Modelling G-protein coupled receptors

Computational Modeling Approaches to Structure−Function Analysis of G Protein-Coupled Receptors

“…Because of the lack of a proper homologous template for comparative modeling of GPCRs, various ab initio approaches have been developed for computational modeling of GPCRs (reviewed also in ref ).…”

“…Most of the computational experiments done so far on GPCRs concerned ligand binding site identification and predictions of the ligand interaction modes for either qualitative or quantitative structure affinity/selectivity relationships and drug design (reviewed also in refs and −479). In contrast, very few computational studies have been aimed at investigating the structural changes induced by agonists into receptor portions more or less distal from the ligand binding site. ,,,,,,,,,,,,,, The results of these studies are reviewed in a separate section.…”

“…Thus, all the intermolecular interaction models reported so far were achieved following either manual or automatic docking of the ligand into the putative binding site of the target receptor model. Given the enormous number of reports on the matter, we prefer to broadly classify and quote them according to the approach used to bundle the TM helices, i.e., (a) by ab initio approaches strongly based on the 2D electron density maps of rhodopsin ,,− or on the integration between 2D and 3D electron density maps of rhodopsin and inferences of Baldwin's analysis 60,83,238,240-244,246-248,250,255,258,260,262-267,269-278,280-292, 298-301,303 or (b) by comparative modeling, employing either BRD 160,161,163,165-168,170-190,192-194,197,198,200-202,204,205, 209,210,441,485-491 or ab initio models of rhodopsin, − , or, since very recently, the crystal structure of bovine rhodopsin as a template. ,,,,,,,,,,, 378-394,397,399-411,415-422,424-438,440,441,480,492-503 Alternative approaches consisted of modifying helix-bundle models previously achieved using BRD as a template to incorporate the available structural information on rhodopsin, i.e., the cryo-microscopy 3D map, the outcomes of Baldwin's study, and the crystal structure. ,− ,, A number of computational modeling studies on the GPCR ligand binding sites are also reviewed in refs and −479.…”

Lutropin Receptor Function: Insights from Natural, Engineered, and Computer‐Simulated Mutations

“…3D Model Building of LHR. Until recently, no high resolution structure of a GPCR was available and thus three-dimensional models of GPCRs were generally achieved via ab initio approaches or by using bacteriorhodopsin as a template (27 ). The ab initio approach has been employed for building static (23) and dynamic (24) models of the human LHR.…”

Ligand-Receptor Communication and Drug Design

“…[30,[33][34][35][36][37][38][39][40]). In contrast, very few computational studies have been aimed at investigating the structural changes as induced by agonists into receptor portions more or less distal from the ligand binding site (reviewed in Ref.…”