The X-ray crystal structure of SHBG (1D2S) was acquired from Protein Data Bank (PDB). The native ligands are dihydrotestosterone PUBChem Id 10635 and aminoglutethimide PUBChem Id 2145, which were used to understand the interaction pattern of hexaconazole 66461.
For molecular docking analyses, hexaconazole was docked with SHBG using the program AutoDock version 4.2 (San Diego, CA, USA) [18 (link)]. For the precise molecular interaction analyses, all crystallographic water was removed from SHBG (1D2S) protein and energy was minimized by Swiss PDBViewer, and the active site was obtained from PDBSUM. In addition, ligand energy was minimized by chimera (dihydrotestosterone PUBChem Id 10635, aminoglutethimide PUBChem Id 2145, and hexaconazole 66461). Before docking was run with AutoDock version 4.2, the structure of the target was optimized by Kollman with combined charges and solvation parameters. After this, hydrogen was added to SHBG in ideal geometry, and torsions were fixed. In addition, the protein’s van der Waals well depth was assigned, and the files were saved in PDBQT format. For the generation of grid parameters, AutoDock tools were used, and grid parameter files (GPFs) and docking parameter files (DPFs) were generated. For ligand and protein interaction analyses, the Lamarckian genetic algorithm [18 (link)] was applied. A total of 50 different poses were used to obtain the binding score [19 (link)]. The best complex was taken for molecular dynamics (MD) studies on the basis of a high binding score. For the visualization of the complex, Discovery Studio 16, molecular visualization software (Biovia, 2019) was used. In addition, molecular interaction analysis of hexaconazole-similar azole fungicide compounds with 1D2S was performed to understand the chemical feature of hexaconazole.
For molecular docking analyses, hexaconazole was docked with SHBG using the program AutoDock version 4.2 (San Diego, CA, USA) [18 (link)]. For the precise molecular interaction analyses, all crystallographic water was removed from SHBG (1D2S) protein and energy was minimized by Swiss PDBViewer, and the active site was obtained from PDBSUM. In addition, ligand energy was minimized by chimera (dihydrotestosterone PUBChem Id 10635, aminoglutethimide PUBChem Id 2145, and hexaconazole 66461). Before docking was run with AutoDock version 4.2, the structure of the target was optimized by Kollman with combined charges and solvation parameters. After this, hydrogen was added to SHBG in ideal geometry, and torsions were fixed. In addition, the protein’s van der Waals well depth was assigned, and the files were saved in PDBQT format. For the generation of grid parameters, AutoDock tools were used, and grid parameter files (GPFs) and docking parameter files (DPFs) were generated. For ligand and protein interaction analyses, the Lamarckian genetic algorithm [18 (link)] was applied. A total of 50 different poses were used to obtain the binding score [19 (link)]. The best complex was taken for molecular dynamics (MD) studies on the basis of a high binding score. For the visualization of the complex, Discovery Studio 16, molecular visualization software (Biovia, 2019) was used. In addition, molecular interaction analysis of hexaconazole-similar azole fungicide compounds with 1D2S was performed to understand the chemical feature of hexaconazole.
Free full text: Click here
