title: QSAR and proteo-chemometric analysis of the interaction of a series of organic compounds with melanocortin receptor subtypes.
abstract: We have created quantitative structure-activity relationship (QSAR) models describing the interaction of a series of 54 organic compounds with four melanocortin (MC) receptor subtypes, MC(1), MC(3), MC(4), and MC(5). In addition to traditional QSAR analysis, we applied our recently developed proteo-chemometrics approach. Proteo-chemometrics is based on the combined analysis of series of receptors and ligands, wherein descriptions of ligands, proteins, and so-called ligand-protein cross-terms are correlated with interaction activities. The compounds were characterized by structural descriptors, including three-dimensional grid-independent descriptors (GRINDs), topological descriptors, and geometrical descriptors. Description of receptors was obtained by computing the receptors' amino acid sequence identities. Both the QSAR and proteo-chemometrics approaches resulted in models with essentially the same statistical significance: the cross-validated correlation coefficient q(2) for the proteo-chemometric model being 0.71, while for the QSAR models the q(2)s were 0.75, 0.68, 0.63, and 0.71 for the MC(1), MC(3)(-)(5) receptor, respectively. However, the proteo-chemometrics modeling provided more detailed information about receptor-ligand interactions and determinants for receptor subtype selectivity than did QSAR.
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Box 591 BMC, SE751 24 Uppsala, Sweden.
authors.forename: Maris
authors.initials: M
authors.lastname: Lapinsh
authors.forename: Peteris
authors.initials: P
authors.lastname: Prusis
authors.forename: Ilze
authors.initials: I
authors.lastname: Mutule
authors.forename: Felikss
authors.initials: F
authors.lastname: Mutulis
authors.forename: Jarl E S
authors.initials: JE
authors.lastname: Wikberg
mesh_terms: D008958:Models, Molecular; D009281:Naphthalenes / Q000737:chemistry; D009930:Organic Chemicals / Q000737:chemistry*; D040901:Proteomics; D021281:Quantitative Structure-Activity Relationship; D018043:Receptors, Corticotropin / Q000737:chemistry*; D044101:Receptors, Melanocortin
chemical_list: D009281:Naphthalenes; D009930:Organic Chemicals; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin