AUTHOR=Barreto Carlos A. V. , Baptista  Salete J. , Preto António J. , Silvério Daniel , Melo Rita , Moreira Irina S. 

TITLE=Decoding Partner Specificity of Opioid Receptor Family

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2021.715215

DOI=10.3389/fmolb.2021.715215

ISSN=2296-889X

ABSTRACT=<p>This paper describes an exciting big data analysis compiled in a freely available database, which can be applied to characterize the coupling of different G-Protein coupled receptors (GPCRs) families with their intracellular partners. Opioid receptor (OR) family was used as case study in order to gain further insights into the physiological properties of these important drug targets, known to be associated with the opioid crisis, a huge socio-economic issue directly related to drug abuse. An extensive characterization of all members of the ORs family (<italic>μ</italic> (MOR), <italic>δ</italic> (DOR), <italic>κ</italic> (KOR), nociceptin (NOP)) and their corresponding binding partners (ARRs: Arr2, Arr3; G-protein: G<sub>i1</sub>, G<sub>i2</sub>, G<sub>i3</sub>, G<sub>o</sub>, G<sub>ob</sub>, G<sub>z</sub>, G<sub>q</sub>, G<sub>11</sub>, G<sub>14</sub>, G<sub>15</sub>, G<sub>12</sub>, G<sub>ssh</sub>, G<sub>slo</sub>) was carried out. A multi-step approach including models’ construction (multiple sequence alignment, homology modeling), complex assembling (protein complex refinement with HADDOCK and complex equilibration), and protein-protein interface characterization (including both structural and dynamics analysis) were performed. Our database can be easily applied to several GPCR sub-families, to determine the key structural and dynamical determinants involved in GPCR coupling selectivity.</p>