HER2 over-expression associates with many cancer symptoms, and the HER2 protein kinase was regarded as the target for cancer treatment. To develop the novel potent leads,homology modeling and structure-based design were employed to this research. Three clinical trail drugs and traditional Chinese medicine (TCM) database were employed to perform the docking. The top 7 compounds from database with higher DockScore were selected to develop 210 virtual compounds by De novo evolution, and the 210 derivative compounds were further conform the Lipinskis Rule (rule of five) to ensure the rational in real condition. In the docking result of serial selection, CLC015-5, CLC015-11, CLC015-12, CLC604-11, and CLC604-18 presented the pi-stacking interaction and hydrogen bond interaction with the key residues, and had higher DockScore than clinical trail drugs and original compounds. These five selected compounds were suggested the potent ATP-binding inhibitors and might guide for further drug design.
IEEE/ACM Transactions on Computational Biology and Bioinformatics