title: SAR and QSAR study on the bioactivities of human epidermal growth factor receptor-2 (HER2) inhibitors.
abstract: In this paper, structure-activity relationship (SAR, classification) and quantitative structure-activity relationship (QSAR) models have been established to predict the bioactivity of human epidermal growth factor receptor-2 (HER2) inhibitors. For the SAR study, we established six SAR (or classification) models to distinguish highly and weakly active HER2 inhibitors. The dataset contained 868 HER2 inhibitors, which was split into a training set including 580 inhibitors and a test set including 288 inhibitors by a Kohonen's self-organizing map (SOM), or a random method. The SAR models were performed using support vector machine (SVM), random forest (RF) and multilayer perceptron (MLP) methods. Among the six models, SVM models obtained superior results compared with other models. The prediction accuracy of the best model (model 1A) was 90.27% and the Matthews correlation coefficient (MCC) was 0.80 on the test set. For the QSAR study, we chose 286 HER2 inhibitors to establish six quantitative prediction models using MLR, SVM and MLP methods. The correlation coefficient (r) of the best model (model 4B) was 0.92 on the test set. The descriptors analysis showed that HAccN, lone pair electronegativity and π electronegativity were closely related to the bioactivity of HER2 inhibitors.
authors.affiliation: a State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology , Beijing , P.R. China.
authors.forename: D
authors.initials: D
authors.lastname: Qu
authors.affiliation: a State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology , Beijing , P.R. China.
authors.forename: A
authors.initials: A
authors.lastname: Yan
authors.affiliation: b The High School Affiliated to Renmin University of China , Beijing , P.R. China.
authors.forename: J S
authors.initials: JS
authors.lastname: Zhang
mesh_terms: D006801:Humans; D015233:Models, Statistical; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D021281:Quantitative Structure-Activity Relationship; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D004364:Pharmaceutical Preparations; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Human epidermal growth factor receptor-2 (HER2) inhibitor; multiple linear regression (MLR); quantitative structure–activity relationship (QSAR); random forest (RF); structure–activity relationship (SAR); support vector machine (SVM)