Virtual screening of phospholipase PLA2G1B inhibitors based on molecular docking and pharmacophore

Phospholipase PLA2G1B is closely related to diet-induced obesity and related metabolic disorders. Studies have shown that some natural flavonoid compounds can inhibit phospholipase. An integrated molecular docking and pharmacophore strategy was used to screen PLA2G1B-targeted small molecule inhibitors. Molecular docking of five flavonoid compounds with PLA2G1B were possessed, and their interaction patterns were analyzed. A pharmacophore model based on common ligand molecular characteristics (HipHop) was established, which was used to screen small molecular compounds from ZINC database. The drug-likeness and pharmacokinetic properties (ADME) of the compounds with good fit values were predicted. The results show that kaempferol, luteolin, quercetin, myricetin and epigallocatechin gallate can bind PLA2G1B well, with the binding energies of −7.17~−6.17 kJ/mol. The pharmacophore model consisted of three hydrogen bond donors and one hydrogen bond receptor. By screening 10 897 small molecules in ZINC database, a total of 722 molecules with a hit rate of 6.6% were obtained. The 29 compounds with fit values higher than 2.5 are all meeting Lipinski's rule, and most of the compounds have good ADME parameters. These results can provide reference data for the design of PLA2G1B inhibitors and discovery of lead compounds.