title: Novel design strategy for checkpoint kinase 2 inhibitors using pharmacophore modeling, combinatorial fusion, and virtual screening.
abstract: Checkpoint kinase 2 (Chk2) has a great effect on DNA-damage and plays an important role in response to DNA double-strand breaks and related lesions. In this study, we will concentrate on Chk2 and the purpose is to find the potential inhibitors by the pharmacophore hypotheses (PhModels), combinatorial fusion, and virtual screening techniques. Applying combinatorial fusion into PhModels and virtual screening techniques is a novel design strategy for drug design. We used combinatorial fusion to analyze the prediction results and then obtained the best correlation coefficient of the testing set (r test) with the value 0.816 by combining the Best(train)Best(test) and Fast(train)Fast(test) prediction results. The potential inhibitors were selected from NCI database by screening according to Best(train)Best(test) + Fast(train)Fast(test) prediction results and molecular docking with CDOCKER docking program. Finally, the selected compounds have high interaction energy between a ligand and a receptor. Through these approaches, 23 potential inhibitors for Chk2 are retrieved for further study.
authors.affiliation: Department of Computer Science and Information Engineering, Chang Gung University, Taoyuan 33302, Taiwan ; Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan 33302, Taiwan.
authors.forename: Chun-Yuan
authors.identifier: 0000-0003-1796-6189
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Department of Computer Science and Information Engineering, Chang Gung University, Taoyuan 33302, Taiwan.
authors.forename: Yen-Ling
authors.initials: YL
authors.lastname: Wang
mesh_terms: D064447:Checkpoint Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D014584:User-Computer Interface
chemical_list: D047428:Protein Kinase Inhibitors; D064447:Checkpoint Kinase 2