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

Abstract

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.

An updated review on food‐derived bioactive peptides: Focus on the regulatory requirements, safety, and bioavailability

“…As a result, Caco-2 peptide permeability was projected to be low, ranging from −6.655 to −5.191. Zhao et al (2021) also used an iDrug to investigate DPP-IV inhibitory peptides extracted from Macadamia integrifolia antimicrobial protein 2 (MiAMP2) and its in silico ADMET properties. Six peptides, comprising EVEE, EQVR, AESE, EEDNK, EECK, and EQVK, were expected to have high water solubility and excellent ADMET features, such as good Caco-2 permeability (>10-6 cm/s) and high HIA (probability > .5), according to the computational study.…”

Proteomics Characterization of Food-Derived Bioactive Peptides with Anti-Allergic and Anti-Inflammatory Properties

“…Furthermore, anti-inflammatory peptides from Baiju vinasse [ 133 ], sturgeon muscle [ 134 ], and amaranth [ 135 ] were determined by mass spectrometry techniques. Anti-inflammatory peptides were obtained from chickpea [ 136 ], pine needles [ 137 ], buffalo casein [ 138 ] and Satureja khuzistanica leaves [ 139 ], and identified by MicroLC-ESI-Q-TOF-MS/MS, MALDI-TOF-MS, LC-MS/MS and nano-HPLC-ESI-MS/MS, respectively. Anti-allergic peptides from Atlantic salmon and Spirulina maxima [ 46 ] were identified by mass spectrometry techniques.…”

Novel angiotensin‐converting enzyme ( ACE ) inhibitory mechanism of peptides from Macadamia integrifolia antimicrobial protein 2 ( MiAMP2 )

“…MODELLER 9.24 was used to add the missing loop structure and atoms according to the complete AA sequence of ACE (Figure 1a) (Fiser & Do, 2000). The 3D structures of the unknown peptides for computational simulation were created in reference to our previous method (Zhao et al, 2021). AutoDock Vina package was used for docking simulation.…”

“…Macadamia nuts are very famous snack foods in different countries and contain significant amount of protein (∼8%), and fat (∼75%). Notably, they also contain a novel antimicrobial protein ( Macadamia integrifolia antimicrobial protein [MiAMP2]) being a part of 7S globulin which has many positive activities (Rost et al, 2020; Zhao et al, 2021).…”