Molecular Modeling Studies on the Human Neuropeptide S Receptor and Its Antagonists

作者：Dal Ben Diego; Antonini Ippolito; Buccioni Michela; Lambertucci Catia; Marucci Gabriella; Vittori Sauro; Volpini Rosaria; Cristalli Gloria^*

来源：ChemMedChem, 2010, 5(3): 371-383.

DOI：10.1002/cmdc.200900467

• binding sites
• membrane proteins
• molecular modeling
• neuropeptide S receptor
• receptor antagonists

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 NIPS 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 hyperresponsiveness, in particular the Asn 107 lle 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 NIPS receptor and its Asn 107 lle 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 NIPS 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.

• 出版日期2010-3