Gand complexes (5FNU_L61, 4XMB_41P, 5CG_51M and 4L7B_1VV). Results showed all other ligands had been stable with an RMSD value of much less than 1.25except 4L7B. Tyr334, Arg415, Ser508, Tyr525 and Tyr572 were identified to be pivotal for hydrophobic interactions whilst the amino acid residues essential for electrostatic interactions are Ser363,Arg483, Ser508, Gly530, Ser555 and Ser602 [12]. In one more investigation where esculetin’s anticancer properties was investigated in PANC-1, MIA PaCa-2 and AsPC-1 cell lines (pancreatic cells) by way of its anti-apoptotic and anti-proliferative prospective, it was reported that its anticancer properties was triggered by its antioxidant possible and when molecular docking simulation was implored to examine the interaction involving esculetin and Keap1, it was established that esculetin tightly binds Keap1 forming hydrogen bonds (Arg483 and Ala556) and hydrophobic interaction (Ser508, Ser555, Gln530, Gly462 and Ile461). Consequently, it was concluded that esculetin’s ARE activation possible by way of the inhibition of intracellular ROS and anti-cancer prowess ought to have already been orchestrated via the inhibition of Keap1 [13]. The inference from these researches might be that targeting the inhibition of Keap1 could be a therapeutic measure towards the amelioration/treatment of oxidative stress-induced ailments. As a result, within this investigation, we aim at exploiting various in silico solutions (ADMET profiling, bioactivity assessment, physicochemical properties, molecular docking and molecular dynamics simulation with Quantum mechanical-based PPARĪ³ Formulation Density Functional Theory) to indirectly investigate the atomistic mechanism surrounding the Nrf2 activating/ antioxidant capacity of different reported fifty (50) antioxidants by means of their Keap1 inhibitory prowess. The compounds with all the ideal keap1 inhibitory strength/stability may be subjected to further preclinical and clinical investigations that may result in their adoption as drugs/nutraceuticals for the management/treatment of oxidative stress-mediated diseases. 2. Materials and approaches two.1. Preparation of target protein Keap1 protein (PDB ID: 4ZY3) was applied because the target protein for this study. The X-ray crystallographic PDB structure of the target protein (PDB ID: 4ZY3) was obtained from the Protein Data Bank (https://www. rcsb.org/) (Figure 1) and was treated accordingly applying BIOVIA Discovery Studio Computer software (version 19.1), to stop unbidden molecular interactions through virtual screening. We defined the binding internet sites on the target receptors applying Computed Atlas for Surface Topology of Proteins (CASTp), along with the amino acid residues in the binding web-sites obtained were validated utilizing the binding pockets and residues reported experimentallyFigure 1. Structure of Kelch-like ECH connected Protein-1 (KEAP-1).for the target proteins applying X-RAY crystallography [14]. The amino acid residues reported by CASTp includes Arg326, Tyr334. Ser363, Gly364, Leu365, SSTR1 Storage & Stability Ala366, Gly367, Cys368, Val369, Arg380, Asn382, Asn414, Arg415, Ile416, Gly417, Val418, Gly419, Val420, Ile461, Gly462, Val463, Gly464, Val465, Ala466, Val467, Phe478, Arg483, Ser508, Gly509, Ala510, Gly511, Val512, Cys513, Val514, Ser555, Ala556, Leu557, Gly558, Ile559, Thr560, Val561, Ser602, Gly603, Val604, Gly605, Val606, Ala607, Val608. Autodock tool-1.five.6 plan [15] was used to decide the grids which involve the dimension and binding centre of 4ZY3 (-51.176, -3.868, -7.609) for (x, y, z) respectively. 2.two. Preparation of ligand.
