Molecular Dynamics of SHBG-Ligand Complexes

The structural and dynamics changes in the complex of SHBG and the respective ligand with the dihydrotestosterone, aminoglutethimide, and hexaconazole were assessed. The duration of the MD simulation was 30 ns in triplicate using GROMACS 2021 software, (Groningen, The Netherlands) and the Charmm 27 force field was applied to all atoms [20 (link)]. SHBG and the respective complex were solvated by simple point charge (SPC) water molecules. In addition, counter ions (Cl or Na) to neutralize the protein [21 (link)] were applied. Furthermore, van der Waals contacts between the atoms were eliminated by energy minimization. The complex was equilibrated in two phases. The next step was a constant number of particles, volume, and temperature (NVT) ensemble with endothermic and exothermic processes, which was exchanged with the thermostat, followed by a constant number of particles, pressure, and temperature (NPT) ensemble at 300 K with constant pressure. The linear constraint solver (LINCS) algorithm was then used to constrain the covalent bonding approach. Finally, 30 ns of MD was run to examine the stability of each system. MD was performed 3 times to verify the MD findings [10 (link),11 (link),12 (link),13 (link)]. The details related to the set-up of MD simulations are given in Table 4.