title: QSAR Models Guided by Molecular Dynamics Applied to Human Glucokinase Activators.
abstract: In this study, quantitative structure-activity relationship studies which make use of molecular dynamics trajectories were performed on a set of 54 glucokinase protein activators. The conformations obtained by molecular dynamics simulation were superimposed according to the twelve alignments tested in a virtual three-dimensional box comprised of 2 Å cells. The models were generated by the technique that combines genetic algorithms and partial least squares. The best alignment models generated with a determination coefficient (r(2)) between 0.674 and 0.743 and cross-validation (q(2)) between 0.509 and 0.610, indicating good predictive capacity. The 4D-QSAR models developed in this study suggest novel molecular regions to be explored in the search for better glucokinase activators.
authors.affiliation: Department of Chemistry, Federal University of Lavras, P.O. Box 3037, Lavras, 37200-000, Brazil.
authors.forename: Tamiris Maria
authors.initials: TM
authors.lastname: de Assis
authors.affiliation: Department of Chemistry, Federal University of Lavras, P.O. Box 3037, Lavras, 37200-000, Brazil.
authors.forename: Giovanna Cardoso
authors.initials: GC
authors.lastname: Gajo
authors.affiliation: Department of Chemistry, Federal University of Lavras, P.O. Box 3037, Lavras, 37200-000, Brazil.
authors.forename: Letícia Cristina
authors.initials: LC
authors.lastname: de Assis
authors.affiliation: Department of Chemistry, Federal University of Lavras, P.O. Box 3037, Lavras, 37200-000, Brazil.
authors.forename: Letícia Santos
authors.initials: LS
authors.lastname: Garcia
authors.affiliation: Department of Chemistry, Federal University of Lavras, P.O. Box 3037, Lavras, 37200-000, Brazil.
authors.forename: Daniela Rodrigues
authors.initials: DR
authors.lastname: Silva
authors.affiliation: Department of Chemistry, Federal University of Lavras, P.O. Box 3037, Lavras, 37200-000, Brazil.|Center for Basic and Applied Research, Faculty of Informatics and Management, University of Hradec Kralove, Hradec Kralove, Czech Republic.
authors.forename: Teodorico Castro
authors.initials: TC
authors.lastname: Ramalho
authors.affiliation: Department of Chemistry, Federal University of Lavras, P.O. Box 3037, Lavras, 37200-000, Brazil.
authors.forename: Elaine Fontes Ferreira
authors.initials: EF
authors.lastname: da Cunha
mesh_terms: D004789:Enzyme Activation; D005941:Glucokinase / Q000378:metabolism*; D006801:Humans; D056004:Molecular Dynamics Simulation; D021281:Quantitative Structure-Activity Relationship
chemical_list: D005941:Glucokinase
keywords: diabetes mellitus; glucokinase; glucokinase activators and 4D-QSAR; type 2 diabetes