title: 3D-QSAR predictions for α-cyclodextrin binding constants using quantum mechanically based descriptors.
abstract: Binding of organic chemicals to α-cyclodextrin (αCD) is a typical example for host-guest complexation that is influenced by the 3D-structure of both the binding site (host) and the solute (guest). Prediction of the binding constant is challenging and requires a successful representation of the binding site-solute interactions in the 3D-space. In this study, we tested if a 3D quantitative structure activity relationship (3D-QSAR) model with quantum mechanically based local sigma profiles (LSPs) derived from the COSMOsar3D method is capable of predicting αCD binding constants from the most recent literature and how the model performs in comparison to a standard comparative molecular field analysis and to a reference 2D-QSAR. The results showed that the new 3D-QSAR model was more predictive than both reference models (RMSE 0.45 vs 0.53/0.52, R20.70 vs 0.53/0.68). Furthermore, only the new model captured the differences in the binding constants between structural isomers of aliphatic alcohols and allowed an extrapolation of the prediction to another literature data set. The high performance of the 3D-QSAR model with LSPs tested in this study and its theoretical robustness suggest that this modeling approach should be applicable to other binding processes including protein binding.
authors.affiliation: Helmholtz Centre for Environmental Research UFZ, Permoserstr. 15, D-04318 Leipzig, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Linden
authors.affiliation: Helmholtz Centre for Environmental Research UFZ, Permoserstr. 15, D-04318 Leipzig, Germany; University of Halle-Wittenberg, Institute of Chemistry, Kurt Mothes Str. 2, D-06120 Halle, Germany.
authors.forename: Kai-Uwe
authors.initials: KU
authors.lastname: Goss
authors.affiliation: Helmholtz Centre for Environmental Research UFZ, Permoserstr. 15, D-04318 Leipzig, Germany; Osaka City University, Urban Research Plaza & Graduate School of Engineering, Sugimoto 3-3-138, Sumiyoshi-ku, 558-8585 Osaka, Japan. Electronic address: satoshi.endo@urban.eng.osaka-cu.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Endo
mesh_terms: D001665:Binding Sites; D008962:Models, Theoretical; D009930:Organic Chemicals / Q000737:chemistry*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D011789:Quantum Theory; D047391:alpha-Cyclodextrins / Q000737:chemistry*
chemical_list: D009930:Organic Chemicals; D047391:alpha-Cyclodextrins; C032613:alpha-cyclodextrin
keywords: Binding constant; Inclusion complex; Prediction; α-Cyclodextrin (CD)