In Silico Molecular Docking and Binding Affinity Analysis Between Luteolin and the Human Serotonin Transporter (Sert) for Generalised Anxiety Disorder

Generalized Anxiety Disorder (GAD) is a prevalent psychiatric condition worldwide and is closely associated with dysregulation of key neurotransmitters, particularly serotonin. The serotonin transporter (SERT) is a crucial membrane protein responsible for the reuptake of serotonin from the synaptic cleft and its inhibition represents an established therapeutic strategy for restoring neurochemical balance and alleviating anxiety symptoms. In the present in silico investigation, the molecular interaction profile and therapeutic potential of luteolin (compound ID: 5280445), a naturally occurring flavonoid, were evaluated against the human SERT protein (PDB ID: 5I6X). Molecular docking simulations were performed using BIOVIA Discovery Studio Visualizer, with energy minimization employed to ensure structural stability of the ligand–protein complex. The docking analysis demonstrated that luteolin exhibits strong binding affinity and favourable structural complementarity within the active site of SERT. The stability of the complex was primarily mediated by robust hydrogen bond interactions with key amino acid residues Asp98A and Ala96A, along with significant hydrophobic interactions involving Tyr176A, Ile172A and Ser438A. These findings suggest that luteolin possesses promising inhibitory activity against SERT and may serve as a potential natural lead compound for the development of safer and effective anxiolytic agents.