Molecular Docking Based on Virtual Screening, Molecular Dynamics and Atoms in Molecules Studies to Identify the Potential Human Epidermal Receptor 2 Intracellular Domain Inhibitors

Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor family having tyrosine kinase activity. Overexpression of HER2 usually causes malignant transformation of cells and is responsible for the breast cancer. In this work, the virtual screening, molecular docking, quantum mechanics and molecular dynamics methods were employed to study protein–ligand interactions to be applied for drug design. The virtual screening was performed by docking among 762 chemicals derived from ZINC library to find specific inhibitors for active sites in HER2 intracellular. Among the best-ranked compounds in comparison with the crystallographic inhibitor pyrrolo [3, 2-d] pyrimidine, five compounds resulted and compound 1was further tested by molecular dynamics simulation and also quantum theory of atoms in molecules. The obtained results indicated that the interactions of compound 1 with the active site of HER2 TK are stronger than those of pyrrolo [3, 2-d] pyrimidine. Root mean square deviation, root mean square fluctuation, radius of gyration and binding free energy were calculated to check and evaluate the stability and mobility of the simulated system