Molecular Docking Analysis of Haloperidol Binding to the D2 Dopamine Receptor Using Auto Dock Vine and PyMOL

The dopamine D2 receptor (PDB ID: 6CM4) plays a crucial role in the pharmacological action of antipsychotic drugs, distinguishing between atypical and typical antipsychotic interactions. In this study, we investigated the binding interaction of Haloperidol (GMJ) with the D2 receptor using molecular docking via Auto Dock Vina. The receptor structure was processed by removing unnecessary chains, ligands, and water molecules while adding polar hydrogens and appropriate charges. Similarly, the ligand was optimized by assigning polar hydrogens and torsions. A docking grid was defined at coordinates (center_x = -0.274, center_y = -0.120, center_z = 0.082) with a box size of 60 × 60 × 60. Docking results revealed that Haloperidol exhibited a strong binding affinity with the D2 receptor, with the best binding mode showing energy of -11.1 kcal/mol. The top five docking poses consistently displayed high affinity, with affinities ranging from -11.1 to -10.0 kcal/mol. Structural alignment in PyMOL indicated a root mean square deviation (RMSD) of 0.905 Å after iterative rejection of misaligned atoms, suggesting a reliable binding pose. Notably, the docked ligand maintained a spatial alignment close to the original ligand, reinforcing the validity of the docking approach. These findings provide valuable insights into the molecular interactions of Haloperidol with the D2 receptor, highlighting its strong binding potential. This study contributes to a deeper understanding of antipsychotic drug-receptor interactions, which may aid in drug design and optimization efforts for neuropsychiatric treatments. Keywords: Dopamine D2 receptor, Haloperidol, Molecular docking, Auto Dock Vina, Drug-receptor interaction, Binding affinity, Antipsychotic drugs