title: Computer modeling in predicting the bioactivity of human 5-lipoxygenase inhibitors.
abstract: 5-Lipoxygenase (5-LOX) is a key enzyme in the inflammatory path. Inhibitors of 5-LOX are useful for the treatment of diseases like arthritis, cancer, and asthma. We have collected a dataset including 220 human 5-LOX inhibitors for classification. A self-organizing map (SOM), a support vector machine (SVM), and a multilayer perceptron (MLP) algorithm were used to build models with selected descriptors for classifying 5-LOX inhibitors into active and weakly active ones. MACCS fingerprints were used in this model building process. The accuracy (Q) and Matthews correlation coefficient (MCC) of the best SOM model (Model 1A) were 86.49% and 0.73 on the test set, respectively. The Q and MCC of the best SVM model (Model 2A) were 82.67% and 0.64 on the test set, respectively. The Q and MCC of the best MLP model (Model 3B) were 84.00% and 0.67 on the test set, respectively. In addition, 180 inhibitors with bioactivities measured by fluorescence method were further used for a quantitative prediction. Multiple linear regression (MLR) and SVM algorithms were used to build models to predict the [Formula: see text] values. The correlation coefficients (R) of the MLR model (Model Q1) and the SVM model (Model Q2) were 0.72 and 0.74 on the test set, respectively.
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Department of Pharmaceutical Engineering, Beijing University of Chemical Technology, P.O. Box 53, 15 BeiSanHuan East Road, Beijing, 100029, People's Republic of China.
authors.forename: Mengdi
authors.initials: M
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Department of Pharmaceutical Engineering, Beijing University of Chemical Technology, P.O. Box 53, 15 BeiSanHuan East Road, Beijing, 100029, People's Republic of China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Department of Pharmaceutical Engineering, Beijing University of Chemical Technology, P.O. Box 53, 15 BeiSanHuan East Road, Beijing, 100029, People's Republic of China. yanax@mail.buct.edu.cn.|State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, People's Republic of China. yanax@mail.buct.edu.cn.
authors.forename: Aixia
authors.initials: A
authors.lastname: Yan
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D003198:Computer Simulation; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D060388:Support Vector Machine
chemical_list: D016859:Lipoxygenase Inhibitors; D001094:Arachidonate 5-Lipoxygenase
keywords: Human 5-lipoxygenase (5-LOX) inhibitors; Multilayer perceptron network (MLP); Self-organizing map (SOM); Structure–activity relationship (SAR); Support vector machine (SVM)