Current Journal of Applied Science and Technology

Aims: To evaluate the predicted interactions of six andaliman (Zanthoxylum acanthopodium DC.) phytochemicals, namely quercetin, 4-coumaric acid, isorhamnetin, berberine, ferulic acid, and kaempferol, with the HER2 kinase domain using a molecular docking protocol validated by re-docking.

Study Design: A computational in silico study using a structure-based molecular docking approach.

Place and Duration of Study: Computational analysis using molecular structures obtained from the RCSB Protein Data Bank and PubChem. No physical study site was involved.

Methodology: Chain A of the HER2 kinase structure (PDB ID 3PP0) was used as the receptor. The docking protocol was validated by re-docking the co-crystallised ligand 03Q using AutoDock Vina 1.1.2. The grid box was centred at 17.098971, 16.548676, and 26.600647 Å with a size of 20 × 20 × 20 ų and an exhaustiveness of 16. Heavy-atom RMSD was calculated using Open Babel obrms. The six phytochemicals, together with the reference ligands lapatinib and TAK-285, were then docked into the same binding site. Binding affinity and ligand–protein interactions were analysed using PyMOL.

Results: Re-docking of 03Q yielded a heavy-atom RMSD of 0.70355 Å, below the 2.0 Å threshold. The phytochemicals showed binding affinities ranging from −6.5 to −9.9 kcal/mol, compared with −10.6 and −12.1 kcal/mol for lapatinib and TAK-285, respectively. Berberine showed polar contacts with ASP863, MET801, and GLY804, while kaempferol formed one confirmed hydrogen bond with ASP863. Both reference ligands formed confirmed hydrogen bonds with SER728. No geometrically supported π–π interactions were identified.

Conclusion: The docking protocol satisfied the operational validation criterion. The findings provide initial structural insights into andaliman phytochemical interactions with HER2; however, the results remain predictive and require further computational and experimental validation.