title: In silico Prediction of Aqueous Solubility: a Comparative Study of Local and Global Predictive Models.
abstract: 32 Quantitative Structure-Property Relationship (QSPR) models were constructed for prediction of aqueous intrinsic solubility of liquid and crystalline chemicals. Data sets contained 1022 liquid and 2615 crystalline compounds. Multiple Linear Regression (MLR), Support Vector Machine (SVM) and Random Forest (RF) methods were used to construct global models, and k-nearest neighbour (kNN), Arithmetic Mean Property (AMP) and Local Regression Property (LoReP) were used to construct local models. A set of the best QSPR models was obtained: for liquid chemicals with RMSE (root mean square error) of prediction in the range 0.50-0.60 log unit; for crystalline chemicals 0.80-0.90 log unit. In the case of global models the large number of descriptors makes mechanistic interpretation difficult. The local models use only one or two descriptors, so that a medicinal chemist working with sets of structurally-related chemicals can readily estimate their solubility. However, construction of stable local models requires the presence of closely related neighbours for each chemical considered. It is probable that a consensus of global and local QSPR models will be the optimal approach for construction of stable predictive QSPR models with mechanistic interpretation.
authors.affiliation: Department of Computer-Aided Molecular Design, Institute of Physiologically Active Compounds, Russian Academy of Science, 142432, Russia, Chernogolovka, Severniy proezd 1 phone: +7 496 52 21867. raevsky@ipac.ac.ru.
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Raevsky
authors.affiliation: Department of Computer-Aided Molecular Design, Institute of Physiologically Active Compounds, Russian Academy of Science, 142432, Russia, Chernogolovka, Severniy proezd 1 phone: +7 496 52 21867.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Polianczyk
authors.affiliation: Department of Computer-Aided Molecular Design, Institute of Physiologically Active Compounds, Russian Academy of Science, 142432, Russia, Chernogolovka, Severniy proezd 1 phone: +7 496 52 21867.
authors.forename: Veniamin Yu
authors.initials: VY
authors.lastname: Grigorev
authors.affiliation: Department of Computer-Aided Molecular Design, Institute of Physiologically Active Compounds, Russian Academy of Science, 142432, Russia, Chernogolovka, Severniy proezd 1 phone: +7 496 52 21867.
authors.forename: Olga E
authors.initials: OE
authors.lastname: Raevskaja
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK.
authors.forename: John C
authors.initials: JC
authors.lastname: Dearden
mesh_terms: D003198:Computer Simulation; D008958:Models, Molecular
keywords: Aqueous solubility; Classification/Regression; Global models; Local models; Physicochemical molecular descriptors; QSPR