title: Proteochemometrics modeling of the interaction of amine G-protein coupled receptors with a diverse set of ligands.
abstract: We have evaluated the proteochemometrics approach in the analysis of the interactions of a diverse set or organic ligands with subtypes of serotonin, dopamine, histamine, and adrenergic receptors. As used herein, proteochemometrics exploits affinity data for series of organic amines binding to wild-type amine G protein-coupled receptors, correlating it to descriptions and cross-description derived from the primary amino acid sequences of the receptors and the computed structures of the organic compounds. We show that after appropriate data preprocessing, statistically valid models that have good external predictive ability can be created. Evaluation of the models gave important quantitative insight into the mode of interactions of the amine G protein-coupled receptors with their ligands.
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Maris
authors.initials: M
authors.lastname: Lapinsh
authors.forename: Peteris
authors.initials: P
authors.lastname: Prusis
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Lundstedt
authors.forename: Jarl E S
authors.initials: JE
authors.lastname: Wikberg
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D001665:Binding Sites; D016000:Cluster Analysis; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D008956:Models, Chemical; D011941:Receptors, Adrenergic / Q000737:chemistry / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000737:chemistry / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D008024:Ligands; D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin