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

Lei Zhao; Mingxin Zhang; Fei Pan; Jiayi Li; Ran Dou; Xinyi Wang; Yangyang Wang; Yumeng He; Shaoxuan Wang; Shengbao Cai

doi:10.1016/j.crfs.2021.08.008

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

Curr Res Food Sci. 2021 Sep 2:4:603-611. doi: 10.1016/j.crfs.2021.08.008. eCollection 2021.

Authors

Lei Zhao¹, Mingxin Zhang¹, Fei Pan¹, Jiayi Li², Ran Dou¹, Xinyi Wang¹, Yangyang Wang¹, Yumeng He¹, Shaoxuan Wang¹, Shengbao Cai³

Affiliations

¹ Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University, Beijing, 100048, China.
² State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.
³ Faculty of Agriculture and Food, Yunnan Institute of Food Safety, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China.

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.

Keywords: Diabetes; Dipeptidyl peptidase IV inhibitors; Macadamia nut protein; Molecular docking; Molecular dynamic simulation; Network pharmacology.