1. Academic Validation
  2. Virtual Screening of GLP-1-Secreting Peptides from Pea Protein Hydrolysates via Peptide Transporter 1 (PepT1) Activation-Based Molecular Docking

Virtual Screening of GLP-1-Secreting Peptides from Pea Protein Hydrolysates via Peptide Transporter 1 (PepT1) Activation-Based Molecular Docking

  • J Agric Food Chem. 2024 Jun 7. doi: 10.1021/acs.jafc.4c00999.
Mingkai Zhang 1 Ling Zhu 1 Hui Zhang 1 Xingguo Wang 1 Tongtong Liu 1 Gangcheng Wu 1
Affiliations

Affiliation

  • 1 National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China.
Abstract

Dietary proteins regulate glucose homeostasis via intestinal protein sensing-induced glucagon-like peptide 1 (GLP-1) secretion. However, the reported GLP-1-secreting Peptides derived from dietary proteins are few, and studies regarding GLP-1-secreting peptide identification by traditional separation and purification methods are laborious. Herein, we have rapidly virtual-screened two GLP-1 secreting Peptides from pea protein hydrolysates (PPHs) by peptidomic analysis and molecular docking with peptide transporter 1 (PepT1). PPH-stimulated GLP-1 secretion decreased after adding the PepT1 antagonist 4-aminobenzoic acid (4-AMBA), indicating that PepT1 activation was involved in PPH-induced GLP-1 secretion in NCI-H716 cells. Subsequently, 307 Tripeptides in PPHs were obtained through peptidomic analysis. Among them, two GLP-1-secreting Peptides, FLR and LRW, were identified via PepT1 activation-based molecular docking. FLR and LRW (1 mg/mL) increased GLP-1 levels to 170.20% ± 27.83% and 272.37% ± 45.96%, respectively (p < 0.05). More importantly, molecular docking implied that the interactions between Peptides and the active center of PepT1 (especially Glu595, Asn329, and Asn171 in the N-pocket and Arg27 in the C-pocket) were crucial for peptide activity in stimulating GLP-1 secretion. Our study suggested that the combination of peptidomics and PepT1 activation-based molecular docking is a promising approach for identification of GLP-1-secreting Peptides.

Keywords

GLP-1; PepT1; molecular docking; pea peptides; virtual screening.

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