New insights into the binding mode of melanin concentrating hormone receptor-1 antagonists: homology modeling and explicit membrane molecular dynamics simulation study.

ABSTRACT: Melanin concentrating hormone (MCH) is a cyclic 19-amino-acid peptide expressed mainly in the hypothalamus. It is involved in the control of feeding behavior, energy homeostasis, and body weight. Administration of MCH-R1 antagonists has been proved to reduce food intake and cause weight loss in animal models. In the present study, a homology model of the human MCH-R1 was constructed using the crystal structure of bovine rhodopsin (PDB: 1u19) as a template. Based on the observation that MCH-R1 can bind ligands of high chemical diversity, the initial model was subjected to an extensive ligand-supported refinement using antagonists of different chemotypes. The refinement process involved stepwise energy minimizations and molecular dynamics simulations. The refined model was inserted into a pr

SUBMITTER: Helal MA 

PROVIDER: S-EPMC3090266 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature