title: 2D-SAR and 3D-QSAR analyses for acetylcholinesterase inhibitors.
abstract: Alzheimer's disease (AD) accounts for almost three quarters of dementia patients and interferes people's normal life. Great progress has been made recently in the study of Acetylcholinesterase (AChE), known as one of AD's biomarkers. In this study, acetylcholinesterase inhibitors (AChEI) were collected to build a two-dimensional structure-activity relationship (2D-SAR) model and three-dimensional quantitative structure-activity relationship (3D-QSAR) model based on feature selection method combined with random forest. After calculation, the prediction accuracy of the 2D-SAR model was 89.63% by using the tenfold cross-validation test and 87.27% for the independent test set. Three cutting ways were employed to build 3D-QSAR models. A model with the highest [Formula: see text] (cross-validated correlation coefficient) and [Formula: see text](non-cross-validated correlation coefficient) was obtained to predict AChEI activity. The mean absolute error (MAE) of the training set and the test set was 0.0689 and 0.5273, respectively. In addition, molecular docking was also employed to reveal that the ionization state of the compounds had an impact upon their interaction with AChE. Molecular docking results indicate that Ser124 might be one of the active site residues.
authors.affiliation: Shanghai Key Laboratory of Bio-Energy Crops, College of Life Science, Shanghai University, Shanghai, 200444, People's Republic of China. Bingniu@shu.edu.cn.
authors.forename: Bing
authors.initials: B
authors.lastname: Niu
authors.affiliation: Shanghai Key Laboratory of Bio-Energy Crops, College of Life Science, Shanghai University, Shanghai, 200444, People's Republic of China.
authors.forename: Manman
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Shanghai Key Laboratory of Bio-Energy Crops, College of Life Science, Shanghai University, Shanghai, 200444, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Su
authors.affiliation: Shanghai Key Laboratory of Bio-Energy Crops, College of Life Science, Shanghai University, Shanghai, 200444, People's Republic of China.
authors.forename: Mengying
authors.initials: M
authors.lastname: Zhang
authors.affiliation: School of Materials Science and Engineering, Shanghai University, 99 Shangda Road, Shanghai, 200444, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lv
authors.affiliation: Shanghai Key Laboratory of Bio-Energy Crops, College of Life Science, Shanghai University, Shanghai, 200444, People's Republic of China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Shanghai Key Laboratory of Bio-Energy Crops, College of Life Science, Shanghai University, Shanghai, 200444, People's Republic of China.
authors.forename: Fuxue
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Life Science, Heze University, Heze, Shandong, 274500, People's Republic of China.
authors.forename: Dechang
authors.initials: D
authors.lastname: Chu
authors.affiliation: Shanghai Key Laboratory of Bio-Energy Crops, College of Life Science, Shanghai University, Shanghai, 200444, People's Republic of China. sdhzdds@163.com.|Department of Life Science, Heze University, Heze, Shandong, 274500, People's Republic of China. sdhzdds@163.com.
authors.forename: Dongshu
authors.initials: D
authors.lastname: Du
authors.affiliation: Changhai Hospital, Second Military Medical University, Shanghai, 200433, People's Republic of China. gong_chang2008@126.com.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D021281:Quantitative Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase
keywords: 2D-SAR; 3D-QSAR; AChE; Acetylcholinesterase inhibitors; Alzheimer’s disease; Molecular docking