In silico analysis of novel dipeptidyl peptidase-IV inhibitory peptides released from Macadamia integrifolia antimicrobial protein 2 (MiAMP2) and the possible pathways involved in diabetes protection

The aim of the present study was to screen novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides from Macadamia integrifolia antimicrobial protein 2 (MiAMP2) and evaluate the potential antidiabetic targets and involved signaling pathways using in silico approaches. In silico digestion of MiAMP2 with pepsin, trypsin and chymotrypsin was performed with ExPASy PeptideCutter and the generated peptides were subjected to BIOPEP-UWM, iDrug, INNOVAGEN and Autodock Vina for further analyses. Six novel peptides EQVR, EQVK, AESE, EEDNK, EECK, and EVEE were predicted to possess good DPP-IV inhibitory potentials, water solubility, and absorption, distribution, metabolism, excretion, and toxicity properties. Molecular dynamic simulation and molecular docking displayed that AESE was the most potent DPP-IV inhibitory peptide and can bind with the active sites of DPP-IV through hydrogen bonding and van der Waals forces. The potential antidiabetic targets of AESE were retrieved from SwissTargetPrediction and GeneCards databases. Protein-protein interaction analysis identified BIRC2, CASP3, MMP7 and BIRC3 to be the hub targets. Moreover, the KEGG pathway enrichment analysis showed that AESE prevented diabetes through the apoptosis and TNF signaling pathways. These results will provide new insights into utilization of MiAMP2 as functional food ingredients for the prevention and treatment of diabetes.