GPCRs are the largest super-family of transmembrane proteins that mediate signaling transduction via a wide range of ligands including ions, small molecules and peptides. Neurotensin (NT), as one of the most important endogenous peptide GPCR ligands, is intrinsically disordered in solution, but must fold into specific conformations to complex with its receptor (NTSR1). This process in not well understood and furthering our knowledge on NT-NTSR1 recognition mechanisms may aid in the development of new drugs for treatment of NT-associated diseases. NT is regarded as a neuromodulator in the central nervous system and as a hormone in gastrointestinal tract. It is also a key player in the pathophysiology of different diseases such as schizophrenia, colon cancer, breast cancer, diabetes mellitus and obesity. Although several crystal structures of NTSR1 have been resolved in complex with neurotensin 8-13, there is a lack of information about how the intrinsically discorded NT peptide takes on an ordered fold upon binding NTSR1. Hence, we are focusing on the significance of coupled folding and binding in interaction of neurotensin with neurotensin receptor. Nuclear magnetic resonance is a powerful technique for the study of protein-ligand interaction and protein dynamics but is challenging to apply to GPCRs because of their instability. Previous work in my lab has established methods to prepare NMR samples of NTSR1, and thus I will use NMR to investigate the possible pathways of interactions that guide the NT into the binding site on NTSR1.