3D-QSAR Study for Checkpoint Kinase 2 Inhibitors through Pharmacophore Hypotheses

DNA-damage is induced by ionizing radiation, genotoxic chemicals or collapsed replication forks. To prevent and repair the DNA-damage, mammalian cells will control and stabilize the genome by cell cycle checkpoint. Checkpoint kinase 2 (Chk2) is one of the important kinases that has a great effect on DNA-damage and plays an important role in response to DNA double-strand breaks and related lesions. Hence, in this study, we will concentrate on Chk2 and the purpose is to build the pharmacophore hypotheses (PhModels) by 3D-QSAR study which can identify inhibitors with high biological activities. Ten PhModels were generated by the HypoGen Best algorithm. The established PhModel, Hypo01, was evaluated in the cost function analysis of its correlation coefficient (r), RMS, cost difference, and configuration cost, with the values: 0.955, 1.28, 192.51, and 16.07, respectively. The result of Fischer’s cross-validation test for Hypo01 model yielded a 95% confidence level, and the correlation coefficient (rtest) of the testing set yielded a best value of 0.81.