Discovery of bifunctional anti-DPP-IV and anti-ACE peptides from housefly larval proteins after in silico gastrointestinal digestion

Abstract

Proteins and peptides of housefly larvae (HFL) have potential applications in food and therapy. The fate of HFL proteins following human gastrointestinal (GI) digestion is unknown. This study adopted a computational approach to discover peptides released from HFL proteins upon GI digestion. In silico digestion of eight major HFL proteins released 783 peptides. This comprised 243 peptides exhibiting 13 types of bioactivities. Ninety-two single-function peptides exhibiting anti- dipeptidyl peptidase IV (anti-DPP-IV), anti-dipeptidyl peptidase III, anti-angiotensin converting enzyme (anti-ACE), or antioxidant activity were found. Sixty-three multi-function peptides, encompassing 32 bifunctional anti-DPP-IV and anti-ACE peptides, were found. Further screening led to five non-toxic, non-allergenic, high-GI-absorption bifunctional dipeptides: AF, GW, GY, PH, and VF. Molecular docking found the dipeptides to interact with the active site of DPP-IV through hydrophobic interactions. Only GW and VF could bind to the active site of ACE. Thus, the five dipeptides are competitive inhibitors of DPP-IV. GW and VF are potential competitive inhibitors of ACE, whereas AF, GY, and PH are non-competitive inhibitors. Overall, GI digestion could liberate numerous single- and multi-function peptides from HFL proteins. Hence, HFL proteins can be tapped for potential applications in antidiabetic and antihypertension functional food and therapy.