title: Drug design of cyclin-dependent kinase 2 inhibitor for melanoma from traditional Chinese medicine.
abstract: One has found an important cell cycle controller. This guard can decide the cell cycle toward proliferation or quiescence. Cyclin-dependent kinase 2 (CDK2) is a unique target among the CDK family in melanoma therapy. We attempted to find out TCM compounds from TCM Database@Taiwan that have the ability to inhibit the activity of CDK2 by systems biology. We selected Tetrahydropalmatine, Reserpiline, and (+)-Corydaline as the candidates by docking and screening results for further survey. We utilized support vector machine (SVM), multiple linear regression (MLR) models and Bayesian network for validation of predicted activity. By overall analysis of docking results, predicted activity, and molecular dynamics (MD) simulation, we could conclude that Tetrahydropalmatine, Reserpiline, and (+)-Corydaline had better binding affinity than the control. All of them had the ability to inhibit the activity of CDK2 and might have the opportunity to be applied in melanoma therapy.
authors.affiliation: Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan.
authors.forename: Hsin-Chieh
authors.initials: HC
authors.lastname: Tang
authors.affiliation: Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan ; Department of Medicine, China Medical University, Taichung 40402, Taiwan ; Research Center for Chinese Medicine & Acupuncture, China Medical University, Taichung 40402, Taiwan ; Human Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung 40447, Taiwan.
authors.forename: Calvin Yu-Chian
authors.identifier: 0000-0003-3306-250X
authors.initials: CY
authors.lastname: Chen
mesh_terms: D001600:Berberine Alkaloids / Q000737:chemistry / Q000627:therapeutic use; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors / Q000737:chemistry*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D008516:Medicine, Chinese Traditional; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D056004:Molecular Dynamics Simulation; D021281:Quantitative Structure-Activity Relationship
chemical_list: D001600:Berberine Alkaloids; D004791:Enzyme Inhibitors; C452799:corydaline; C014215:tetrahydropalmatine; D051357:Cyclin-Dependent Kinase 2