Anxiety Disorder is prevalent worldwide and significantly impairs patients’ quality of life.γ-aminobutyric acid transaminase (GABA-T) is the rate-limiting enzyme for degrading the inhibitory neurotransmitter γ-aminobutyric acid (GABA), and inhibiting its activity can effectively relieve anxiety.This study aims to screen GABA-T inhibitory peptides with anti-anxiety potential from Spirulina phycocyanin by using computer simulation techniques.A multi-level screening strategy was constructed in this study.Firstly, virtual enzymatic digestion was performed on the phycocyanin amino acid sequence, and highly bioactive peptides were screened out through the PeptideRanker model.Then, polypeptides with high molecular docking binding energy were selected for toxicity, allergenicity, and water solubility predictions, followed by pharmacokinetic analysis.Finally, the mode of action of candidate peptides was revealed through molecular docking and molecular dynamics simulation.The results show that 49 highly bioactive peptides were obtained by enzymatic digestion.After molecular docking, 30 polypeptides with high docking binding energy were selected for physicochemical properties and pharmacokinetic analysis.Finally, three non-toxic, non-allergenic, water-soluble, and drug-like polypeptide sequences (CLNGLR, GRF, and QGRF) were obtained.The docking and dynamics simulation results revealed that these three polypeptides could bind to the key residues of GABA-T and maintain stable conformations during the dynamics simulation.This study indicates that Spirulina-derived polypeptides exhibit anti-anxiety activity by inhibiting GABA degradation, holding potential for development as natural anti-anxiety agents.
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