Molecular mechanism at the TSH receptor: Modulation of signalling activity via extracellular loop 2

On the Applicability of GPCR Homology Models to Computer-Aided Drug Discovery: A Comparison between In Silico and Crystal Structures of the β2-Adrenergic Receptor

“…Loops of significantly different lengths were modeled de novo without aligning them with those of rhodopsin. Due to the amount of experimental evidence suggesting a role of EL2 in ligand recognition and receptor activation, ,,– two different models of the β 2 -AR were built: model 1 was built aligning the conserved Cys in EL2 and the four adjacent residues that in rhodopsin form a β-strand with the corresponding residues in the β 2 -AR; model 2 was built completely de novo, without any alignment between the sequences of rhodopsin and the β 2 -AR. The models were built with Modeler, , using as a template the crystal structure of rhodopsin published by Schertler and co-workers in 2004 (1gzm) that, among the published rhodopsin structures, is thought to provide a better conformation for the cytoplasmic ends of TM5 and TM6 .…”