Maestro v11

In this test, the antioxidant activity was conducted to examine the, in silico, inhibitory potency of Lavandula dentata EO against nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase as an important antioxidant marker. All compounds identified in the studied EO were downloaded from the PubChem database in SDF format. Afterward, the Maestro 11.5 of the Schrödinger Software was used to prepare chemicals using the OPLS3 force field and the LigPrep tool. At a pH of 7.0 ± 2.0, ionization states generated 32 stereoisomers per ligand. The NADPH oxidase crystal structure in the Protein Data Bank was accessible through the following PDB ID : 2CDU. The structure was prepared and refined using the Protein Preparation Wizard of Schrödinger-Maestro v11.5. The minimization of the structure was conducted using the OPLS3 force field. The receptor grid was set at the following coordinates: X = 0.395, Y = 10.379, and Z = 53.876, where the volumetric spacing performed was 20 × 20 × 20. SP flexible ligand docking was carried out in glide of Schrödinger-Maestro v 11.5 [15 (link)].

Previously reported protocol was used for the molecular docking simulations (16 (link)) by using Maestro v11.1 software (Schrödinger, LLC, New York, NY). The structure of sitravatinib after preparation by LigPrep v4.1 to simulate the low-energy pose was subjected to the Glide XP (extra precision) docking default protocol (Schrödinger, LLC, New York, NY) with a pre-prepared cryo-EM structure of the human ABCG2 model (PDB code: 6ETI). The human ABCG2 protein model was confined to the docking grid at the drug-binding cavity by selecting specific amino acids that were deemed to be involved in specific interactions (25 (link)). The following induced-fit docking (IFD) was generated based on the best scored results from the Glide XP analysis. The docked sitravatinib-ABCG2 complex simulated based on IFD was then subjected to another 10 ns molecular dynamic (MD) simulation using a previously reported default protocol (26 (link)). The docking scores were calculated and reported as kcal·mol⁻¹ and the highest-scoring result was used for further graphical analysis.

Molecular docking is a valuable computational tool, providing valuable insights into the pharmacological activities of natural products by elucidating the potential binding modes and affinities with target molecules. Two compounds (beta-sitosterol and sitosterol) were selected for computational analysis. The docking analysis was monitored as per Madhavi Sastry et al. (2013) (link). Schrödinger Maestro (v11.1, 1540 Broadway, New York, United States) was used to optimize each phytochemical’s three-dimensional (3D) structure. The 3D structures of the following proteins were retrieved from the Protein Data Bank (https://www.rcsb.org/; Berman et al., 2000 (link)): urate oxidase (PDB: 1R4U) (Retailleau et al., 2004 (link)), glutathione reductase (PDB: 3GRS) (Karplus and Schulz, 1987 (link)), pancreatic alpha-amylase (PDB: 3BAJ) (Maurus et al., 2008 (link)), potassium channel (PDB ID: 4UUJ) (Lenaeus et al., 2014 (link)), human gamma-aminobutyric acid receptor (PDB ID: 4COF) (Miller and Aricescu, 2014 (link)), human serotonin transporter (PDB ID: 5I6X) (Coleman et al., 2016 (link)), and chimeric protein of 5-HT1B-BRIL (PDB ID: 4IAQ) (Wang et al., 2013 (link)).