From In Silico De Novo Generation to In Vitro Functional Validation: Discovery of Multifunctional Antithrombotic Peptides from Food-Derived Proteins via a Hybrid LSTM-GCN and Molecular Simulation Pipeline
Abstract
Cardiovascular thromboses bring heavy global health burdens, while traditional screening of food-derived antithrombotic peptides is inefficient. This work built an integrated pipeline integrating de novo peptide generation, hybrid LSTM-GCN deep learning, and molecular simulations, screening 15,000 sequences to obtain lead peptide FPGGIP. It had a binding affinity of -6.4 kcal/mol and a stable thrombin complex (RMSD = 1.42 Å), acting as a competitive thrombin inhibitor (IC50 = 14.3 μM). FPGGIP exerted ex vivo anticoagulation, suppressed vascular smooth muscle proliferation, relieved oxidative stress, recovered cell apoptosis, alleviated endothelial activation, blocked platelet aggregation, and showed low hemolysis (
Fields of Study & Subjects
Biochemical and Structural Characterization
Chemical Synthesis and Analysis
Protein Hydrolysis and Bioactive Peptides
Publication details
- Journal / source
- Journal of Agricultural and Food Chemistry
- Publisher
- American Chemical Society (ACS)
- Volume
- 74
- Issue
- 32
- Pages
- 25347–25368
- Publication date
- 7 August 2026
- Language
- EN