5. Finally, the drug-like properties of the newly prepared
molecules were calculated using mol inspiration, Swiss ADME, and Admet
SAR web tools.