Molecular Docking-based Virtual Screening, Molecular Dynamics and Atoms in Molecules (AIM) Studies to Identify Potential Inhibitor against the Extracellular Region of Human Epidermal Receptor 2

In this study, molecular docking, quantum mechanics and molecular dynamics methods were used to investigate protein-ligand interactions of the epidermal growth factor receptor 2 (HER2 ). The virtual screening was performed by docking among 2000 chemicals derived from the ZINC library to find specific inhibitors. Trastuzumab is the active site in the HER2 extracellular domain and the target area. The scoring function was used to calculate the binding affinity of the found inhibitors to the active site of the HER2. Among the found inhibitors, six ligands were chosen based on suitable electronic structure and energy. The H-bond interaction energies between six ligands and HER2 were investigated and bond critical points were determined for each bond path between the two corresponding atoms by the quantum theory of atoms in molecules. Root mean square deviation, root mean square fluctuation, the radius of gyration and binding free energy were calculated to check and evaluate the stability and mobility of the simulated system using molecular dynamics simulation.