Molecular docking and molecular dynamics simulation studies of the interaction of anti-oral cancer plant Curcuma longa derived-compounds with human epidermal growth factor receptor 2

Oral cancer encompasses a heterogeneous group of malignant tumors affecting various regions of the oral cavity. This study aims to demonstrate the efficacy of phytotherapy in treating oral cancer, supported by molecular modeling evidence through the identification of bioactive molecules targeting the 3POZ receptor.

Molecular docking was used to assess the binding affinity of selected ligands within the active site of 3POZ. The best-docked ligand underwent molecular dynamics simulation of the associated complex for 100 ns using the Schrodinger suite of code. The pharmacokinetic properties and drug-like characteristics of selected compounds were evaluated by predicting ADMET parameters using SwissADME and pkCSM descriptors.

Out of 84 Curcuma longa compounds, 58 met Lipinski criteria, and 11 formed thermodynamically stable complexes with the 3POZ receptor. Among these, eight complexes were stabilized by hydrogen bonds, with compound C5 (3-Hydroxy-1,7-bis-(4-hydroxyphenyl)-6-heptene-1,5-dione) showing the best stabilization with three hydrogen bonds (Met 766, Met 793, Asp 855). None of the eight compounds exhibited hepatotoxic, genotoxic, or neurotoxic properties. Molecular dynamics simulations confirmed the stability of the best-docked protein–ligand complex, as evidenced by root-mean-square deviations, root-mean-square fluctuations, protein secondary structure elements, ligand-RMSF, protein–ligand contacts, ligand torsions, and ligand properties.

The use of artificial intelligence in biopharmaceutical research has validated the anticancer properties of Curcuma longa L. It is recommended that this plant be formulated into an appropriate galenic form (standardized phytomedicine) for clinical trials in managing oral cancer.