title: Molecular modeling studies on the human neuropeptide S receptor and its antagonists.
abstract: Neuropeptide S (NPS) is a 20-residue peptide of great interest due to its potential involvement in several biological processes such as arousal, anxiety, and food intake. The NPS receptor belongs to the rhodopsin-like G-protein-coupled receptor superfamily, and several polymorphisms and isoforms of this receptor are associated with asthma, allergies, and bronchial hyper-responsiveness, in particular the Asn 107 Ile mutation. Limited structural information is available for this peptide-receptor system, particularly regarding the NPS receptor structure, its nonpeptide ligands, and the molecular aspects of agonist and antagonist binding processes. In this work, rhodopsin-based homology models of the NPS receptor and its Asn 107 Ile variant were built and refined in a membrane bilayer model, and binding modes for nonpeptide antagonists were simulated. This study provides the first structural study of the human NPS receptor, and the results provide a starting point for further characterization of the binding modes of its antagonists, and for the rational design of new NPS receptor ligands.
authors.affiliation: Dipartimento di Scienze Chimiche, Università di Camerino, Via S. Agostino 1, 62032 Camerino, MC, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Dal Ben
authors.forename: Ippolito
authors.initials: I
authors.lastname: Antonini
authors.forename: Michela
authors.initials: M
authors.lastname: Buccioni
authors.forename: Catia
authors.initials: C
authors.lastname: Lambertucci
authors.forename: Gabriella
authors.initials: G
authors.lastname: Marucci
authors.forename: Sauro
authors.initials: S
authors.lastname: Vittori
authors.forename: Rosaria
authors.initials: R
authors.lastname: Volpini
authors.forename: Gloria
authors.initials: G
authors.lastname: Cristalli
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D003198:Computer Simulation; D006801:Humans; D008024:Ligands; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D012243:Rhodopsin / Q000737:chemistry; D016415:Sequence Alignment; D040681:Structural Homology, Protein
chemical_list: D008024:Ligands; D008051:Lipid Bilayers; C484532:NPSR1 protein, human; D010879:Piperazines; D043562:Receptors, G-Protein-Coupled; D000077489:Piperazine; D012243:Rhodopsin