Docking based virtual screening and molecular dynamics study to identify potential human epidermal receptor 2 inhibitors

Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor family possessing tyrosine kinase activity. Over expression of HER2 usually causes malignant transformation of cells and is responsible for about 25 to 30% of all breast cancer cases. With the aim to identify new chemical entities to be used for further rational drug design, a set of 762 molecules from the Zinc Database have been screened by docking experiments. The best ranked compounds with respect of the crystallographic inhibitor Pyr resulted to be three compounds, and the best among them was further tested by molecular dynamics simulation. Our results indicate that compound ZINC01398025 has a stronger interaction with the active site of HER2 TyK than Pyr and that both are able to stabilize specific conformational changes of the HER2 TyK 3D structure, which may explain their activity as inhibitors.