Computational protocol: O-prenylated 3-carboxycoumarins as a novel class of 15-LOX-1 inhibitors

Similar protocols

Protocol publication

[…] The desired structures were drawn in ChemDraw Ultra 8.0. [] Then the 2D structures were exported to the HyperChem 8.07 software and geometrically optimized using classic MM+ (RMS gradient = 0.05 kcal mol-1) [] and semi-empirical AM2 methods (convergence limit = 0.01; Iteration limit = 50; RMS gradient = 0.05 kcal mol-1; Polak-Ribiere optimizer algorithm) to simulating of the 3D structures.Crystal structure of Rabbit 15-lipoxygenase-1 (Rabbit 15-LO-1) complex with RS75091 was retrieved from RCSB Protein Data Bank (PDB entry: 2P0M). [...] The ligand of Rabbit 15-LO-1 3D structure was omitted. Then the Fe was modified to FeIII-OH, geometrically optimized by MM+ method in HyperChem8.0 and outputted in pdb format for docking process [].Docking of the minimized structures into the active site of 2P0M was down by AutoDock 4.2. [] The torsion angles of the ligands were identified, bond distances were edited, hydrogens and solvent parameters were added to the enzyme 3D structure. Partial atomic charges were then assigned to the macromolecule as well as ligands (Gasteiger for the ligands and Kollman for the protein).The docking regions of the enzyme were defined by considering Cartesian chart -53.10, 166.95 and 35.82 as the central of a grid size with 68, 52 and 66 points in X, Y and Z axis. The docking parameter files were generated using Lamarckian genetic algorithm Parameters (GALS) while number of generations and maximum number of energy evaluations was set to 200 and 2,500,000, respectively. The 200 docked complexes were clustered with a root-mean-square deviation tolerance (RMSD) of 2.0 Å. Docking results were submitted to Accelrys Discovery Studio v3.1 [] for further evaluations. […]

Pipeline specifications

Software tools ChemDraw, AutoDock
Applications Drug design, Protein interaction analysis
Chemicals Coumarins