title: Structure prediction of the second extracellular loop in G-protein-coupled receptors.
abstract: G-protein-coupled receptors (GPCRs) play key roles in living organisms. Therefore, it is important to determine their functional structures. The second extracellular loop (ECL2) is a functionally important region of GPCRs, which poses significant challenge for computational structure prediction methods. In this work, we evaluated CABS, a well-established protein modeling tool for predicting ECL2 structure in 13 GPCRs. The ECL2s (with between 13 and 34 residues) are predicted in an environment of other extracellular loops being fully flexible and the transmembrane domain fixed in its x-ray conformation. The modeling procedure used theoretical predictions of ECL2 secondary structure and experimental constraints on disulfide bridges. Our approach yielded ensembles of low-energy conformers and the most populated conformers that contained models close to the available x-ray structures. The level of similarity between the predicted models and x-ray structures is comparable to that of other state-of-the-art computational methods. Our results extend other studies by including newly crystallized GPCRs.
authors.affiliation: University of Warsaw, Faculty of Chemistry, Laboratory of Theory of Biopolymers, Pasteura 1, 02-093 Warsaw, Poland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kmiecik
authors.affiliation: University of Warsaw, Faculty of Chemistry, Laboratory of Theory of Biopolymers, Pasteura 1, 02-093 Warsaw, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Jamroz
authors.affiliation: Mossakowski Medical Research Center, Polish Academy of Sciences, Bioinformatics Laboratory, Pawinskiego 5, 02-106 Warsaw, Poland. Electronic address: mkolin@imdik.pan.pl.
authors.forename: Michal
authors.initials: M
authors.lastname: Kolinski
mesh_terms: D000595:Amino Acid Sequence; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry*
chemical_list: D043562:Receptors, G-Protein-Coupled