title: Development and evaluation of predictive model for bovine serum albumin-water partition coefficients of neutral organic chemicals.
abstract: The binding of organic chemicals to serum albumin can significantly reduce their unbound concentration in blood and affect their biological reactions. In this study, we developed a new QSAR model for bovine serum albumin (BSA) - water partition coefficients (KBSA/W) of neutral organic chemicals with large structural variance, logKBSA/Wvalues covering 3.5 orders of magnitude (1.19-4.76). All chemical geometries were optimized by semi-empirical PM6 algorithm. Several quantum chemical parameters that reflect various intermolecular interactions as well as hydrophobicity were selected to develop QSAR model. The result indicates the regression model derived from logKow, the most positive net atomic charges on an atom, Connolly solvent excluded volume, polarizability, and Abraham acidity could explain the partitioning mechanism of organic chemicals between BSA and water. The simulated external validation and cross validation verifies the developed model has good statistical robustness and predictive ability, thus can be used to estimate the logKBSA/Wvalues for chemicals in application domain, accordingly to provide basic data for the toxicity assessment of the chemicals.
authors.affiliation: College of Geography and Environmental Sciences, Zhejiang Normal University, Yingbin Avenue 688, 321004, Jinhua, PR China.
authors.forename: Guangcai
authors.initials: G
authors.lastname: Ma
authors.affiliation: College of Geography and Environmental Sciences, Zhejiang Normal University, Yingbin Avenue 688, 321004, Jinhua, PR China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: College of Geography and Environmental Sciences, Zhejiang Normal University, Yingbin Avenue 688, 321004, Jinhua, PR China. Electronic address: yhy@zjnu.cn.
authors.forename: Haiying
authors.initials: H
authors.lastname: Yu
authors.affiliation: College of Geography and Environmental Sciences, Zhejiang Normal University, Yingbin Avenue 688, 321004, Jinhua, PR China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Lin
authors.affiliation: College of Geography and Environmental Sciences, Zhejiang Normal University, Yingbin Avenue 688, 321004, Jinhua, PR China.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Chen
authors.affiliation: College of Geography and Environmental Sciences, Zhejiang Normal University, Yingbin Avenue 688, 321004, Jinhua, PR China.
authors.forename: Huachang
authors.initials: H
authors.lastname: Hong
mesh_terms: D057927:Hydrophobic and Hydrophilic Interactions; D008956:Models, Chemical; D009930:Organic Chemicals / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D009930:Organic Chemicals; D014867:Water; D012710:Serum Albumin, Bovine
keywords: Bovine serum albumin – water partition coefficients; PM6; QSAR; Quantitative structure – property relationship; Quantum chemical descriptors