XRCC4-DNA ligase IV complex is critical in non-homologous end-joining DNA repair system. Inhibition of its formation is potential in cancer cell killing, while no related study was reported. Herein, the structure-based drug design was used to develop potent compounds in this study. Firstly, the Traditional Chinese Medicine database was employed to dock into the binding site of XRCC4; then the top 10 output compounds were regarded as the scaffolds for further de novo evolution. Secondly, 99 diversities outcome were screened by Lipinski's Rule (rules of five) and the survivors were put into the second round of docking study. As a result, diversities with higher DockScore than the top 10 of DockScore from the first round were selected for pose analysis. Finally, 8 diversities were suggested to behave strongest inhibitory effects on XRCC4-DNA ligase IV complex formation. The 8 candidates selected by this study may serve as potent personalized anticancer drugs.
IEEE/ACM Transactions on Computational Biology and Bioinformatics