title: Discrimination of Active and Weakly Active Human BACE1 Inhibitors Using Self-Organizing Map and Support Vector Machine.
abstract: β-secretase (BACE1) is an aspartyl protease, which is considered as a novel vital target in Alzheimer`s disease therapy. We collected a data set of 294 BACE1 inhibitors, and built six classification models to discriminate active and weakly active inhibitors using Kohonen's Self-Organizing Map (SOM) method and Support Vector Machine (SVM) method. Each molecular descriptor was calculated using the program ADRIANA.Code. We adopted two different methods: random method and Self-Organizing Map method, for training/test set split. The descriptors were selected by F-score and stepwise linear regression analysis. The best SVM model Model2C has a good prediction performance on test set with prediction accuracy, sensitivity (SE), specificity (SP) and Matthews correlation coefficient (MCC) of 89.02%, 90%, 88%, 0.78, respectively. Model 1A is the best SOM model, whose accuracy and MCC of the test set were 94.57% and 0.98, respectively. The lone pair electronegativity and polarizability related descriptors importantly contributed to bioactivity of BACE1 inhibitor. The Extended-Connectivity Finger-Prints_4 (ECFP_4) analysis found some vitally key substructural features, which could be helpful for further drug design research. The SOM and SVM models built in this study can be obtained from the authors by email or other contacts.
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.forename: Maolin
authors.initials: M
authors.lastname: Wang
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Gong
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Department of Pharmaceutical Engineering, P.O. Box 53, Beijing University of Chemical Technology, 15 BeiSanHuan East Road, Beijing 100029, P.R. China. yanax@mail.buct.edu.cn.
authors.forename: Aixia
authors.initials: A
authors.lastname: Yan
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D016014:Linear Models; D012680:Sensitivity and Specificity; D060388:Support Vector Machine
chemical_list: D004791:Enzyme Inhibitors; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human