<p>The 18-kDa translocator protein (TSPO) is a key target of research aimed at understanding the mechanisms of neuroinflammation and stress-associated disorders. TSPO ligands exhibit significant therapeutic potential, including anxiolytic, antidepressant, and neuroprotective effects, making them promising for new drug development. However, the mechanisms of TSPO interaction with various ligands require more detailed studies using modern molecular dynamics methods, which were used in the present work to study the molecular interactions of the TSPO protein (PDB ID: 2MGY) with its promising ligands GML-1 and GML-3, including a comparative analysis with known TSPO ligands PK-11195, Ro5-4864, and etifoxine. The study was conducted using the Schrodinger software package (version 2024-2). The analysis included evaluations of the RMSD, RMSF, binding free energy (∆G), hydrophobic interactions, hydrogen bonds, and other types of molecular contacts. The ligands GML-1 and GML-3 demonstrated high structural stability in complexes with TSPO protein (RMSD: 1 – 3 Å) and favorable binding free energies (∆G ≈ –69.74 and –67.68 kcal/mol, respectively), comparable to those for PK-11195 and etifoxine. Interaction analysis showed that GML-1 and GML-3 formed stable hydrophobic contacts and hydrogen bonds with key amino acid residues of TSPO protein such as TRP_107, LEU_49, and VAL_26, which played important roles in stabilizing the complex. Compared to known ligands, GML-1 and GML-3 provided similar structural stability and binding energy, while demonstrating high stability of the complex in molecular dynamics. These properties make them promising targets for further research and development of drugs that modulate TSPO activity.</p>