title: Predictive Models for Halogen-bond Basicity of Binding Sites of Polyfunctional Molecules.
abstract: Halogen bonding (XB) strength assesses the ability of an electron-enriched group to be involved in complexes with polarizable electrophilic halogenated or diatomic halogen molecules. Here, we report QSPR models of XB of particular relevance for an efficient screening of large sets of compounds. The basicity is described by pKBI2 , the decimal logarithm of the experimental 1 : 1 (B : I2 ) complexation constant K of organic compounds (B) with diiodine (I2 ) as a reference halogen-bond donor in alkanes at 298 K. Modeling involved ISIDA fragment descriptors, using SVM and MLR methods on a set of 598 organic compounds. Developed models were then challenged to make predictions for an external test set of 11 polyfunctional compounds for which unambiguous assignment of the measured effective complexation constant to specific groups out of the putative acceptor sites is not granted. At this stage, developed models were used to predict pKBI2 of all putative acceptor sites, followed by an estimation of the predicted effective complexation constant using the ChemEqui program. The best consensus models perform well both in cross-validation (root mean squared error RMSE=0.39-0.47 logKBI2 units) and external predictions (RMSE=0.49). The SVM models are implemented on our website (http://infochim.u-strasbg.fr/webserv/VSEngine.html) together with the estimation of their applicability domain and an automatic detection of potential halogen-bond acceptor atoms.
authors: Laboratoire de Chémoinformatique, UMR 7140 CNRS, Université de Strasbourg, 1, rue Blaise Pascal, 67000 Strasbourg, France phone: + 33368851560.|Laboratory of Chemoinformatics and Molecular Modeling, Butlierov Institut of Chemistry, Kazan Federal University, Kremlevskaya 18, Kazan, Russia.
authors: Marta
authors: M
authors: Glavatskikh
authors: Laboratory of Chemoinformatics and Molecular Modeling, Butlierov Institut of Chemistry, Kazan Federal University, Kremlevskaya 18, Kazan, Russia.
authors: Timur
authors: T
authors: Madzhidov
authors: Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Leninskiy prospect, 31, 119071, Moscow, Russia.
authors: Vitaly
authors: V
authors: Solov'ev
authors: Laboratoire de Chémoinformatique, UMR 7140 CNRS, Université de Strasbourg, 1, rue Blaise Pascal, 67000 Strasbourg, France phone: + 33368851560.
authors: Gilles
authors: G
authors: Marcou
authors: Laboratoire de Chémoinformatique, UMR 7140 CNRS, Université de Strasbourg, 1, rue Blaise Pascal, 67000 Strasbourg, France phone: + 33368851560.
authors: Dragos
authors: D
authors: Horvath
authors: Chimie et Interdisciplinarité: Synthèse, Analyse, Modélisation (CEISAM), UMR CNRS 6230, Université de Nantes, 2 rue de la Houssinière - BP 92208, 44322 Nantes Cedex 3 (France).
authors: Jérôme
authors: J
authors: Graton
authors: Chimie et Interdisciplinarité: Synthèse, Analyse, Modélisation (CEISAM), UMR CNRS 6230, Université de Nantes, 2 rue de la Houssinière - BP 92208, 44322 Nantes Cedex 3 (France).
authors: Jean-Yves
authors: JY
authors: Le Questel
authors: Laboratoire de Chémoinformatique, UMR 7140 CNRS, Université de Strasbourg, 1, rue Blaise Pascal, 67000 Strasbourg, France phone: + 33368851560. varnek@unistra.fr.|Laboratory of Chemoinformatics and Molecular Modeling, Butlierov Institut of Chemistry, Kazan Federal University, Kremlevskaya 18, Kazan, Russia. varnek@unistra.fr.
authors: Alexandre
authors: A
authors: Varnek
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D006219:Halogens / Q000737:chemistry*; D006860:Hydrogen Bonding; D008956:Models, Chemical; D021281:Quantitative Structure-Activity Relationship
chemical_list: D006219:Halogens
keywords: Halogen bonding; QSPR; applicability domain; ensemble modeling