Vina 1

Molecular docking of the ethylene was implemented in the LeETR2_1–131 relaxed model. The two cofactor monovalent copper ions were placed around the copper binding sites, C64 and H68 of LeETR2_1–131. The receptor of LeETR2_1–131 was protonated using the REDUCE algorithm and prepared using the prepare-receptor algorithm, all from the ADFR suite [17 (link)]. The ethylene was protonated and prepared using the mk-prepare-ligand algorithm from the ADFR suite [17 (link)] (ADFR suite. Available online: https://ccsb.scripps.edu/, accessed on 2 December 2021). The Autodock Vina 1.2.2 software [18 (link)] (Autodock Vina 1.2.2. Available online: https://github.com/ccsb-scripps/AutoDock-Vina, accessed on 2 December 2021) was utilized for molecular docking, in which vinardo scoring function parameters were selected. The grid dimensions were set to 30 × 30 × 30 Å to allow enough regions to cover the copper binding sites, where the coordinate of the grid center was set to 0 × 0 × 5.844 Å (LeETR2_1–131). In addition, the default values were used for other parameters with the exhaustiveness of 32 for better searching space. The best-fitted poses from docking models were used for further MD simulations.

To analyze the binding affinities and modes of interaction between IPA and AhR, AutodockVina 1.2.2, a silico protein-ligand docking software, was employed (http://autodock.scripps.edu/) (Morris et al. 2008 (link)). The molecular structure of IPA (PubChem CID: 3744) was retrieved from PubChem Compound (https://pubchem.ncbi.nlm.nih.gov/) (Wang et al. 2017 (link)). The 3D structure of AhR (PDB ID: 5NJ8; resolution: 3.3 Å) was downloaded from the PDB (https://www.rcsb.org/). For docking analysis, both protein and molecular files were converted into PDBQT format with all water molecules excluded and polar hydrogen atoms added. The grid box was placed in the center to cover the protein’s domain and accommodate free molecular movement. Molecular docking and visualization were performed by Autodock Vina 1.2.2.
The molecular functional network map of canonical pathways, including physical interactions, co-expression, predicted networks, co-localization, genetic interactions, pathway and shared protein domains of AhR and NF-κB were analyzed using GeneMANIA (http://genemania.org/) (Warde-Farley et al. 2010 (link)).

To investigate the binding affinities and interaction patterns of the drug candidates with their targets, we utilized AutoDock Vina 1.2.2, a software designed for in silico protein–ligand docking (24 (link)). The molecular structure of resveratrol was obtained from the PubChem Compound database (https://pubchem.ncbi.nlm.nih.gov/) (25 (link)). AlphaFold 2 was used to generate the 3D coordinates for ALKBH1. Before docking analysis, all proteins and ligand files were prepared by converting them into PDBQT format. This preparation involved the removal of water molecules and the addition of polar hydrogen atoms to ensure accurate docking simulations. The docking grid box was strategically positioned to encompass the target protein’s domain, allowing for unhindered molecular movement within the simulation. The dimensions of the grid box were set to 30 Å × 30 Å × 30 Å, with a grid point spacing of 0.05 nm to capture detailed interaction data. The molecular docking studies were conducted using AutoDock Vina 1.2.2 (http://autodock.scripps.edu/).

To analyze the binding affinities and modes of interaction between the drug candidate and their targets, AutodockVina 1.2.2, a silico protein–ligand docking software was employed.
³¹ (link) The molecular structures of LDHB were retrieved from PubChem Compound (https://pubchem.ncbi.nlm.nih.gov/).
³² (link) The 3D coordinates of Stathmin (PDB ID, 7DBK; resolution, 2.5 Å) were downloaded from the PDB (http://www.rcsb.org/). To conduct the docking analysis, the protein and molecular files underwent conversion into PDBQT format, excluding all water molecules and adding polar hydrogen atoms. The grid box was then centered to encompass the domain of each protein and allow sufficient space for molecular movement. The dimensions of the grid box were set at 30 Å × 30 Å × 30 Å, with a grid point distance of 0.05 nm. The molecular docking studies were carried out using Autodock Vina 1.2.2 (http://autodock.scripps.edu/).

To analyze the binding affinities and modes of interaction between the drug candidate and their targets, AutodockVina 1.2.2, a silico protein–ligand docking software was employed [28 (link)]. The molecular structures of Ropivacaine hydrochloride (PubChem CID: 175804) was retrieved from PubChem Compound (https://pubchem.ncbi.nlm.nih.gov/) [29 (link)]. The PDB format files of the AKT1(PDB ID: P31749) were generated from the AlphaFold Protein Structure Database (https://alphafold.ebi.ac.uk/) [30 (link)]. For docking analysis, all protein and molecular files were converted into PDBQT format with all water molecules excluded and polar hydrogen atoms were added. The grid box was centered to cover the domain of each protein and to accommodate free molecular movement. The grid box was set to 30 Å × 30 Å × 30 Å, and grid point distance was 0.05 nm. Molecular docking studies were performed by Autodock Vina 1.2.2 (http://autodock.scripps.edu/).