title: Predictive Models for the Free Energy of Hydrogen Bonded Complexes with Single and Cooperative Hydrogen Bonds.
abstract: In this work, we report QSPR modeling of the free energy ΔG of 1 : 1 hydrogen bond complexes of different H-bond acceptors and donors. The modeling was performed on a large and structurally diverse set of 3373 complexes featuring a single hydrogen bond, for which ΔG was measured at 298 K in CCl4. The models were prepared using Support Vector Machine and Multiple Linear Regression, with ISIDA fragment descriptors. The marked atoms strategy was applied at fragmentation stage, in order to capture the location of H-bond donor and acceptor centers. Different strategies of model validation have been suggested, including the targeted omission of individual H-bond acceptors and donors from the training set, in order to check whether the predictive ability of the model is not limited to the interpolation of H-bond strength between two already encountered partners. Successfully cross-validating individual models were combined into a consensus model, and challenged to predict external test sets of 629 and 12 complexes, in which donor and acceptor formed single and cooperative H-bonds, respectively. In all cases, SVM models outperform MLR. The SVM consensus model performs well both in 3-fold cross-validation (RMSE=1.50 kJ/mol), and on the external test sets containing complexes with single (RMSE=3.20 kJ/mol) and cooperative H-bonds (RMSE=1.63 kJ/mol).
authors.affiliation: Laboratoire de Chémoinformatique, UMR 7140 CNRS, Université de Strasbourg, 1, rue Blaise Pascal, 67000, Strasbourg, France.|Laboratory of Chemoinformatics and Molecular Modeling, Butlerov Institut of Chemistry, Kazan Federal University, Kremlevskaya 18, Kazan, Russia.
authors.forename: Marta
authors.initials: M
authors.lastname: Glavatskikh
authors.affiliation: Laboratory of Chemoinformatics and Molecular Modeling, Butlerov Institut of Chemistry, Kazan Federal University, Kremlevskaya 18, Kazan, Russia.
authors.forename: Timur
authors.initials: T
authors.lastname: Madzhidov
authors.affiliation: A.N. Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Leninskiy prosp., 31, 119071, Moscow, Russia.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Solov'ev
authors.affiliation: Laboratoire de Chémoinformatique, UMR 7140 CNRS, Université de Strasbourg, 1, rue Blaise Pascal, 67000, Strasbourg, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Marcou
authors.affiliation: Laboratoire de Chémoinformatique, UMR 7140 CNRS, Université de Strasbourg, 1, rue Blaise Pascal, 67000, Strasbourg, France.
authors.forename: Dragos
authors.initials: D
authors.lastname: Horvath
authors.affiliation: Laboratoire de Chémoinformatique, UMR 7140 CNRS, Université de Strasbourg, 1, rue Blaise Pascal, 67000, Strasbourg, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Varnek
mesh_terms: D019277:Entropy; D006859:Hydrogen / Q000737:chemistry*; D006860:Hydrogen Bonding; D008956:Models, Chemical; D008958:Models, Molecular; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D006859:Hydrogen
keywords: QSPR; free energies of single and cooperative hydrogen bonds; hydrogen bonding strength