title: In silico investigation of traditional Chinese medicine compounds to inhibit human histone deacetylase 2 for patients with Alzheimer's disease.
abstract: Human histone deacetylase 2 (HDAC2) has been identified as being associated with Alzheimer's disease (AD), a neuropathic degenerative disease. In this study, we screen the world's largest Traditional Chinese Medicine (TCM) database for natural compounds that may be useful as lead compounds in the search for inhibitors of HDAC2 function. The technique of molecular docking was employed to select the ten top TCM candidates. We used three prediction models, multiple linear regression (MLR), support vector machine (SVM), and the Bayes network toolbox (BNT), to predict the bioactivity of the TCM candidates. Molecular dynamics simulation provides the protein-ligand interactions of compounds. The bioactivity predictions of pIC50 values suggest that the TCM candidatesm, (-)-Bontl ferulate, monomethylcurcumin, and ningposides C, have a greater effect on HDAC2 inhibition. The structure variation caused by the hydrogen bonds and hydrophobic interactions between protein-ligand interactions indicates that these compounds have an inhibitory effect on the protein.
authors.affiliation: Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan.
authors.forename: Tzu-Chieh
authors.initials: TC
authors.lastname: Hung
authors.affiliation: Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan ; School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan ; Department of Neurosurgery, China Medical University Hospital, No. 2, Yude Road, North District, Taichung 40447, Taiwan.
authors.forename: Wen-Yuan
authors.initials: WY
authors.lastname: Lee
authors.affiliation: Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan ; School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan ; Department of Anesthesiology, China Medical University Hospital, Taichung 40447, Taiwan.
authors.forename: Kuen-Bao
authors.initials: KB
authors.lastname: Chen
authors.affiliation: School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan.
authors.forename: Yueh-Chiu
authors.initials: YC
authors.lastname: Chan
authors.affiliation: School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan.
authors.forename: Cheng-Chun
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan ; School of Medicine, College 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: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D056464:Histone Deacetylase 2 / Q000037:antagonists & inhibitors*; D006801:Humans; D008024:Ligands; D008516:Medicine, Chinese Traditional; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D021281:Quantitative Structure-Activity Relationship; D060388:Support Vector Machine
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; C533423:HDAC2 protein, human; D056464:Histone Deacetylase 2