Ts of depressionIngredients of CCHPdepressionNetwork construction herb-compound-target network of CCHP protein-protein
Ts of depressionIngredients of CCHPdepressionNetwork construction herb-compound-target network of CCHP protein-protein interaction network of CCHP in treating depression herb-compound-target network Network analysis GO and KEGG enrichment evaluation KEGG enrichment analysis GO enrichment analysis Target-Pathway network evaluation Target-Pathway network analysis Molecular docking protein-protein interaction network Intersection of targets of depression and CCHPcore compoundsMolecular docking of core compounds and core targets Docking models of core compounds and core targetscore targets Molecular dynamics simulations0.six 0.5 RMSD (nm) 0.4 0.3 0.2 0.1 0 ten 0.228.027 20 30 Time (ns) 40 50 0.194.Molecular dynamics simulationsMolecular Mechanics-Poisson Boltzmann Surface Area6hhi_G4N 6hhi_QuercetinBinding free energyRMSDFigure 1: Workflow for the network pharmacology-based study of CCHP in treating depression.ChemBio 3D Software to export the 3D structures. AutoDockTools 1.five.six Software program was then employed to add charge values and export the structures in pdbqt format. Second, the 3D structures in the core targets have been acquired in the RCSB PDB database (rcsb/) [35] and deleted water along with other ligands. AutoDockTools 1.5.6 was utilized to add hydrogen and charges and convert the structures into pdbqt format. Finally, AutoDock Vina 1.1.2 was utilized to perform molecular docking and analyze the results [36]. Docking outcomes had been visualized and analyzed using PyMOL 1.7.2.1 and Ligplus 2.2.4. e docking of core compounds and targets with lower docking energies had stronger binding forces. two.10. Molecular Dynamics Simulations. Due to the fact AKT1 (PDB ID: 6hhi) was the core target and quercetin was the core compound, the docking conformation of 6hhi andquercetin, which had low binding power, was selected as the initial conformation for molecular dynamics (MD) simulations. G4N, the primitive ligand of 6hhi, was utilised as the positive manage. MD simulations had been performed utilizing the GROMACS 2018.4 program [37] under continuous temperature and stress and periodic boundary situations. Amber99 SB all-atom force field and TIP3P water model had been applied [38]. Through MD simulations, all bonds involving hydrogen atoms had been constrained applying the LINear Constraint Solver (LINCS) algorithm [39] with an integration step of 2 fs. Electrostatic interactions had been calculated utilizing the particle mesh Ewald (PME) technique [40]. e nonbonded interaction cutoff was set to 10 A and updated each and every 10 methods. e V-rescale temperature coupling strategy [41] was applied to handle the PARP Activator MedChemExpress simulation temperature at 300 K, along with the Parrinello ahman method [42] was employed to manage the stress at 1 bar.four Initially, energy minimization was performed in the two systems SIRT2 Inhibitor custom synthesis employing 5000 methods of steepest descent algorithm with all the convergence of power minimization of 100 kJ/mol/nm to get rid of excessive interatomic contact. en, the systems had been heated steadily from 0 to 300 K within the canonical ensemble (NVT) and equilibrated at 300 K for 1000 ps within the continuous pressure-constant temperature ensemble (NPT). Finally, the systems were subjected to MD simulations for 50 ns and also the conformation was preserved just about every 10 ps. e simulation results had been visualized employing the GROMACS embedding plan and visual molecular dynamics (VMD). 2.11. Calculation of Binding No cost Energy. e molecular mechanics Poisson oltzmann surface area (MMPBSA) system [43] was utilised to calculate the binding energy involving substrate modest molecules and proteins i.
