In Silico Molecular Docking Analysis of Diclofenac as an Inhibitor of Succinate Dehydrogenase (SDH)

Succinate Dehydrogenase (SDH) plays a crucial role in cellular energy metabolism and redox signaling, making it a significant target for metabolic studies. This study aimed to investigate the inhibitory potential of Diclofenac on SDH using in silico molecular docking analysis. The crystal structure of human SDH (PDB ID: 6VAX) was retrieved and prepared by removing water molecules, adding hydrogen atoms, and assigning Kollman and Gasteiger charges using AutoDock. Diclofenac's 3D structure was retrieved from PubChem, optimized using OpenBabel, and prepared for docking by adjusting torsion angles and charges. Blind docking simulations were conducted to explore potential binding sites across the SDH structure using AutoDock with default parameters. The results revealed significant binding affinity between Diclofenac and SDH, with a binding energy of -8.18 kcal/mol. A hydrogen bond was observed with LYS498, while hydrophobic interactions with key residues, including ASN495, GLN569, and TYR543, contributed to the stability and specificity of the Diclofenac-SDH complex. These interactions demonstrated Diclofenac’s potential to inhibit SDH function by stabilizing within the enzyme’s active site. This study confirms Diclofenac’s inhibitory activity on SDH through molecular docking, aligning with prior in vivo evidence of its metabolic impact. The findings provide valuable insights into the molecular mechanism of SDH inhibition and its potential implications for metabolic disorders.