title: A new model of flavonoids affinity towards P-glycoprotein: genetic algorithm-support vector machine with features selected by a modified particle swarm optimization algorithm.
abstract: Flavonoids exhibit a high affinity for the purified cytosolic NBD (C-terminal nucleotide-binding domain) of P-glycoprotein (P-gp). To explore the affinity of flavonoids for P-gp, quantitative structure-activity relationship (QSAR) models were developed using support vector machines (SVMs). A novel method coupling a modified particle swarm optimization algorithm with random mutation strategy and a genetic algorithm coupled with SVM was proposed to simultaneously optimize the kernel parameters of SVM and determine the subset of optimized features for the first time. Using DRAGON descriptors to represent compounds for QSAR, three subsets (training, prediction and external validation set) derived from the dataset were employed to investigate QSAR. With excluding of the outlier, the correlation coefficient (R2) of the whole training set (training and prediction) was 0.924, and the R2of the external validation set was 0.941. The root-mean-square error (RMSE) of the whole training set was 0.0588; the RMSE of the cross-validation of the external validation set was 0.0443. The mean Q2value of leave-many-out cross-validation was 0.824. With more informations from results of randomization analysis and applicability domain, the proposed model is of good predictive ability, stability.
authors.affiliation: Department of Medicine Chemistry, Logistics College of Chinese People's Armed Police Forces, Tianjin, 300309, China.|Tianjin Key Laboratory of Occupational and Environmental Hazards Biomarkers, Tianjin, 300309, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Tianjin Anding Hospital, Tianjin, 300222, China.
authors.forename: Qinggang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Medicine Chemistry, Logistics College of Chinese People's Armed Police Forces, Tianjin, 300309, China.|Tianjin Key Laboratory of Occupational and Environmental Hazards Biomarkers, Tianjin, 300309, China.
authors.forename: Yaxiao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, 410008, China. xiaomafeng2000@gmail.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Tang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry* / Q000235:genetics; D066264:Datasets as Topic; D005419:Flavonoids / Q000737:chemistry*; D008956:Models, Chemical; D011485:Protein Binding; D000072417:Protein Domains; D021281:Quantitative Structure-Activity Relationship; D060388:Support Vector Machine
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005419:Flavonoids
keywords: Flavonoids; Genetic algorithm-support vector machine; Modified particle swarm optimization; P-glycoprotein affinity; Quantitative structure–activity relationships