title: Development of classification model and QSAR model for predicting binding affinity of endocrine disrupting chemicals to human sex hormone-binding globulin.
abstract: Disturbing the transport process is a crucial pathway for endocrine disrupting chemicals (EDCs) to disrupt endocrine function. However, this mechanism has not gotten enough attention, compared with that of hormone receptors and synthetase up to now, especially for the sex hormone transport process. In this study, we selected sex hormone-binding globulin (SHBG) and EDCs as a model system and the relative competing potency of a chemical with testosterone binding to SHBG (log RBA) as the endpoints, to develop classification models and quantitative structure-activity relationship (QSAR) models. With the classification model, a satisfactory model with nR09, nR10 and RDF155v as the most relevant variables was screened. Statistic results indicated that the model had the sensitivity, specificity, accuracy of 86.4%, 80.0%, 84.4% and 85.7%, 87.5%, 86.2% for the training set and validation set, respectively, highlighting a high classification performance of the model. With the QSAR model, a satisfactory model with statistical parameters, specifically, an adjusted determination coefficient (Radj(2)) of 0.810, a root mean square error (RMSE) of 0.616, a leave-one-out cross-validation squared correlation coefficient (QLOO(2)) of 0.777, a bootstrap method (QBOOT(2)) of 0.756, an external validation coefficient (Qext(2)) of 0.544 and a RMSEext of 0.859, were obtained, which implied satisfactory goodness of fit, robustness and predictive ability. The applicability domain of the current model covers a large number of structurally diverse chemicals, especially a few classes of nonsteroidal compounds.
authors.affiliation: Jiangsu Key Laboratory of Chemical Pollution Control and Resources Reuse, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, Jiangsu Province, China. Electronic address: hhliu@njust.edu.cn.
authors.forename: Huihui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Nanjing Institute of Environmental Sciences, Ministry of Environmental Protection, Jiang-wang-miao Street, Nanjing, 210042, China.
authors.forename: Xianhai
authors.initials: X
authors.lastname: Yang
authors.affiliation: Jiangsu Key Laboratory of Chemical Pollution Control and Resources Reuse, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, Jiangsu Province, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Lu
mesh_terms: D052244:Endocrine Disruptors / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D008962:Models, Theoretical; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*
chemical_list: D052244:Endocrine Disruptors; D012738:Sex Hormone-Binding Globulin
keywords: Classification model; Quantitative structure-activity relationship (QSAR); Relative binding affinity (RBA); Sex hormone-binding globulin (SHBG)