Pharmacophore modeling, virtual screening, molecular docking and dynamics studies for the discovery of HER2-tyrosine kinase inhibitors: An in-silico approach

Abstract

Breast cancer is the most common causes of death noticed in women globally. In order to find an effective therapeutic agents our current investigation concentrating on an identification of potent candidate compounds for HER2 inhibition. Initially we performed a ligand-based pharmacophore modeling approaches for an identification of prospective compounds. Focusing on the HER2 results the final three hits have a good binding affinity towards the target. These three hits showed an established a key residue interactions with the stable molecular dynamics simulation results. Our in-silico studies revealed that the, final hits had a molecular interactions within the ATP binding site of the targeted protein such as HER2. The stability of the ligand-protein complex is stable throughout the simulation run. From the results obtained from the in-silico studies, we proposed that these final hits are exceptionally useful for further lead optimization and drug development process.