Computational Screening and Molecular Docking Analysis of Bioactive Peptides from Spent Coffee Grounds as Potential α-Glucosidase and α-Amylase Inhibitors for Antidiabetic Therapy

A metabolic disease, type 2 diabetes mellitus (T2DM), is marked by chronic hyperglycemia due to insulin resistance or impaired secretion. Inhibiting carbohydrate-digesting enzymes, particularly α-glucosidase and α-amylase, is a therapeutic approach to regulate blood glucose levels. Protein components of spent coffee grounds (SCG), a byproduct of coffee production, can be hydrolyzed to produce bioactive peptides with potential health benefits. In this study, the 11S storage protein of SCG was simulated with alcalase digestion for peptide synthesis. These peptides were computationally screened for antidiabetic potential using bioactivity prediction tools and were evaluated for bioactivity, toxicity, bitterness, blood stability, and protein-binding potential. Most were predicted to be non-toxic, non-bitter, and had favorable blood half-lives (>830 s), suggesting therapeutic viability. Molecular docking was performed against α-glucosidase and α-amylase to assess binding affinity. The amino acids TRP406, ARG526, and ASP542 of α-glucosidase were strongly bound by the peptides GRPQPRL and RRF, which had binding strengths of -8.5 and -8.3 kcal/mol, respectively. Meanwhile, ASP197, GLU233, ASP300, HIS299, and HIS305 were key components of α-amylase’s binding with APHW (-8.7 kcal/mol). The presence of aromatic and polar residues contributed to binding strength and stability in enzyme active sites. These results indicate that SCG-derived peptides have promising inhibitory activity against α-glucosidase and α-amylase and may serve as natural, safe, and stable candidates for developing functional antidiabetic therapies.