title: A genetic algorithm- back propagation artificial neural network model to quantify the affinity of flavonoids toward P-glycoprotein.
abstract: Flavonoids, the most diverse class of plant secondary metabolites, exhibit high affinity toward the purified cytosolic NBD2(C-terminal nucleotide-binding domain) of P-glycoprotein (P-gp). To explore the affinity of flavonoids for P-gp, quantitative structure-activity relationships (QSARs) models were developed using back-propagation artificial neural networks (BPANN) and multiple linear regression (MLR). Molecular descriptors were calculated using PaDELDescriptor, and the number of descriptors was then reduced using a genetic algorithm (GA) and stepwise regression. The MLR (R(2)=0.855, q(2)=0.8138, Rext(2)=0.6916), 14-3-1 BPANN (R(2)=0.8514, q(2)=0.7695, Rext (2)=0.8142), 14-4-1 BPANN(R(2)=0.9199, q(2)=0.7733, Rext(2) =0.8731), and 14-5-1 BPANN (R(2)=0.8660, q(2)=0.7432, Rext(2)=0.8292) models all showed good robustness. While BPANN models exceeded significantly MLR in predictable performance for their flexible characters, could be used to predict the affinity of flavonoids for P-gp and applied in further drug screening.
authors.forename: Jibin
authors.initials: J
authors.lastname: Shen
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.forename: Yaxiao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Medicine Chemistry, Logistics College of Chinese People's Armed Police Forces, China. llzhx@tom.com.
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Li
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000465:Algorithms; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D016014:Linear Models; D008954:Models, Biological; D016571:Neural Networks, Computer; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005419:Flavonoids