The in silico study of nutmeg seeds (Myristica fragrans Houtt) as peroxisome proliferator activated receptor gamma activator using 3D-QSAR pharmacophore modelling

Abstract

In this study, we created a pharmacophore models from a dataset of agonists for PPAR gamma receptor using the Catalyst/Hypogen module. A training set consists of 22 compounds activity range between 0.1 to 3,500 nM, were carefully selected. In previous study, molecular docking of macelignan against PPARγ binding pocket showed a free energy binding of -11.07 kJ/mol, interaction with the hydrophobic pocket (diphenyl pocket)(Celik et al., 2007), and a hydrogen bond network (His323, Tyr473, His449 and Ser289). The pharmacophore model (Hypo1), consisting of 5 features, i.e. one hydrogen bond acceptor (HBA), negative ionizable (NI), ring aromatic (RA) and two hydrophobics (HY) features, and one excluded volume. Hypo1 has the lowest total cost value (92.055), the highest cost difference (40.9316), the lowest RMSD (0.591049), and the best correlation coefficient (0.972949). Fourteen natural substances reported from nutmeg seeds (Myristica fragrans HOUTT.) were then mapped against Hypo1, and macelignan shows a fair fit value of 7.00102 with an estimated value of 1271.990 nM. This concludes, macelignant in nutmeg might have antidiabetic properties via PPARγ receptor activation.