In Silico Molecular Docking of Niazimicin A with DPP-4 Using AutoDock Vina and Interaction Profiling

Objective: Type 2 diabetes mellitus (T2DM) is characterised by progressive β-cell dysfunction and chronic hyperglycaemia. The enzyme Dipeptidyl peptidase-4 (DPP-4) is an important therapeutic target which is involved in the degradation of incretin hormones such as Glucagon-like peptide-1 (GIP) and Glucose-dependent insulin tropic polypeptide (GIP). Despite several DPP-4 inhibitors in use, there are rising concerns regarding their cost, adverse effects and long-term safety. Niazimicin A, a type of thiocarbamate glycoside isolated from Moringaoleifera Lam., has demonstrated pharmacological activities; but its interaction with DPP-4 remains unexplored. This molecular docking study investigated the binding potential of Niazimicin A against DPP-4. Methods: Protein data bank was used to retrieve the three-dimensional structure of DPP-4 (PDB ID: 5Y7H) and was prepared for docking. Niazimicin A (PubChem C ID: 10247749) was optimised and converted into PDBQT format. AutoDock Vina was used for molecular docking with a predefined grid box. Protein–ligand interactions were analysed using discovery studio visualizer and docking validation was performed through re-docking of the co-crystallized ligand. Results: Niazimicin A showed stable docking poses ranging from − 2.816 to −0.090 kcal/mol with a best binding energy of −2.816 kcal/mol. The interaction analysis identified hydrogen bonds with GLN714, SER239, PHE713 and THR706 along with carbon-hydrogen and hydrophobic interactions involving TYR238, TYR241 and PRO249. Docking validation confirmed accurate reproduction of the native ligand binding pose. Conclusion: Niazimicin A exhibited favourable non-covalent interactions within the DPP-4 active site, suggesting its potential as a natural lead compound for antidiabetic drug discovery. Further experimental and pharmacokinetic studies are recommended.