Computer-Aided Screening and Revealing Action Mechanism of Food-Derived Tripeptides Intervention in Acute Colitis

Area of Science:

• Nutritional biochemistry
• Computational biology
• Pharmacology

Background:

• Colitis symptoms can be alleviated by food-derived tripeptides.
• The precise mechanisms of tripeptide action in colitis are not well understood.
• There is a need for novel nutritional compounds for colitis management.

Purpose of the Study:

• To investigate the therapeutic mechanisms of food-derived tripeptides against acute colitis.
• To identify potential molecular targets and signaling pathways involved in tripeptide-mediated colitis relief.
• To screen a large library of tripeptides for their efficacy against colitis using computational approaches.

Main Methods:

• Utilized a computer-aided screening strategy to evaluate 8000 food-derived tripeptides.
• Constructed protein-protein and protein-tripeptide networks using PharmMapper and STRING.
• Identified key signaling pathways (e.g., Ras, PI3K-Akt) via DAVID software.
• Performed molecular docking of selected tripeptides against major targets (AKT1, EGFR, MMP9) using Autodock.

Main Results:

• Identified 41 hub targets and 30 significant KEGG pathways related to inflammation and cell regulation in colitis.
• Discovered 52 tripeptides with significant binding affinities to target proteins AKT1, EGFR, and MMP9.
• Molecular docking revealed hydrogen-bonding and hydrophobic interactions with binding energies mostly below -7.13 kcal/mol.

Conclusions:

• Food-derived tripeptides exhibit potential therapeutic mechanisms for colitis.
• Computational screening effectively identified promising tripeptide candidates and their molecular targets.
• This study provides a foundation for developing tripeptide-based nutritional therapies for colitis.